Prevention of Coronary Prevention of Coronary Artery DiseaseArtery Disease

PAS-880PAS-880

Robert D. Hadley, PhD, PA-CRobert D. Hadley, PhD, PA-C

July 19, 2001July 19, 2001

What is CAD?What is CAD?

Coronary artery insufficiency and Coronary artery insufficiency and blockage, resulting in angina and MIblockage, resulting in angina and MI

CAD is one facet of CAD is one facet of systemicsystemic vascular vascular diseasedisease Vascular disease is largely due to inflammatory Vascular disease is largely due to inflammatory

mechanisms in the vascular endotheliummechanisms in the vascular endothelium Lesser contribution of “cholesterol buildup”Lesser contribution of “cholesterol buildup”

Vascular Endothelial Vascular Endothelial DysfunctionDysfunction

Related to multiple disease processesRelated to multiple disease processes Oxidative damage to endothelial cellsOxidative damage to endothelial cells

Much related to mechanical stress of Much related to mechanical stress of HTNHTN

Lipids Lipids Accelerated atherosclerosis when Accelerated atherosclerosis when

combined with oxidative damagecombined with oxidative damage

Cardiovascular Dysmetabolic Cardiovascular Dysmetabolic SyndromeSyndrome

““Syndrome X”:Syndrome X”: Increased triglycerides, LDL, decreased Increased triglycerides, LDL, decreased

HDLHDL Obesity (esp. central)Obesity (esp. central) HTNHTN Diabetes/ glucose intolerance/ insulin Diabetes/ glucose intolerance/ insulin

resistance/ hyperinsulinemiaresistance/ hyperinsulinemia Increased PAI-1, inflammatory markersIncreased PAI-1, inflammatory markers

PAI-1PAI-1

Plasminogen Activator InhibitorPlasminogen Activator Inhibitor Plasmin comes from plasminogen, and Plasmin comes from plasminogen, and

dissolves clotsdissolves clots Plasminogen is activated by Plasminogen Plasminogen is activated by Plasminogen

ActivatorActivator PAI-1 inhibits PA, resulting in PAI-1 inhibits PA, resulting in

hypercoaguabilityhypercoaguability PAI-1/PA should be in balancePAI-1/PA should be in balance

Coronary Artery DiseaseCoronary Artery Disease

Unstable plaque, rather Unstable plaque, rather than gradual arterial than gradual arterial narrowing is the problem narrowing is the problem in MIin MI

Controlling factors that Controlling factors that lead to plaque (especially lead to plaque (especially unstable) will reduce risk unstable) will reduce risk of CADof CAD

Risk FactorsRisk Factors

Uncontrollable Risk FactorsUncontrollable Risk Factors Controllable Risk FactorsControllable Risk Factors

Uncontrollable Risk FactorsUncontrollable Risk Factors

HeredityHeredity GenderGender AgeAge

Choose your Choose your parents wellparents well

Choose your Choose your gender wellgender well

Don’t ageDon’t age

Controllable Risk FactorsControllable Risk Factors

HypertensionHypertension DiabetesDiabetes ObesityObesity HyperlipidemiaHyperlipidemia SmokingSmoking Sedentary LifestyleSedentary Lifestyle StressStress

HypertensionHypertension

Damage to vascular endotheliumDamage to vascular endothelium AHA goalsAHA goals

140/90 if no other risk factors140/90 if no other risk factors 135/85 (or lower) if other CV risk factors135/85 (or lower) if other CV risk factors

Lifestyle changes– everyone!Lifestyle changes– everyone! MedicinesMedicines

ACE-I/ ARB, ACE-I/ ARB, -blockers, diuretics-blockers, diuretics

DiabetesDiabetes

DCCT and UKPDS trials showed DCCT and UKPDS trials showed benefits of controlling sugarbenefits of controlling sugar

Especially impt. to control HTN Especially impt. to control HTN (Syndrome X)(Syndrome X)

UKPDS trial showed benefit of UKPDS trial showed benefit of specific drugs in reducing CV riskspecific drugs in reducing CV risk

Combination therapy and exerciseCombination therapy and exercise

ObesityObesity

Epidemic, especially in US (Syndrome X)Epidemic, especially in US (Syndrome X) Lose weight to “normal range”, with BMI of Lose weight to “normal range”, with BMI of

18.5-24.9 (BMI= wt./height18.5-24.9 (BMI= wt./height22, kg/m, kg/m22)) J-shaped curve for overall mortalityJ-shaped curve for overall mortality Rate of 10% of body wt. over 6 mo, 1-2 Rate of 10% of body wt. over 6 mo, 1-2

lb/wk, avoid yo-yo effectlb/wk, avoid yo-yo effect 1 lb = 3,500 Calories intake1 lb = 3,500 Calories intake

