Heart Disease in Heart Disease in Women Women

A Call to ActionA Call to Action

Jo-Ann Eastwood PhD CCNS ACNP-BCJo-Ann Eastwood PhD CCNS ACNP-BC

Assistant Professor Assistant Professor

UCLA School of NursingUCLA School of Nursing

Nurse ResearcherNurse Researcher

Womanrsquos Heart ProgramWomanrsquos Heart Program

Cedars Sinai Medical CenterCedars Sinai Medical Center

HeartDisease

The leadingkiller ofwomenat allages

Cardiovascular Disease in Cardiovascular Disease in WomenWomen

382 million women (34) are living with 382 million women (34) are living with cardiovascular disease and a much larger cardiovascular disease and a much larger population is at riskpopulation is at risk

Heart disease and stroke are the no 1 and Heart disease and stroke are the no 1 and no 3 killers of women over age 25no 3 killers of women over age 25

1 in 30 die of breast cancer but 1 in 25 die of 1 in 30 die of breast cancer but 1 in 25 die of cardiovascular disease or strokecardiovascular disease or stroke

66000 more women than men die per year of 66000 more women than men die per year of cardiovascular disease represents 54 of cardiovascular disease represents 54 of deaths in women compared to 46 in mendeaths in women compared to 46 in men

AHA Heart Disease and Stroke Statistics 2004 Update and Mosca et al Circulation 2007 115 1481-1501

So how long have we known that So how long have we known that women are just not small menwomen are just not small men

Cardiovascular disease mortality trends for males and Cardiovascular disease mortality trends for males and females females (United States 1979-2004) United States 1979-2004) Source NCHS and NHLBISource NCHS and NHLBI

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Dea

ths

in T

ho

usa

nd

s

Males Females

0

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

HeartDisease

The leadingkiller ofwomenat allages

Cardiovascular Disease in Cardiovascular Disease in WomenWomen

382 million women (34) are living with 382 million women (34) are living with cardiovascular disease and a much larger cardiovascular disease and a much larger population is at riskpopulation is at risk

Heart disease and stroke are the no 1 and Heart disease and stroke are the no 1 and no 3 killers of women over age 25no 3 killers of women over age 25

1 in 30 die of breast cancer but 1 in 25 die of 1 in 30 die of breast cancer but 1 in 25 die of cardiovascular disease or strokecardiovascular disease or stroke

66000 more women than men die per year of 66000 more women than men die per year of cardiovascular disease represents 54 of cardiovascular disease represents 54 of deaths in women compared to 46 in mendeaths in women compared to 46 in men

AHA Heart Disease and Stroke Statistics 2004 Update and Mosca et al Circulation 2007 115 1481-1501

So how long have we known that So how long have we known that women are just not small menwomen are just not small men

Cardiovascular disease mortality trends for males and Cardiovascular disease mortality trends for males and females females (United States 1979-2004) United States 1979-2004) Source NCHS and NHLBISource NCHS and NHLBI

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Dea

ths

in T

ho

usa

nd

s

Males Females

0

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Cardiovascular Disease in Cardiovascular Disease in WomenWomen

382 million women (34) are living with 382 million women (34) are living with cardiovascular disease and a much larger cardiovascular disease and a much larger population is at riskpopulation is at risk

Heart disease and stroke are the no 1 and Heart disease and stroke are the no 1 and no 3 killers of women over age 25no 3 killers of women over age 25

1 in 30 die of breast cancer but 1 in 25 die of 1 in 30 die of breast cancer but 1 in 25 die of cardiovascular disease or strokecardiovascular disease or stroke

66000 more women than men die per year of 66000 more women than men die per year of cardiovascular disease represents 54 of cardiovascular disease represents 54 of deaths in women compared to 46 in mendeaths in women compared to 46 in men

AHA Heart Disease and Stroke Statistics 2004 Update and Mosca et al Circulation 2007 115 1481-1501

So how long have we known that So how long have we known that women are just not small menwomen are just not small men

Cardiovascular disease mortality trends for males and Cardiovascular disease mortality trends for males and females females (United States 1979-2004) United States 1979-2004) Source NCHS and NHLBISource NCHS and NHLBI

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Dea

ths

in T

ho

usa

nd

s

Males Females

0

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

So how long have we known that So how long have we known that women are just not small menwomen are just not small men

Cardiovascular disease mortality trends for males and Cardiovascular disease mortality trends for males and females females (United States 1979-2004) United States 1979-2004) Source NCHS and NHLBISource NCHS and NHLBI

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Dea

ths

in T

ho

usa

nd

s

Males Females

0

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Cardiovascular disease mortality trends for males and Cardiovascular disease mortality trends for males and females females (United States 1979-2004) United States 1979-2004) Source NCHS and NHLBISource NCHS and NHLBI

380

400

420

440

460

480

500

520

79 80 85 90 95 00 04

Years

Dea

ths

in T

ho

usa

nd

s

Males Females

0

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

(United States2004) (United States2004) - Not a true underlying cause - Not a true underlying causeSource NCHS and NHLBI Source NCHS and NHLBI

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

52

17

76 4 14

Coronary HeartDisease

Stroke

HF

High Blood Pressure

Diseases of theArteries

Other

Percentage breakdown of deaths from Percentage breakdown of deaths from cardiovascular diseasescardiovascular diseases

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

CVD runs a very different CVD runs a very different course in womencourse in women

Women develop 10-20 years later than Women develop 10-20 years later than menmen

If present at younger age ndash more malign If present at younger age ndash more malign clinical courseclinical course

DM and HTN have relatively gtrole in DM and HTN have relatively gtrole in women compared to menwomen compared to men

Clinical manifestations of HF as well as Rx Clinical manifestations of HF as well as Rx responses differresponses differ

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

And Most ImportantlyhellipAnd Most Importantlyhellip

Despite technological Despite technological and pharmaceutical and pharmaceutical advances there are advances there are little to no reductions little to no reductions in morbidity and in morbidity and mortality for womenmortality for women

