Heart Disease in Women: New Concepts in Prevention

and Management

Nathan D. Wong, PhD, FACC

Professor and Director

Heart Disease Prevention Program

Division of Cardiology

University of California, Irvine

HeartDisease

The leadingkiller ofwomenat allages

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

Cardiovascular Disease in WomenCardiovascular Disease in Women

• 38.2 million women (34%) are living with 38.2 million women (34%) are living with cardiovascular disease and a much larger cardiovascular disease and a much larger population is at risk.population is at risk.

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

• 1 in 30 die of breast cancer, but 1 in 2.5 die of 1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke.cardiovascular disease or stroke.

• 66,000 more women than men die per year of 66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths cardiovascular disease; represents 54% of deaths in women compared to 46% in men.in women compared to 46% in men.

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

CHD: Differences in Presentation and Findings in Women Compared to Men–Lower prevalence of MI–More severe CHF–More severe angina–Less angiographic CAD–More ostial lesions–More microvascular dysfunction?–Abnormal vasomotor tone?–More endothelial dysfunction?

Source: Jacobs 2003

Diagnosis of Coronary Artery Disease in Women

• Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men

• Other Presenting Symptoms– Upper abdominal pain, fullness, burning sensation– Shortness of breath– Nausea– Neck, back, jaw pain

• Associations– Precipitated by exertion– Precipitated by emotional distress

Source: Charney 2002, Goldberg 1998

Women have smaller coronary Women have smaller coronary arteriesarteries

• After correcting for After correcting for body surface area, body surface area, womens’ arteries are womens’ arteries are smallersmaller

• This can seriously This can seriously affect symptoms from affect symptoms from anything that reduces anything that reduces diameterdiameter– StenosisStenosis– Endothelial dysfunctionEndothelial dysfunction

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

• Outward (positive) Outward (positive) remodeling- remodeling- atherosclerotic lesion atherosclerotic lesion protrudes outward than protrudes outward than impinging on the lumenimpinging on the lumen

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 women,making diagnosis more difficult and leading to delays in treatment.

Gender Differences in Atherosclerosis

NEJM 1999

NIH-NHLBI-sponsored Women’s Ischemia NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation WISESyndrome Evaluation WISE

• About 50% of women sent home with “normal About 50% of women sent home with “normal coronaries” continue to experience disabling coronaries” continue to experience disabling symptomssymptoms

• Possibly d/t coronary microvascular or macrovascular Possibly d/t coronary microvascular or macrovascular endothelial dysfunctionendothelial dysfunction

• 673/936 enrolled in WISE had persistent chest pain 673/936 enrolled in WISE had persistent chest pain (PChP)(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, strokes,CHF and 2x the number of CV events (MIs, strokes,CHF and

CV deaths) than those w/o PChP.CV deaths) than those w/o PChP.– Johnson,D, etal EurHeart Journal 2006Johnson,D, 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 4.7 WISE showed that women who could not achieve 4.7

METS of work had a risk of death or nonfatal MI 3.7x METS of work had a risk of death or nonfatal MI 3.7x 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

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. 1999:164-167.National Center for Health Statistics. 1999:164-167.

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

00,0

00M

ort

alit

y R

ate

per

100

,000

65006500

45004500

25002500

16001600

12001200

800800

400400

004545––49 5049 50––54 5554 55––59 6059 60––64 6564 65––69 7069 70––74 7574 75––79 8079 80––84 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

Women Experience Women Experience Menopause…..Menopause…..• 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 >>30)***30)***

Waist Circumference >35” Waist Circumference >35” – ******ObesityObesity ~25% of women - BMI ~25% of women - BMI >>30, 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

Menopause and Menopause and the Risk of Coronary Heart Disease the Risk of Coronary Heart Disease

(modified data from “Menopausal status as a risk for coronary artery disease”(modified data from “Menopausal status as a risk for coronary artery disease”Arch Intern Med 1995;155:57-61Arch Intern Med 1995;155:57-61

0

0.5

1

1.5

2

2.5

3

3.5

4

40 - 45 45 - 49 50 - 54

Before menopauseAfter menopause

Age (in years)