J-Shaped CurveJ-Shaped Curve

HyperlipidemiaHyperlipidemia

Clear increased risk with elevated lipidsClear increased risk with elevated lipids Goals depend on other risk factors, likely Goals depend on other risk factors, likely

to be revised soon by NCEPto be revised soon by NCEP HDL>60, LDL<100/80, TG<200 for high HDL>60, LDL<100/80, TG<200 for high

risk personrisk person Statins (HMG Co-A reductase inhibitors) Statins (HMG Co-A reductase inhibitors)

probably have special statusprobably have special status

SmokingSmoking

Don’t do itDon’t do it Multiple substances contribute to Multiple substances contribute to

inflammatory reaction in vascular inflammatory reaction in vascular endotheliumendothelium

Cessation is extremely difficultCessation is extremely difficult Nicotine itself is not the culprit, use Nicotine itself is not the culprit, use

nicotine replacements, keep tryingnicotine replacements, keep trying Nicotine more addictive than heroinNicotine more addictive than heroin

Sedentary LifestyleSedentary Lifestyle

Exercise!Exercise! But how?But how?

Moderate aerobic exercise better than Moderate aerobic exercise better than strenousstrenous

WalkingWalking is usually best form of exercise is usually best form of exercise Accessible, no specialized equipment neededAccessible, no specialized equipment needed Easily modulated, to maintain appropriate level of Easily modulated, to maintain appropriate level of

exertionexertion 30 min, 3 times a week, fast enough to slightly increase 30 min, 3 times a week, fast enough to slightly increase

breathing ratebreathing rate

StressStress

Contribution unclear, but has an effect Contribution unclear, but has an effect on immune function and promotes on immune function and promotes inflammatory mediatorsinflammatory mediators

Exercise is best stress reducerExercise is best stress reducer Other lifestyle modifications as Other lifestyle modifications as

necessary (divorce, etc.)necessary (divorce, etc.)

Alcohol?Alcohol?

What kind of EtOH?What kind of EtOH? Recent report* shows all-cause mortality Recent report* shows all-cause mortality

benefit (much cardiovascular) of all kinds of benefit (much cardiovascular) of all kinds of EtOH, but wine a little betterEtOH, but wine a little better

1-2 drinks/day for men, 1/2-1 /day for 1-2 drinks/day for men, 1/2-1 /day for womenwomen

J-shaped curveJ-shaped curve

*Ann. Int. Med. 133(6):411-419, 2000

AspirinAspirin

Low dose aspirin of proven benefitLow dose aspirin of proven benefit 81-325 mg qd or qod81-325 mg qd or qod Enteric coatedEnteric coated

Few contraindicationsFew contraindications Decreases clotting pathway and Decreases clotting pathway and

prevents thromboembolismprevents thromboembolism

Hormone ReplacementHormone Replacement

Postmenopausal estrogen replacement Postmenopausal estrogen replacement previously thought to be strongly previously thought to be strongly cardioprotective, with 25-50% reduction in cardioprotective, with 25-50% reduction in risk of CVDrisk of CVD

HERS study* and others** have HERS study* and others** have questioned this effectquestioned this effect

Other benefits still hold, but jury is still out Other benefits still hold, but jury is still out on CVDon CVD

*JAMA 280:605-613, 1998

**NEJM 343(8):522-529, 2000

Recent Report on HRT:Recent Report on HRT:

Low dose estrogen and estrogen/ Low dose estrogen and estrogen/ progesterone (0.45 mg vs. usual 0.625 mg), progesterone (0.45 mg vs. usual 0.625 mg), some dose-related differencessome dose-related differences

10% increase in HDL, 5% decrease in LDL 10% increase in HDL, 5% decrease in LDL after 1 yr of 0.45 mg estrogenafter 1 yr of 0.45 mg estrogen

Improved thrombogenic markers (PAI-1, Improved thrombogenic markers (PAI-1, plasminogen)plasminogen)

Relatively young population (avg 51 yo)Relatively young population (avg 51 yo)

Fertility and Sterility 76(1): 13-24, July, 2001Fertility and Sterility 76(1): 13-24, July, 2001

Patient EducationPatient Education

Assess risk factors and inform Pt.Assess risk factors and inform Pt. Smoking cessation, exercise, adherence to other Smoking cessation, exercise, adherence to other

disease management plansdisease management plans

If Pt. drinks, inform about the benefits of If Pt. drinks, inform about the benefits of moderationmoderation

Inquire about and assess readiness to change, Inquire about and assess readiness to change, reassess at follow-upreassess at follow-up If you give up, the patient surely willIf you give up, the patient surely will If you don’t give up, the patient may change– If you don’t give up, the patient may change–

eventuallyeventually