Awareness or the Awareness or the lack there of is a lack there of is a significant problem significant problem

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

WOMENrsquoS HEALTHCARE COST GAPWOMENrsquoS HEALTHCARE COST GAPCVD is the CVD is the mostmost costly and costly and most most preventable preventable disease in women yet we spend the disease in women yet we spend the leasleast on t on

screening and preventionscreening and prevention

0

10

20

30

40

50

60

70

CVD GynCA

Total Costs ($)

Inpatient ($)

Outpatient ($)

OutpatientTotal ()

Billions

$60

Hoerger et al J WHampGender-Based Med 199981077

4 3

38

18

We are missingimportant CVDtreatment opportunities

$13

$2 $3

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Note Hospital discharges include people discharged alive dead and status unknown

Hospital discharges for heart failure by sex(United States 1979-2004) Source NHDS NCHS and NHLBI

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Mortality Rates in WomenMortality Rates in WomenAt Every Age More Women Die From Heart Disease Than From CancerAt Every Age More Women Die From Heart Disease Than From Cancer

National Center for Health Statistics 1999164-167National Center for Health Statistics 1999164-167

Coronary artery diseaseCoronary artery disease

StrokeStroke

Lung cancerLung cancer

Breast cancerBreast cancer

Colon cancerColon cancer

Endometrial cancerEndometrial cancer

Age (years)Age (years)

Mo

rtal

ity

Rat

e p

er 1

000

00M

ort

alit

y R

ate

per

100

000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545ndashndash49 5049 50ndashndash54 5554 55ndashndash59 6059 60ndashndash64 6564 65ndashndash69 7069 70ndashndash74 7574 75ndashndash79 8079 80ndashndash84 85+84 85+

50 of women (1 in 2) will 50 of women (1 in 2) will die from CVD compared die from CVD compared with 4 with 4 (1 in 25) who will die from (1 in 25) who will die from breast cancerbreast cancer

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

410

285

70 5935

461

265

6447 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in ThousandsDeaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimerrsquos DiseaseLeading causes of death for all males and females

(United States 2004) Source NCHS and NHLBI

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Women and Heart DiseaseWomen and Heart DiseaseMaking an ImpactMaking an Impact

10487661048766 AHA National Awareness SurveyAHA National Awareness Survey10487661048766 1997ndash 30 aware heart disease is 1 killer1997ndash 30 aware heart disease is 1 killer10487661048766 2000ndash 342000ndash 3410487661048766 2003ndash 462003ndash 4610487661048766 2008ndash 602008ndash 6010487661048766 Knowledge gap remainsKnowledge gap remains ndash ndash especially in women younger than 45 Hispanic and African American especially in women younger than 45 Hispanic and African American

womenwomen10487661048766 ldquoldquoDisconnectrdquo remains ndash only 13 say heart disease is their own greatest Disconnectrdquo remains ndash only 13 say heart disease is their own greatest

health riskhealth risk

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Coronary Heart Disease Mortality Among YoungCoronary Heart Disease Mortality Among YoungAdults in the US 1980 1980-2002 Adults in the US 1980 1980-2002

(Ford et al JACC2007)(Ford et al JACC2007) 10487661048766

Included women and men aged 35 and older using ICD-9 codes in Included women and men aged 35 and older using ICD-9 codes in US Census dataUS Census data

10487661048766 Mortality from CHD fell 52 in men and 49 in womenMortality from CHD fell 52 in men and 49 in women10487661048766 Improved mortality each decade from 1980s 1990s until the 2000sImproved mortality each decade from 1980s 1990s until the 2000s10487661048766Age analysis demonstrates1048766Age analysis demonstrates1048766 Leveling off of mortality decline in men 35-54 yrs in the 2000sLeveling off of mortality decline in men 35-54 yrs in the 2000s10487661048766 Actual increase in mortality in women 35-54 yrs and specifically Actual increase in mortality in women 35-54 yrs and specifically

among women 35-44 yrs (plt005)among women 35-44 yrs (plt005)

Results are consistent with a UK study (OrsquoFlahrty et al Heart Results are consistent with a UK study (OrsquoFlahrty et al Heart 20071011362007101136

Concomitant with increased use of thrombolysis PCI statins and Concomitant with increased use of thrombolysis PCI statins and anti-thrombotics (ASA) yet adverse nutrition physical activity anti-thrombotics (ASA) yet adverse nutrition physical activity obesity and smoking trendsobesity and smoking trends

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Definitions Definitions Primary PreventionPrimary Prevention Modification of risk factors or Modification of risk factors or

prevention of their development in order to prevention of their development in order to prevent or delay the onset of coronary heart prevent or delay the onset of coronary heart disease (CHD)disease (CHD)

Secondary PreventionSecondary Prevention Initiation of therapy to Initiation of therapy to reduce recurrent CHD events and decrease reduce recurrent CHD events and decrease cardiac mortality in patients with established CHDcardiac mortality in patients with established CHD

Primary-and-a-half PreventionPrimary-and-a-half Prevention As individuals As individuals with subclinical CHD are identified the distinction with subclinical CHD are identified the distinction between primary and secondary prevention between primary and secondary prevention becomes blurredbecomes blurred

Celermajer DS Celermajer DS J Am Coll CardiolJ Am Coll Cardiol 2005451994-1996 2005451994-1996

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

((United States 2004)United States 2004)Source NCHS and NHLBISource NCHS and NHLBI

472 419239

655

399 322

1147

1487

0

50

100

150

200

Coronary HeartDisease

Stroke Lung Cancer Breast Cancer

Pe

r 1

000

00

Po

pu

latio

n

White Females Black Females

Age-adjusted death rates for CHD stroke lungAge-adjusted death rates for CHD stroke lung and breast for white and black femalesand breast for white and black females

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Cost-Efficacy of TreatmentCost-Efficacy of Treatment((Cost-effectiveCost-effective ltlt $50000) $50000)