An

nu

al O

ccu

ren

ce o

f H

eart

Att

ack

/100

0

Chest pain or AnginaChest pain or AnginaTypical Angina:Typical Angina: heaviness, pressure or squeezing sensation behind the breastboneheaviness, pressure or squeezing sensation behind the breastbone with with

radiation across the chest, up the neck or down the left armradiation across the chest, up the neck or down the left arm or “strangling” or “suffocating” sensation. or “strangling” or “suffocating” sensation.

caused or worsened by exercise and eased by restcaused or worsened by exercise and eased by rest usually lasts two to five minutesusually lasts two to five minutes

Atypical AnginaAtypical Angina (frequently encountered in women):(frequently encountered in women):shortness of breathshortness of breathextreme fatigueextreme fatiguelightheadedness or faintinglightheadedness or faintingnausea and/or indigestionnausea and/or indigestion

Women’s Early Warning Signs of a Women’s Early Warning Signs of a Heart Attack Heart Attack

• Weeks before Heart Attack (95% of women)Weeks before Heart Attack (95% of women) Unusual fatigue (70.7%)Unusual fatigue (70.7%) Sleep disturbance (47.8%)Sleep disturbance (47.8%) Shortness of breath (42.1%)Shortness of breath (42.1%) Indigestion (39.4%)Indigestion (39.4%) Chest pain (29.7 %)Chest pain (29.7 %)

• At time of Heart AttackAt time of Heart Attack Shortness of breath (57.9%)Shortness of breath (57.9%) Weakness (54.8%)Weakness (54.8%) Fatigue (42.9%)Fatigue (42.9%) Chest pain (57%)Chest pain (57%)

McSweeney, JC et al. Circulation 2003; 2619-2623

Tracking women's awareness of heart disease: an American Heart Association national study

Mosca L, et al. Circulation. 2004 Feb 10;109(5):573-9 • Telephone survey of a nationally representative

random sample of women; 1024 respondents age > or =25 years

• 46% identified heart disease as the leading cause of death in women, up from 30% in 1997 and 34% in 2000

• Black, Hispanic, and younger women (<45 years old) had lower awareness of heart disease

• Only 38% of women reported that their doctors had ever discussed heart disease with them.

Major Risk Factors

• Cigarette smoking (passive smoking?)• Elevated total or LDL-cholesterol• Hypertension (BP 140/90 mmHg or on

antihypertensive medication)• Low HDL cholesterol (<40 mg/dL)† • Family history of premature CHD

– CHD in male first degree relative <55 years– CHD in female first degree relative <65 years

• Age (men 45 years; women 55 years)† HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its

presence removes one risk factor from the total count.

Other Recognized Risk Factors• Obesity: Body Mass Index (BMI)

– Weight (kg)/height (m2)– Weight (lb)/height (in2) x 703

• Obesity BMI >30 kg/m2 with overweight defined as 25-<30 kg/m 2

• Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women

• Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week

BMI and Relative Risk of CHD Over 14 Years: Nurse’s Health Study

• Relative risk of CHD increases for BMI > 23, diabetes risk increases for BMI > 22.

• Risk also significantly increases for weight gain after age 18 years of 5 kg or more. 0

0.5

1

1.5

2

2.5

3

3.5

<21 21-22.9 23-24.9 25-28.9 >29

Diabetes as a CHD Risk Equivalent

• 10-year risk for CHD 20%• High mortality with established CHD

– High mortality with acute MI– High mortality post acute MI

Prevalence has increased over 25% in past 15 years in California, paralleling 50% increase in overweight/obesity

Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients,

With and Without Prior MI

Kaplan-Meier estimatesHaffner SM et al. N Engl J Med 1998;339:229–234

0 1 2 3 4 5 6 7 80

20

40

60

80

100

Nondiabetic subjects without prior MI

Diabetic subjects without prior MI

Nondiabetic subjects with prior MI

Diabetic subjects with prior MI

Years

Surv

ival (%

)

Framingham Heart Study 30-Year Follow-Up:CVD Events in Patients With Diabetes

(Ages 35-64)10

9

20

11

9 63819

3*

30

0

2

4

6

8

10

Age-adjusted annual rate/1,000

Men Women

Total CVD

CHD Cardiac failure

Intermittent claudication

Stroke

Riskratio

P<0.001 for all values except *P<0.05.

Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease.Ruderman N et al, eds. Oxford; 1992.