MammographyMammography11

Age GroupAge Group Costyr of life savedCostyr of life saved 50 to 6950 to 69 $21400$21400

40 to 49 40 to 49 $150000$150000Statin Lipid LoweringStatin Lipid Lowering22

CVD StatusCVD Status Costyr of life savedCostyr of life savedYesYes $8400$8400NoNo $50000$50000

1 Salzmann amp Kerlikowske Ann Intern Med 1997 2 NCEP III ATP 2002

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Heart Disease Risk Differs Heart Disease Risk Differs Between Women and Men Between Women and Men

More women than men will have a second More women than men will have a second heart attack within 6 years after their first heart attack within 6 years after their first heart attackheart attack

Women with diabetes are 3 to 4 times Women with diabetes are 3 to 4 times more likely than men to develop heart more likely than men to develop heart diseasedisease

Diabetes doubles the risk of a second Diabetes doubles the risk of a second heart attack in womenheart attack in women

National Heart Lung and Blood Institute National Heart Lung and Blood Institute The Healthy Heart Handbook for WomenThe Healthy Heart Handbook for Women 2003 2003

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Racial and Ethnic Minority Women Racial and Ethnic Minority Women and Cardiovascular Diseaseand Cardiovascular Disease

African American women experience CVD at the African American women experience CVD at the highest rate in the United Stateshighest rate in the United States

Data on racial and ethnic minorities may Data on racial and ethnic minorities may underestimate disease prevalencemortality underestimate disease prevalencemortality especially in American Indians and Alaskan especially in American Indians and Alaskan NativesNatives

Racial and ethnic minority women have higher Racial and ethnic minority women have higher mortality rates at younger agesmortality rates at younger ages

Issues regarding access to information and Issues regarding access to information and access to care cultural competence of providersaccess to care cultural competence of providers

Mosca L et al Mosca L et al CirculationCirculation 2004109573-579 Epub 2004 Feb 4 2004109573-579 Epub 2004 Feb 4

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Counseling During Counseling During Office VisitsOffice Visits

CDC 1995 NAMCS CDC 1995 NAMCS Morb Mortal Wkly RepMorb Mortal Wkly Rep 19984791-95 19984791-95

MenMen

WomenWomen

Physical activityPhysical activity DietDiet WeightWeightreductionreduction

00

1010

2020

3030

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Hypercholesterolemic Hypercholesterolemic Subjects by SexSubjects by Sex

The Atherosclerosis Risk in Communities Study 1987-1989The Atherosclerosis Risk in Communities Study 1987-1989

44

26

3640

27

33

0

10

20

30

40

50

Males

Females

Awaren = (17484202)

Treatedn = (4461664)

Controlledn = (155446)

Nieto et al Arch Int Med Vol 155Apr101995

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

0

20

40

60

80

100

Utilization of Lipid-Lowering Medications Utilization of Lipid-Lowering Medications at Discharge in Patients with AMI at Discharge in Patients with AMI

National Registry of Myocardial Infarction National Registry of Myocardial Infarction (NRMI) 3(NRMI) 3

Fonarow GC et al Circulation 200110338-44

D

isch

arg

ed

on

Lip

id

Th

era

py

Male (n=83806)

Plt00001Plt00001

Female (n=54195)

Age (Years)

Plt00001Plt00001Plt00001Plt00001

P=NSP=NS

P=NSP=NS

lt55 55ndash64 65ndash74 75ndash84 85+

138001 patients discharged from 1470 US hospitals July 1998 to June 1999138001 patients discharged from 1470 US hospitals July 1998 to June 1999

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Mosca L et al Mosca L et al CirculationCirculation 2004109672-693 2004109672-693

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Say Say ALOHAALOHA to Heart Disease in to Heart Disease in WomenWomen

AA ndash Assess your risk high intermediate or low ndash Assess your risk high intermediate or low LL ndash Lifestyle recommendations are first priority ndash Lifestyle recommendations are first priority OO ndash Other interventions prioritized according to ndash Other interventions prioritized according to

expert panel rating scaleexpert panel rating scale HH ndash Highest priority for therapy is for women at ndash Highest priority for therapy is for women at

highest riskhighest risk AA ndash Avoid medical therapies called Class III ndash Avoid medical therapies called Class III

where evidence is lackingwhere evidence is lacking

Mosca L Circulation 2004

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

AA - - Assessment of CHD RiskAssessment of CHD Risk Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

High RiskHigh Risk Established coronary heart diseaseEstablished coronary heart disease Cerebrovascular diseaseCerebrovascular disease Peripheral arterial diseasePeripheral arterial disease Abdominal aortic aneurysmAbdominal aortic aneurysm End-stage or chronic renal diseaseEnd-stage or chronic renal disease Diabetes mellitusDiabetes mellitus 10-year Framingham global risk gt2010-year Framingham global risk gt20

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Classification of CVD Risk in Women (Mosca et al Circ 2007)Classification of CVD Risk in Women (Mosca et al Circ 2007)

At RiskAt Risk Evidence of subclinical vascular disease (eg coronary calcium)Evidence of subclinical vascular disease (eg coronary calcium) Metabolic SyndromeMetabolic Syndrome Poor exercise capacity on treadmill andor abnormal heart rate Poor exercise capacity on treadmill andor abnormal heart rate

recoveryrecovery gt=1 major risk factor for CVD includinggt=1 major risk factor for CVD including

bull Cigarette smokingCigarette smokingbull Poor dietPoor dietbull Physical inactivityPhysical inactivitybull Obesity (esp central obesity)Obesity (esp central obesity)bull Family history of premature CVD (lt55 male or lt65 female relative)Family history of premature CVD (lt55 male or lt65 female relative)bull HypertensionHypertensionbull DyslipidemiaDyslipidemia

Optimal riskOptimal risk Framingham global risk lt10 and a healthy Framingham global risk lt10 and a healthy lifestyle with no risk factorslifestyle with no risk factors

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Priorities for Prevention in Practice Priorities for Prevention in Practice According to Risk AssessmentAccording to Risk Assessment

High-Risk WomenHigh-Risk Women

(gt20 Risk)(gt20 Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

(10 to 20 Risk)(10 to 20 Risk)

Lower-Risk Lower-Risk WomenWomen

(10 Risk)(10 Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Smoking cessation Phys activitycard Phys activitycard rehabrehab

Diet therapyDiet therapyWeight maintreductWeight maintreductBP controlBP controlCholest controlRxCholest controlRxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmtcontrol of DMMgmtcontrol of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maintreductWeight maintreductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight Weight maintreductmaintreduct

Treat individual Treat individual heart risk factors heart risk factors as indicatedas indicated

Class IIa Class IIa recommendationrecommendation

Treatment for Treatment for depressiondepression

Aspirin therapyAspirin therapy

Class IIb Class IIb recommendationsrecommendations

Omega 3 fatty-acid Omega 3 fatty-acid supplementationsupplementation

Folic acid Folic acid supplementationsupplementation

Mosca L ldquoHeart Disease Mosca L ldquoHeart Disease Prevention in Womenrdquo Prevention in Womenrdquo Circulation 2004Circulation 2004

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

L ndash Lifestyle Change First Line of Defense L ndash Lifestyle Change First Line of Defense Against Heart DiseaseAgainst Heart Disease

The AHA expert panel rated the following as Class I The AHA expert panel rated the following as Class I recommendationsrecommendations Stop cigarette smoking and avoid secondhand tobacco Stop cigarette smoking and avoid secondhand tobacco

smokesmoke Get at least 30 minutes of physical activity most or preferably Get at least 30 minutes of physical activity most or preferably

all days (60-90 minutes for those needing to lose or sustain all days (60-90 minutes for those needing to lose or sustain weight)weight)

Start a risk-reduction or cardiac rehabilitation program if Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event recent acute coronary syndrome or cardiovascular event

Eat a heart-healthy diet (consistent with NCEPATP III TLC)Eat a heart-healthy diet (consistent with NCEPATP III TLC) Maintain healthy weight by balancing caloric intake with Maintain healthy weight by balancing caloric intake with

caloric expenditure to achieve BMI between 185-249 kgmcaloric expenditure to achieve BMI between 185-249 kgm22

Mosca et al Circulation 2004 and 2007

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Essential Components of NCEP Essential Components of NCEP Therapeutic Lifestyle Change (TLC)Therapeutic Lifestyle Change (TLC)

bull Decrease in saturated fats (lt7 of total calories) and trans fatty acids1

bull Increased dietary and supplemental fiber1

ndash High-fiber breakfast cereals supplements and so forth

bull Plant sterols and stanols (2 gd)1

ndash Spreads pills added to yogurt or other foods or combined with aspirin

bull Soy protein2

bull Flavonoids (nuts)3

bull Weight loss1

bull Exercise1

1 Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults JAMA 2001285(19)2486-2497 bull 2 Sacks FM et al American Heart Association Nutrition Committee Circulation 2006113(7)1034-1044 bull 3 Kelly JH Jr and Sabateacute J Br J Nutr 200696(suppl 2)S61-S67

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Aspirin in Primary PreventionAspirin in Primary PreventionEffective Gender DifferencesEffective Gender Differences

Ridker P et alRidker P et al N Engl J Med N Engl J Med 2005 3521293-204 2005 3521293-204

1010 505005050202 0202

BDT 1988BDT 1988

CombinedCombined

PPP 2001PPP 2001

HOT 1998HOT 1998

TPT 1998TPT 1998

PHS 1989PHS 1989

RR of MI Among MenRR of MI Among Men

2020

RR = 068 (054RR = 068 (054ndashndash086)086)PP = 001 = 001

RR of Stroke Among MenRR of Stroke Among Men

RR = 113 (096RR = 113 (096ndashndash133)133)P P = 15= 15

10100202 2020 50500505

HOT 1998HOT 1998

CombinedCombined

WHS 2005WHS 2005

PPP 2001PPP 2001

RR of MI Among WomenRR of MI Among Women

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

RR = 099 (083RR = 099 (083ndashndash119)119)PP = 95 = 95

2020

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1010

RR of Stroke Among WomenRR of Stroke Among Women

505005050202

RR = 081 (069RR = 081 (069ndashndash096)096)P P = 01= 01

0505 1010 2020 5050

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

CHD Events Results of Secondary CHD Events Results of Secondary Prevention Studies in WomenPrevention Studies in Women

PP value for heterogeneity=35 value for heterogeneity=35Walsh et al Walsh et al JAMAJAMA 20042912243-2252 20042912243-2252

0 1 2

Placebo NoPlacebo NoEventsWomenEventsWomen

Intervention NoIntervention NoEventsWomenEventsWomen

RR RR (95 CI)(95 CI)

4S4S 9142091420 6040760407068 (051-068 (051-

091)091)

CARECARE 8029080290 4628646286060 (037-060 (037-

097)097)

LIPIDLIPID 104760104760 9075690756087 (067-087 (067-

113)113)

HPSHPS 28216382821638 23716282371628085 (072-085 (072-

099)099)

Total and Total and summarysummary 55731085573108 43330774333077

080 (071-080 (071-091)091)

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Blood Pressure RegulationBlood Pressure Regulationin Womenin Women

3 of every 4 women with high blood 3 of every 4 women with high blood pressure pressure knowknow they have it they have it

Fewer than Fewer than 1 in 31 in 3 are controlling it are controlling it

All women must take steps to control their All women must take steps to control their high blood pressure high blood pressure

NIH Web site Your guide to lowering high blood pressure issues for womenNIH Web site Your guide to lowering high blood pressure issues for womenAvailable at httpwwwnhlbinihgovhbpissuesissueshtmAvailable at httpwwwnhlbinihgovhbpissuesissueshtm