Adapted from Ballantyne CM. Am J Cardiol. 1998;82:3Q-12Q.

Primary and Secondary Prevention Trials With Statins

2° prevention placebo

2° prevention statin

1° prevention placebo

1° prevention statin

0

5

10

15

20

25

30

80 90 100 110 120 130 140 150 160 170 180 190 200

LDL-C Achieved (mg/dL)

AFCAPS

AFCAPS

WOSCOPS

WOSCOPS

CARECARE

LIPID LIPID

4S

4S

Eve

nt

Rat

e (%

)

HPSHPS

CHD Events: Results of Secondary Prevention CHD Events: Results of Secondary Prevention Studies in WomenStudies in Women

PP value for heterogeneity=.35 value for heterogeneity=.35Walsh et al. Walsh et al. JAMAJAMA. 2004;291:2243-2252.. 2004;291:2243-2252.

0 1 2

Placebo No.Placebo No.Events/WomenEvents/Women

Intervention No.Intervention No.Events/WomenEvents/Women

RR RR (95% CI)(95% CI)

4S4S 91/42091/420 60/40760/4070.68 (0.51-0.68 (0.51-

0.91)0.91)

CARECARE 80/29080/290 46/28646/2860.60 (0.37-0.60 (0.37-

0.97)0.97)

LIPIDLIPID 104/760104/760 90/75690/7560.87 (0.67-0.87 (0.67-

1.13)1.13)

HPSHPS 282/1638282/1638 237/1628237/16280.85 (0.72-0.85 (0.72-

0.99)0.99)

Total and Total and summarysummary 557/3108557/3108 433/3077433/3077

0.80 (0.71-0.80 (0.71-0.91)0.91)

Testing for Ischemic Heart Diseasein Women and Factors to Consider

Technique Assessment Issues in Women

Angiography Coronary anatomy

Less focal disease

Coronary CT Coronary calcification

Less well-validated than other techniques

Echocardiography

Regional wall motion

Reader expertise variable

Nuclear Cardiology

Regional blood flow

Attenuation issues

Source: Charney 2002, Greenland 2007

Drawbacks of Diagnostic Imaging in Women

• Low exercise capacity – likelihood of reaching adequate pressure rate product– Solution: Pharmacologic stress testing

• Breast attenuation artifact – higher false positive imaging studies– Solution: Gated acquisition; attenuation correction for nuclear

imaging– Solution: Echocardiography

• Lower pretest probability of CAD – higher false positive rate– Solution: Integrate clinical variables, risk factors, into

decision-making process

Source: Duvernoy, personal communication

Women and CHD: What Test to Order When

• For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging

• For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging

• In high risk women with typical symptoms of coronary artery disease, consider referral to a cardiologist

• For high risk women, consider cardiac catheterization if symptoms persist despite negative non-invasive imaging

Source: Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005

Women and CHD: What Test to Order When

• A stepwise approach beginning with conventional exercise testing may be considered for women who:– Are at low or intermediate risk for coronary artery disease– Are able to exercise– Have an electrocardiogram that can

be interpreted during stress testing• An image-enhanced test may be more predictive in women than

conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD

Source: Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005

Mosca L et al. Mosca L et al. CirculationCirculation. 2004;109:672-693 and Circulation 2007; 115: 1481-1501.. 2004;109:672-693 and Circulation 2007; 115: 1481-1501.

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

• AA – Assess your risk: high, intermediate, or low? – Assess your risk: high, intermediate, or low?

• LL – Lifestyle recommendations are first priority – Lifestyle recommendations are first priority

• OO – Other interventions prioritized according to – Other interventions prioritized according to expert panel rating scaleexpert panel rating scale

• HH – Highest priority for therapy is for women at – Highest priority for therapy is for women at highest riskhighest risk

• AA – Avoid medical therapies called Class III – Avoid medical therapies called Class III where evidence is lackingwhere evidence is lacking

Mosca L. Circulation 2004

A - Assessment of CHD RiskFor persons without known CHD, other forms of

atherosclerotic disease, or diabetes:• Count the number of risk factors.• Use Framingham scoring if 2 risk factors* to determine the

absolute 10-year CHD risk.• Determine risk status: high (>20% 10-year risk or CHD risk

equivalents), intermediate (10-20% 10-year risk), or low (<10% risk)

*For persons with 0–1 risk factor, Framingham calculations are not necessary.

Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. © 2001, Professional Postgraduate Services®

www.lipidhealth.org

Point Total 10-Year Risk Point Total 10-Year Risk

<9 <1% 2011%

9 1% 2114%

10 1% 2217%

11 1% 2322%

12 1% 2427%

13 2% 25 30%

14 2%15 3%16 4%17 5%18 6%19 8%

Assessing CHD Risk in Women

Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

Step 1: Age

YearsPoints

20-34 -735-39 -340-44 045-49 350-54 655-59 860-64 1065-69 1270-74 1475-79 16

TC Points at Points at Points at Points atPoints at(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69

Age 70-79 <160 0 0 0 0

0160-199 4 3 2 1

1200-239 8 6 4 2

1240-279 11 8 5 3

2280 13 10 7 4

2

HDL-C(mg/dL) Points

60 -1

50-59 0

40-49 1

<40 2

Step 3: HDL-Cholesterol

Systolic BP PointsPoints

(mm Hg) if Untreated if Treated

<120 0 0120-129 1 3130-139 2 4140-159 3 5160 4 6

Step 4: Systolic Blood Pressure

Step 5: Smoking StatusNonsmoker 0 0 0 0

0Smoker 9 7 4 2

1

Age

Total cholesterol

HDL-cholesterol

Systolic blood pressure

Smoking status

Point total

Step 6: Adding Up the Points

Step 7: CHD Risk

Step 2: Total Cholesterol

ATP III Framingham Risk Scoring

© 2001, Professional Postgraduate Services®

www.lipidhealth.org

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 Risk:High 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 >20%10-year Framingham global risk >20%

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 (e.g., coronary calcium)Evidence of subclinical vascular disease (e.g., coronary calcium)– Metabolic SyndromeMetabolic Syndrome– Poor exercise capacity on treadmill and/or abnormal heart rate recoveryPoor exercise capacity on treadmill and/or abnormal heart rate recovery– >=1 major risk factor for CVD including:>=1 major risk factor for CVD including:

• Cigarette smokingCigarette smoking• Poor dietPoor diet• Physical inactivityPhysical inactivity• Obesity (esp central obesity)Obesity (esp central obesity)• Family history of premature CVD (<55 male or <65 female relative)Family history of premature CVD (<55 male or <65 female relative)• HypertensionHypertension• DyslipidemiaDyslipidemia

• Optimal risk:Optimal risk: Framingham global risk <10% and a healthy Framingham global risk <10% and a healthy lifestyle with no risk factorslifestyle with no risk factors

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

High-Risk WomenHigh-Risk Women

(>20% Risk)(>20% Risk)

Intermediate-Risk Intermediate-Risk WomenWomen

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

Lower-Risk WomenLower-Risk Women

(10% Risk)(10% Risk)

Class I Class I recommendationsrecommendations

Smoking cessation Phys Smoking cessation Phys activity/card rehabactivity/card rehab

Diet therapyDiet therapyWeight maint/reductWeight maint/reductBP controlBP controlCholest control/RxCholest control/RxAspirin therapyAspirin therapy

-Blocker therapy-Blocker therapy

ACE inhibitor (ARBs)ACE inhibitor (ARBs)

Mgmt/control of DMMgmt/control of DM

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy dietHeart-healthy dietWeight maint/reductWeight maint/reductBP controlBP control

Cholesterol controlCholesterol control

Smoking cessationSmoking cessation

Physical activityPhysical activity

Heart-healthy diet Heart-healthy diet Weight maint/reductWeight maint/reduct

Treat individual Treat individual heart risk factors as heart risk factors as indicatedindicated

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 “Heart Disease Mosca, L “Heart Disease Prevention in Women” Prevention in Women” Circulation, 2004Circulation, 2004

L – Lifestyle Change: First Line of Defense L – 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 recommendations:recommendations:

– Stop cigarette smoking and avoid secondhand tobacco smokeStop cigarette smoking and avoid secondhand tobacco smoke

– Get at least 30 minutes of physical activity most or preferably all Get at least 30 minutes of physical activity most or preferably all days (60-90 minutes for those needing to lose or sustain weight)days (60-90 minutes for those needing to lose or sustain weight)