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

AHA Guidelines for CVD Prevention in AHA Guidelines for CVD Prevention in Women Blood PressureWomen Blood Pressure

Encourage an optimal blood pressure of Encourage an optimal blood pressure of lt12080 mm Hg through lifestyle approacheslt12080 mm Hg through lifestyle approaches (Class I Level B)(Class I Level B)

Pharmacotherapy when BP is Pharmacotherapy when BP is 14090 mm Hg14090 mm Hg

Get BP even lower whenGet BP even lower when Target-organ damageTarget-organ damage Diabetes Diabetes

(Class I Level A)(Class I Level A)

Mosca L et al Mosca L et al J Am Coll CardiolJ Am Coll Cardiol 200443900-921 200443900-921

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Additional Risk of CAD Events in Additional Risk of CAD Events in Later LifeLater Life

Development of gestational diabetes Development of gestational diabetes Development of pregnancy-related HTNDevelopment of pregnancy-related HTN More recent data on preeclampsia and More recent data on preeclampsia and

eclampsiaeclampsia

Clustering of risk factors as she ages Clustering of risk factors as she ages should institute therapeutic lifestyle should institute therapeutic lifestyle changes nowchanges now

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Women Experience Women Experience MenopausehellipMenopausehellip Changes with MenopauseChanges with Menopause LipidsLipids Total-CholesterolTotal-Cholesterol HDL-CholesterolHDL-Cholesterol

Prevalence DifferencesPrevalence Differences HypertensionHypertension Metabolic Syndrome Metabolic Syndrome

Risk Factor Disease or Outcome RiskRisk Factor Disease or Outcome Risk TriglyceridesTriglycerides

Diabetes Mellitus Diabetes Mellitus

Obesity (BMI Obesity (BMI gtgt30)30)

Waist Circumference gt35rdquo Waist Circumference gt35rdquo ObesityObesity ~25 of women - BMI ~25 of women - BMI gtgt30 30 Less leisure-time physical activity Less leisure-time physical activity - - Greater functional decline Greater functional decline --

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

75 of women experience vasomotor symptoms during the transition to menopause

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

BMI and Relative Risk of CHD Over 14 BMI and Relative Risk of CHD Over 14 Years Nursersquos Health StudyYears Nursersquos Health Study

Relative risk of CHD Relative risk of CHD increases for BMI gt increases for BMI gt 23 diabetes risk 23 diabetes risk increases for BMI gt increases for BMI gt 2222

Risk also significantly Risk also significantly increases for weight increases for weight gain after age 18 gain after age 18 years of 5 kg or more years of 5 kg or more

0

05

1

15

2

25

3

35

lt21 21-229 23-249 25-289 gt29

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

National Obesity National Obesity Education Initiative Education Initiative

Treatment AlgorithmTreatment Algorithm

Patient Encounter

Hx of 25 BMI

bullMeasure weight height and waist circumference bullCalculate BMI

Examination

Brief reinforcement educate on weight management

Periodic weight check

Advise to maintain weightaddress other risk factors

Clinician and patient devise goals and treatment strategyfor weight loss andrisk factor control

Assess reasons for failure to lose weight

Maintenance counseling Dietary therapy Behavior therapy Physical activity

Treatment

Assess risk factors

No

Yes

1

2

14

15 13

12

11 1016

3

4 6

5 7

8

9

Yes

No

Yes

No

Hx BMI 25

No

Yes

Yes

No

Does patient want to lose weight

Yes

No

Progress being madegoal

achieved

BMI 25 OR waist circumference

gt 88 cm (F) gt 102 cm (M)

BMI 30 OR

[BMI 25 to 299 OR waist circumference

gt88 cm (F) gt102 cm (M)] AND 2 risk

factors

BMImeasured in past

2 years

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Currently a Population at RiskCurrently a Population at Risk

Younger people are caught up in the Younger people are caught up in the obesity diabetes epidemicobesity diabetes epidemic

Need to impress diet smoking cessation Need to impress diet smoking cessation exercise weight managementexercise weight management

Frustration in treating women No one test Frustration in treating women No one test such as a mammogram to say Yes you such as a mammogram to say Yes you have ithelliphelliphellipor you donrsquothave ithelliphelliphellipor you donrsquot

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

OO ndash Other Major Risk Factor ndash Other Major Risk Factor Interventions with Class I Interventions with Class I Recommendations Recommendations (Mosca et al 2007)(Mosca et al 2007)

Blood pressure Blood pressure LipidsLipids DiabetesDiabetes AspirinAspirin Beta-blockers (all women after MI ACS LV Beta-blockers (all women after MI ACS LV

dysfunction)dysfunction) ACE inhibitors ARBS ndash MI CHF DMACE inhibitors ARBS ndash MI CHF DM Aldosterone blockage ndash post MI with CHF Aldosterone blockage ndash post MI with CHF

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Accumulation of Other Risk Factors Accumulation of Other Risk Factors Compound Effects of Dyslipidemia on Risk Compound Effects of Dyslipidemia on Risk

of CHDof CHD

0

5

10

15

20

25

30

35

40

185 210 235 260 285 310 335

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ adapted from the Framingham Heart Study

CH

D R

isk

Per

100

0 (i

n 6

yea

rs)

Serum Cholesterol (mgdL)

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Statin Trials Therapy Reduces Statin Trials Therapy Reduces Major Coronary Events in WomenMajor Coronary Events in Women

n = number of women enrolled 4S = primarily CHD death and nonfatal MI

CARE = coronary death nonfatal MI angioplasty or bypass surgeryAFCAPSTexCAPS = fatalnonfatal MI unstable angina or sudden cardiac death

Miettinen TA et al Circulation 1997964211-4218Lewis SJ et al J Am Coll Cardiol 199832140-146Downs JR et al JAMA 19982791615-1622

4S (n=827) CARE (n=576) AFCAPSTexCAPS (n=997)

2 Prevention 1 Prevention

-50-45-40-35-30-25-20-15-10-505

10

Major coronary events

-34

-46 -46

P=0012

P=0001

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

When LDL-lowering drug therapy When LDL-lowering drug therapy

is employed in high-risk or is employed in high-risk or

moderately high risk patients moderately high risk patients

intensity of therapy should be intensity of therapy should be

sufficient to achieve a 30ndash40 sufficient to achieve a 30ndash40

reduction in LDL-C levelsreduction in LDL-C levels

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

The apple but not the pear shapeis a health risk for women - which are you

Abdominal Obesity and gender differences

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

AspirinAspirin

Aspirin therapy (75 to 325 mgd) should be used Aspirin therapy (75 to 325 mgd) should be used in high-risk women unless contraindicated or in high-risk women unless contraindicated or intolerated (where clopidogrel should be intolerated (where clopidogrel should be substituted)substituted)

Other at risk or healthy women for those aged Other at risk or healthy women for those aged gt=65 consider aspirin therapy (81 mg daily or gt=65 consider aspirin therapy (81 mg daily or 100 mg every other day) if BP controlled and 100 mg every other day) if BP controlled and benefit for strokeMI prevention is likely to benefit for strokeMI prevention is likely to outweigth GI bleedinghemorrhagic stroke riskoutweigth GI bleedinghemorrhagic stroke risk

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

H H ndash Highest Priority for Therapy is ndash Highest Priority for Therapy is for Women at Highest Riskfor Women at Highest Risk

Those at highest risk who already have pre-Those at highest risk who already have pre-existing CVD diabetes or chronic kidney disease existing CVD diabetes or chronic kidney disease are most likely to benefit from preventive therapy are most likely to benefit from preventive therapy involving the following Class I recommendationsinvolving the following Class I recommendations ACE inhibitor therapy (if coughing subst ARB)ACE inhibitor therapy (if coughing subst ARB) Aspirin therapy (baby aspirin or maximum dose of 162 Aspirin therapy (baby aspirin or maximum dose of 162

mg) unless contraindicatedmg) unless contraindicated Beta-blocker therapy in those with prior MI or current Beta-blocker therapy in those with prior MI or current

anginaangina Statin therapy Statin therapy Niacin or fibrate therapy if low HDL presentNiacin or fibrate therapy if low HDL present Fibrates to lower triglycerides and improve HDLFibrates to lower triglycerides and improve HDL Warfarin in those with atrial fibrillation unless Warfarin in those with atrial fibrillation unless

contradindicatedcontradindicated

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

AA ndash Avoid ldquoClass IIIrdquo Interventions ndash Avoid ldquoClass IIIrdquo Interventions(Not proven useful or effective may be harmful)(Not proven useful or effective may be harmful)

Combined estrogen and progestin therapy and Combined estrogen and progestin therapy and estrogen monotherapy since associated with increased estrogen monotherapy since associated with increased risk of CVDrisk of CVD

Selective estrogen-receptor modulators (SERMs) also Selective estrogen-receptor modulators (SERMs) also not recommendednot recommended

Antioxidant supplements including vigtamin E C and Antioxidant supplements including vigtamin E C and beta-carotene beta-carotene

Folic acid with or without B6 or B12 supplementationFolic acid with or without B6 or B12 supplementation Aspirin for MI prevention in women aged lt65 yearsAspirin for MI prevention in women aged lt65 years

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Vitamins Major Vascular Vitamins Major Vascular EventsEvents

Vascular EventVascular Event

Major coronaryMajor coronary 10631063 10471047

Any strokeAny stroke 511511 518518

RevascularizationRevascularization 10581058 10861086

Any of the aboveAny of the above 2306 2306 (225)(225)

2312 2312 (225)(225)

Heart Protection Study Collaborative Group Lancet 200236023ndash33

Risk Ratio and 95 CIRisk Ratio and 95 CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0404 0606 0808 1010 1212 1414

100 (094ndash106)P gt 09

Vitamins (n = 10269)

Placebo (n = 10267)

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Nuts Soy Phytosterols GarlicNuts Soy Phytosterols Garlic Nursesrsquo Health Study five 1oz servings of nuts per Nursesrsquo Health Study five 1oz servings of nuts per

week associated with 40 lower risk of CHD events week associated with 40 lower risk of CHD events 2-4 servingswk 25 lower risk2-4 servingswk 25 lower risk

Meta analysis of 38 trials of soy protein showed 47g Meta analysis of 38 trials of soy protein showed 47g intake lowered total LDL-C and trigs 9 13 and intake lowered total LDL-C and trigs 9 13 and 11 respectively no effect on HDL-C11 respectively no effect on HDL-C

Phytosterol-supplemented foods (eg stanol ester Phytosterol-supplemented foods (eg stanol ester margarine) lowers LDL-C avg 10margarine) lowers LDL-C avg 10

Meta-analysis of garlic studies showed 9 total Meta-analysis of garlic studies showed 9 total cholesterol reduction from 12-1 clove consumed daily cholesterol reduction from 12-1 clove consumed daily for 6 monthsfor 6 months

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Diabetes as a CHD Risk Diabetes as a CHD Risk EquivalentEquivalent

10-year risk for CHD 10-year risk for CHD 20 20 High mortality with established CHDHigh mortality with established CHD

High mortality with acute MIHigh mortality with acute MI High mortality post acute MIHigh mortality post acute MI

Prevalence has increased over 25 in Prevalence has increased over 25 in past 15 years in California paralleling past 15 years in California paralleling 50 increase in overweightobesity50 increase in overweightobesity

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

The Metabolic SyndromeThe Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA Diabetes Care 199821310-314Pradhan AD et al JAMA 2001286327-334