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

– Eat a heart-healthy diet (consistent with NCEP/ATP III TLC)Eat a heart-healthy diet (consistent with NCEP/ATP III TLC)

– Maintain healthy weight by balancing caloric intake with caloric Maintain healthy weight by balancing caloric intake with caloric expenditure to achieve BMI between 18.5-24.9 kg/mexpenditure to achieve BMI between 18.5-24.9 kg/m22

Mosca et al. Circulation 2004 and 2007

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

• Decrease in saturated fats (<7% of total calories) and trans fatty acids1

• Increased dietary and supplemental fiber1

– High-fiber breakfast cereals, supplements, and so forth

• Plant sterols and stanols (2 g/d)1

– Spreads, pills, added to yogurt or other foods, or combined with aspirin

• Soy protein2

• Flavonoids (nuts)3

• Weight loss1

• Exercise1

1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285(19):2486-2497. • 2. Sacks FM, et al; American Heart Association Nutrition Committee. Circulation. 2006;113(7):1034-1044. • 3. Kelly JH Jr and Sabaté J. Br J Nutr. 2006;96(suppl 2):S61-S67.

Aspirin in Primary Prevention:Aspirin in Primary Prevention:Effective Gender DifferencesEffective Gender Differences

Ridker, P. et al.,Ridker, P. et al., N Engl J Med N Engl J Med 2005; 352:1293-204. 2005; 352:1293-204.

1.01.0 5.05.00.50.50.20.2 0.20.2

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

2.02.0

RR = 0.68 (0.54RR = 0.68 (0.54––0.86)0.86)PP = .001 = .001

RR of Stroke Among MenRR of Stroke Among Men

RR = 1.13 (0.96RR = 1.13 (0.96––1.33)1.33)P P = .15= .15

1.01.00.20.2 2.02.0 5.05.00.50.5

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 = 0.99 (0.83RR = 0.99 (0.83––1.19)1.19)PP = .95 = .95

2.02.0

Aspirin BetterAspirin Better Placebo BetterPlacebo Better

1.01.0

RR of Stroke Among WomenRR of Stroke Among Women

5.05.00.50.50.20.2

RR = 0.81 (0.69RR = 0.81 (0.69––0.96)0.96)P P = .01= .01

0.50.5 1.01.0 2.02.0 5.05.0

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 women.NIH Web site. Your guide to lowering high blood pressure: issues for women.Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.

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 <120/80 <120/80 mm Hg through lifestyle approachesmm Hg through lifestyle approaches (Class I, (Class I, Level B)Level B)

• Pharmacotherapy when BP is Pharmacotherapy when BP is 140/90 mm Hg140/90 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. 2004;43:900-921.. 2004;43:900-921.

CHD Risk Equivalents• > 20% 10-year risk of CHD

(Framingham projections) (downloadable risk algorithms at www.nhlbi.nih.gov)

• Diabetes

• Other forms of clinical atherosclerotic disease

– Peripheral arterial disease (ABI <0.90)

– Abdominal aortic aneurysm

– Carotid artery disease (>=1mm CIMT?)

NCEP ATP III. JAMA. 2001;285:2486-2497.

Other Modalities for Measuring Atherosclerotic Burden

• Carotid B-mode ultrasonography: intimal medial thicknesses

• Ankle-Brachial Index (ABI) for assessment of peripheral vascular disease

• CT (EBT or multislice detectors): coronary calcium score or volume

• Magnetic resonance imaging of carotid plaques: vessel wall area

• Intravascular ultrasound (invasive)

Recommendations for Noninvasive Screening

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

• ATP III has suggested CAC scores above 75th percentile indications for more aggressive treatment (e.g., as CHD risk equivalent).

Cardiovascular Health Study: Combined intimal-medial thickness

predicts 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 (O’Leary et al. 1999)

Significant Coronary Artery Calcium (Score >400)

Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic IndividualsShaw LJ et al., Radiology 2003; 228: 826-33

L – Lifestyle Change: First Line of Defense Against Heart Disease

• The AHA expert panel rated the following as Class I recommendations:– Stop cigarette smoking and avoid secondhand tobacco

smoke– Get at least 30 minutes of physical activity each day– Start a cardiac rehabilitation program if recently

hospitalized for heart disease– Eat a heart-healthy diet – Maintain healthy weight by balancing caloric intake

with caloric expenditureMosca et al. Circulation 2004

ATP III: Nutritional Components of the TLC Diet

Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure tomaintain desirable body weight.