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

ATP III The Metabolic SyndromeATP III The Metabolic Syndrome

Diagnosis is established when 3 of these risk factors are presentdaggerAbdominal obesity is more highly correlated with metabolic risk factors than is BMI DaggerSome men develop metabolic risk factors when circumference is only marginally new ADA guideline for impaired fasting glucose gt=100 mgdlincreasedExpert Panel on Detection Evaluation and Treatment ofHigh Blood Cholesterol in Adults JAMA 20012852486-2497

lt40 mgdLlt40 mgdLlt50 mgdLlt50 mgdL

MenMenWomenWomen

gt102 cm (gt40 in)gt102 cm (gt40 in)gt88 cm (gt35 in)gt88 cm (gt35 in)

MenMenWomenWomen

100 mgdL100 mgdLFasting glucoseFasting glucose13013085 mm Hg 85 mm Hg or on or on

medsmedsBlood pressureBlood pressure

HDL-CHDL-C150 mgdL150 mgdLTGTG

Abdominal obesityAbdominal obesitydaggerdagger (Waist circumference(Waist circumferenceDaggerDagger))

Defining LevelDefining LevelRisk FactorRisk Factor

copy 2001 Professional Postgraduate Servicesreg

wwwlipidhealthorg

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Recommendations for Noninvasive Recommendations for Noninvasive ScreeningScreening

AHA Prevention V (Greenland et al Circ 2000) AHA Prevention V (Greenland et al Circ 2000) indicated persons at intermediate risk may be indicated persons at intermediate risk may be suitable for screening by noninvasive tests suitable for screening by noninvasive tests including ABI and carotid US for those over age including ABI and carotid US for those over age 50 years and coronary calcium screening50 years and coronary calcium screening

ATP III has suggested CAC scores above 75ATP III has suggested CAC scores above 75 thth percentile indications for more aggressive percentile indications for more aggressive treatment (eg as CHD risk equivalent)treatment (eg as CHD risk equivalent)

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Cardiovascular Health Study Cardiovascular Health Study Combined intimal-medial thickness Combined intimal-medial thickness

predicts total MI and strokepredicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+) MI or stroke rate 25 over 7 years in those at highest quintile of combined IMT (OrsquoLeary et al 1999)

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Significant Coronary Artery Significant Coronary Artery Calcium (Score gt400)Calcium (Score gt400)

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Risk of Total Mortality by Calcium Category in 10377 Asymptomatic IndividualsShaw LJ et al Radiology 2003 228 826-33

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

No insurance policyNo insurance policy

People get a false sense of security with People get a false sense of security with 0-low CA scores 0-low CA scores

Those without coronary calcium can have Those without coronary calcium can have eventsevents

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Looking Forward Assessing Looking Forward Assessing DiseaseDisease

A good risk assessment is keyA good risk assessment is key Traditional diagnostic testing is not always Traditional diagnostic testing is not always

optimum in womenoptimum in women Many women have more inward Many women have more inward

remodeling of the arteriesremodeling of the arteries Men have more ldquolumpy bumpyrdquo diseaseMen have more ldquolumpy bumpyrdquo disease

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

SymptomsSymptoms in Women with in Women with MIMI Chest pain can present as pressure or tightness but can Chest pain can present as pressure or tightness but can

alsoalso Back painBack pain Abdominal painAbdominal pain Jaw painJaw pain

Other symptomsOther symptoms DyspneaDyspnea NauseaNausea VomitingVomiting SweatingSweating Excessive fatigue (prodromal symptoms up to a month prior to Excessive fatigue (prodromal symptoms up to a month prior to

event) event) McSweeney J 1999 2002McSweeney J 1999 2002

Half of women with MI have no priorchest pain symptoms

Evaluate all symptoms aboveThe waist for cardiac etiologyFIRST

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Women have smaller coronary Women have smaller coronary arteriesarteries

After correcting for After correcting for body surface area body surface area womensrsquo arteries are womensrsquo arteries are smallersmaller

This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter StenosisStenosis Endothelial Endothelial

dysfunctiondysfunction

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Endo-thelium

Smallerarteries

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Plaque Erosion and Outward Plaque Erosion and Outward (Positive) Remodeling(Positive) Remodeling

Plaque erosion and Plaque erosion and thrombus formation thrombus formation 2x likely in women 2x likely in women (men have more (men have more plaque rupture)plaque rupture)

Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward protrudes outward than impinging on the than impinging on the lumenlumen

Adapted from Bellasi et al New insights into ischemic heart disease in women cleveland clinic journal of medicine 74 585-594

Thrombus Formation

Lumen

Plaqueerosion

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Women suffer more plaqueerosions (above) comparedto plaque explosions in men (below) leading to more acute coronary syndromes(unstable angina) and non-Q MI in womenmaking diagnosis more difficult and leading to delays in treatment

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

NIH-NHLBI-sponsored Womenrsquos Ischemia NIH-NHLBI-sponsored Womenrsquos Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

About 50 of women sent home with ldquonormal About 50 of women sent home with ldquonormal coronariesrdquo continue to experience disabling coronariesrdquo continue to experience disabling symptomssymptoms

Possibly dt coronary microvascular or Possibly dt coronary microvascular or macrovascular endothelial dysfunctionmacrovascular endothelial dysfunction

673936 enrolled in WISE had PChP-673936 enrolled in WISE had PChP- PChP-w no obstructive disease is not a benign PChP-w no obstructive disease is not a benign

conditioncondition 2x the number of CV events (MIs strokesCHF 2x the number of CV events (MIs strokesCHF

and CV deaths) than those wo PChPand CV deaths) than those wo PChP JohnsonD etal EurHeart Journal 2006JohnsonD etal EurHeart Journal 2006

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Assessing Ischemic DiseaseAssessing Ischemic Disease

Stress EKG may be less useful in looking for Stress EKG may be less useful in looking for ischemiaischemia Guidelines still support for women with normal resting Guidelines still support for women with normal resting

12 lead EKG12 lead EKG Decreased functional capacity may predict poor Decreased functional capacity may predict poor

outcomesoutcomes WISE showed that women who could not achieve 47 WISE showed that women who could not achieve 47