<200 mg/dCholesterol

~15% of total caloriesProtein

20–30 g/dFiber

50%–60% of total caloriesCarbohydrate (esp. complex carbs)

25%–35% of total caloriesTotal fat

Up to 20% of total caloriesMonounsaturated fat

Up to 10% of total caloriesPolyunsaturated fat

<7% of total caloriesSaturated fat*

Recommended IntakeNutrient

© 2001, Professional Postgraduate Services®

www.lipidhealth.org

Possible Benefits From Other Therapies

Therapy Result

• Soluble fiber in diet (2–8 g/d) (oat bran, fruit, and vegetables)

• Soy protein (20–30 g/d)

• Stanol esters (1.5–4 g/d) (inhibit cholesterol absorption)

• Fish oils (3–9 g/d) (n-3 fatty acids)

LDL-C 1% to 10%

LDL-C 5% to 7%

LDL-C 10% to 15%

Triglycerides 25% to 35%

Jones PJ. Curr Atheroscler Rep. 1999;1:230-235.Lichtenstein AH. Curr Atheroscler Rep. 1999;1:210-214.Rambjor GS et al. Lipids. 1996;31:S45-S49.Ripsin CM et al. JAMA. 1992;267:3317-3325.

Nuts, Soy, Phytosterols, Garlic• Nurses’ Health Study: five 1oz servings of nuts per week

associated with 40% lower risk of CHD events; 2-4 servings/wk 25% lower risk

• Metaanalysis of 38 trials of soy protein showed 47g intake lowered total, LDL-C, and trigs 9%, 13%, and 11%, respectively; no effect on HDL-C.

• Phytosterol-supplemented foods (e.g., stanol ester margarine) lowers LDL-C avg. 10%

• Meta-analysis of garlic studies showed 9% total cholesterol reduction from 1/2-1 clove consumed daily for 6 months.

Health Benefits of Weight Loss

• Decreased cardiovascular risk

• Decreased glucose and insulin levels

• Decreased blood pressure

• Decreased LDL and triglycerides, increased HDL

• Decrease in severity of sleep apnea

• Reduced symptoms of degenerative joint disease

• Improved gynecological conditions

National Obesity Education Initiative Treatment

Algorithm

Patient Encounter

Hx of 25 BMI?

•Measure weight, height, and waist circumference •Calculate BMI

Examination

Brief reinforcement/ educate on weight management

Periodic weight check

Advise to maintain weight/address 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 made/goal

achieved?

BMI 25 OR waist circumference

> 88 cm (F) > 102 cm (M)

BMI 30 OR

{[BMI 25 to 29.9 OR waist circumference

>88 cm (F) >102 cm (M)] AND 2 risk

factors}

BMImeasured in past

2 years?

Whenever possible, weight loss therapy should employ the combination of

• Low-calorie/low-fat diets

• Increased physical activity

• Behavior modification

Weight Loss Therapy

O – Other Interventions with Class I Recommendations

• Blood pressure – encourage optimal levels of <120/80 mmHg

• Cholesterol levels – optimal cholesterol levels <200 mg/dl, LDL-C< 100 mg/dl, HDL >50 mg/dl, triglycerides <150 mg/dl

• Diabetes – recommend control to HgbA1c < 7%

Evidence-based Guidelines for CVD Prevention in Women – Major Risk Factor Interventions

(Mosca et al., Arterioscler Throm Vasc Biol 2004; 24: e29-e50)

I have some bad news for you. While your cholesterol has remained the same, the research

findings have changed.

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 30–40% sufficient to achieve a 30–40%

reduction in LDL-C levels.reduction in LDL-C levels.

JNC-7 New Features and Key Messages

Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.

Certain high-risk conditions are compelling indications for other drug classes.

Most patients will require two or more antihypertensive drugs to achieve goal BP.

If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

H – Highest Priority for Therapy is for Women at Highest Risk

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

unless contraindicated– Beta-blocker therapy in those with prior MI or current angina– Statin therapy – Niacin or fibrate therapy if low HDL present– Fibrates to lower triglycerides and improve HDL– Warfarin in those with atrial fibrillation unless

contradindicated

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

• Those at highest risk, who already have pre-existing Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the likely to benefit from preventive therapy involving the following Class I recommendations: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 mg) Aspirin therapy (baby aspirin or maximum dose of 162 mg)

unless contraindicatedunless contraindicated– Beta-blocker therapy in those with prior MI or current anginaBeta-blocker therapy in those with prior MI or current angina– 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 – Avoid “Class III” Interventions – Avoid “Class III” Interventions(Not proven useful or effective / may be harmful)(Not proven useful or effective / may be harmful)

• Combined estrogen and progestin therapy, and *estrogen Combined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVDmonotherapy since associated with increased risk of CVD

• Selective estrogen-receptor modulators (SERMs) also not Selective estrogen-receptor modulators (SERMs) also not recommendedrecommended

• Antioxidant supplements including vigtamin E, C, and beta-Antioxidant supplements including vigtamin E, C, and beta-carotene 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 <65 yearsAspirin for MI prevention in women aged <65 years

Vitamins: Major Vascular Events

Vascular Event

Major coronary 1063 1047

Any stroke 511 518

Revascularization 1058 1086

Any of the above 2306 (22.5%)

2312 (22.5%)

Heart Protection Study Collaborative Group. Lancet. 2002;360:23–33.

Risk Ratio and 95% CIRisk Ratio and 95% CI

Vitamin BetterVitamin Better Vitamin WorseVitamin Worse

0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4

1.00 (0.94–1.06)P > 0.9

Vitamins (n = 10,269)

Placebo (n = 10,267)

Does Hormone Replacement Therapy Prevent Heart Disease?

• Epidemiologic studies over the past several decades together have shown approximately a 50% lower risk in women randomized to estrogen replacement therapy vs. placebo

• Even the Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events

Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD in

Women

• Randomized, placebo-controlled trial of E/P therapy vs. placebo in 2763 women with CHD; average age 67 years

• Treatment was 0.625 mg CEE + 2.5 mg medroxyprogesterone daily for 4 years

• Primary endpoint: nonfatal MI and CHD death• Secondary endpoints: CABG, PTCA, unstable

angina, CHF, PVD, TIAJAMA 1998;280:605-613

JAMA 1998;280:605-613

HERS Results• No statistically significant difference between HRT

and placebo in both primary and secondary endpoints after 4 years.

• Within first year, greater incidence in CHD events in HRT group. In years 3 and 4, lower CHD events in HRT group compared to placebo.

• HRT lowered LDL 11% and increased HDL 10% compared to placebo.

• Approximately 50% of randomized women were on lipid-lowering drugs.

• Higher incidence of VTE and cholelithiasis in HRT group.

More Bad News: The Women’s Health Initiative

• Over 160,000 women nationwide, aged 50-79 and postmenopausal have participated in various components (observational, dietary modification, and HRT clinical trials)—over 3,000 at UCI

• The Estrogen/Progestin component of the HRT clinical trial involving 16,608 women nationwide was discontinued prematurely in Spring 2002 after 5.2 years of follow-up (instead of 8.5 years).

WHI Estrogen/Progestin and Estrogen Only Results

• Those randomized to estrogen/progestin compared to placebo and statistically significant increased risks:– Breast cancer 26% (8/10,000 person years)– Total coronary heart disease 29% (7/10,000 person years)– Stroke 41% (8/10,000 person years)– Pulmonary emobolism 2.1 X (8/10,000 person years)– Protective for colorectal cancer (37% lower) and hip fracture

(34% lower): no effect endometrial cancer or total mortalityJAMA. 2002 Jul 17;288(3):321-33.

• Estrogen-only arm was also recently discontinued in December 2003 and was associated with a 39% increased risk of stroke (12 excess strokes per 10,000 person years) and 12% significant increased risk of cardiovascular events. JAMA. 2004 Apr 14;291(14):1701-12.

Women Making a ChangeWomen Making a Change

For More Information about Preventing Heart Disease:

Preventive Cardiology, 2nd ed.from McGraw-Hill …..

For more information, see the UCI Heart Disease Prevention Website at www.heart.uci.edu