METS of work had a risk of death or nonfatal MI 37x METS of work had a risk of death or nonfatal MI 37x higher that others with better functional capacityhigher that others with better functional capacity

Stress ECHO and SPECT are good options in Stress ECHO and SPECT are good options in womenwomen

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

And What about HRTAnd What about HRT

Confusion Confusion

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Heart and EstrogenProgestin Replacement Study Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women(HERS) Secondary Prevention of CHD in Women

Randomized placebo-controlled trial of EP Randomized placebo-controlled trial of EP therapy vs placebo in 2763 women with therapy vs placebo in 2763 women with CHD average age CHD average age 6767 years years

Treatment was 0625 mg CEE + 25 mg Treatment was 0625 mg CEE + 25 mg medroxyprogesterone daily for 4 yearsmedroxyprogesterone daily for 4 years

Primary endpoint nonfatal MI and CHD Primary endpoint nonfatal MI and CHD deathdeath

Secondary endpoints CABG PTCA Secondary endpoints CABG PTCA unstable angina CHF PVD TIAunstable angina CHF PVD TIA

JAMA 1998280605-613

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

JAMA 1998280605-613

HERS ResultsHERS Results

No statistically significant difference between HRT No statistically significant difference between HRT and placebo in both primary and secondary endpoints and placebo in both primary and secondary endpoints after 4 yearsafter 4 years

Within first year Within first year greater incidence in CHD events in HRTgreater incidence in CHD events in HRT group In years group In years 3 and 4 lower CHD events3 and 4 lower CHD events in in HRT group compared to placeboHRT group compared to placebo

HRT lowered LDL 11 and increased HDL 10 HRT lowered LDL 11 and increased HDL 10 compared to placebocompared to placebo

Approximately 50 of randomized women were on lipid-Approximately 50 of randomized women were on lipid-lowering drugslowering drugs

Higher incidence of VTE and cholelithiasis in HRT groupHigher incidence of VTE and cholelithiasis in HRT group

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

More Bad News The Womenrsquos More Bad News The Womenrsquos Health InitiativeHealth Initiative

Over 160000 women nationwide aged 50-79 Over 160000 women nationwide aged 50-79 and postmenopausal have participated in and postmenopausal have participated in various components (observational dietary various components (observational dietary modification and HRT clinical trials) modification and HRT clinical trials)

The EstrogenProgestin component of the HRT The EstrogenProgestin component of the HRT clinical trial involving 16608 women nationwide clinical trial involving 16608 women nationwide was discontinued prematurely in Spring 2002 was discontinued prematurely in Spring 2002 after 52 years of follow-up (instead of 85 after 52 years of follow-up (instead of 85 years)years)

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Does Hormone Replacement Does Hormone Replacement Therapy Prevent Heart DiseaseTherapy Prevent Heart Disease

Meta-Analysis of randomized trials show a Meta-Analysis of randomized trials show a 40 reduction in total mortality w HRT vs 40 reduction in total mortality w HRT vs placebo or no treatment but only when placebo or no treatment but only when women were lt60 yrs baseline women were lt60 yrs baseline

July 2004 Journal of General Internal Medicine July 2004 Journal of General Internal Medicine

Nursesrsquo Health Study showed those on Nursesrsquo Health Study showed those on estrogenprogestin to have approximately estrogenprogestin to have approximately a 60 lower risk of heart disease eventsa 60 lower risk of heart disease events

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

WHI EstrogenProgestin and Estrogen Only WHI EstrogenProgestin and Estrogen Only ResultsResults

Those randomized to estrogenprogestin compared to Those randomized to estrogenprogestin compared to placebo and statistically significant increased risksplacebo and statistically significant increased risks Breast cancer 26 (810000 person years)Breast cancer 26 (810000 person years) Total coronary heart disease 29 (710000 person years)Total coronary heart disease 29 (710000 person years) Stroke 41 (810000 person years)Stroke 41 (810000 person years) Pulmonary embolism 21 X (810000 person years)Pulmonary embolism 21 X (810000 person years) Protective Protective for colorectal cancer (37 lower) and hip for colorectal cancer (37 lower) and hip

fracture (34 lower) no effect endometrial cancer or total fracture (34 lower) no effect endometrial cancer or total mortalitymortality

JAMA 2002 Jul 17288(3)321-33JAMA 2002 Jul 17288(3)321-33 Estrogen-only arm was discontinued in December 2003 and Estrogen-only arm was discontinued in December 2003 and

was associated with a 39 increased risk of stroke (12 was associated with a 39 increased risk of stroke (12 excess strokes per 10000 person years) and 12 significant excess strokes per 10000 person years) and 12 significant increased risk of cardiovascular events increased risk of cardiovascular events JAMA 2004 Apr 14291(14)1701-12 JAMA 2004 Apr 14291(14)1701-12

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

Women Making a ChangeWomen Making a Change

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80

• Heart Disease in Women A Call to Action
• Cardiovascular Disease in Women
• Slide 38
• National Obesity Education Initiative Treatment Algorithm
• O ndash Other Major Risk Factor Interventions with Class I Recommendations (Mosca et al 2007)
• Slide 47
• H ndash Highest Priority for Therapy is for Women at Highest Risk
• A ndash Avoid ldquoClass IIIrdquo Interventions (Not proven useful or effective may be harmful)
• Vitamins Major Vascular Events
• Nuts Soy Phytosterols Garlic
• Recommendations for Noninvasive Screening
• Slide 58
• Cardiovascular Health Study Combined intimal-medial thickness predicts total MI and stroke
• Significant Coronary Artery Calcium (Score gt400)
• Slide 61
• Heart and EstrogenProgestin Replacement Study (HERS) Secondary Prevention of CHD in Women
• HERS Results
• More Bad News The Womenrsquos Health Initiative
• Does Hormone Replacement Therapy Prevent Heart Disease
• WHI EstrogenProgestin and Estrogen Only Results
• Slide 78
• Slide 80