1. Prevention of Coronary Artery Disease PAS-880 Robert D. Hadley, PhD, PA-C July 19, 2001

2. What is CAD? v Coronary artery insufficiency and blockage, resulting in angina and MI v CAD is one facet of systemic vascular disease v Vascular disease is largely due to inflammatory mechanisms in the vascular endothelium v Lesser contribution of “cholesterol buildup”

3. Vascular Endothelial Dysfunction v Related to multiple disease processes v Oxidative damage to endothelial cells v Much related to mechanical stress of HTN v Lipids v Accelerated atherosclerosis when combined with oxidative damage

4. Cardiovascular Dysmetabolic Syndrome “Syndrome X”: v Increased triglycerides, LDL, decreased HDL v Obesity (esp. central) v HTN v Diabetes/ glucose intolerance/ insulin resistance/ hyperinsulinemia v Increased PAI-1, inflammatory markers

5. PAI-1 v Plasminogen Activator Inhibitor v Plasmin comes from plasminogen, and dissolves clots v Plasminogen is activated by Plasminogen Activator v PAI-1 inhibits PA, resulting in hypercoaguability v PAI-1/PA should be in balance

6. Coronary Artery Disease v Unstable plaque, rather than gradual arterial narrowing is the problem in MI v Controlling factors that lead to plaque (especially unstable) will reduce risk of CAD

7. Risk Factors v Uncontrollable Risk Factors v Controllable Risk Factors

8. Uncontrollable Risk Factors v Heredity v Gender v Age 4 Choose your parents well 4 Choose your gender well 4 Don’t age

9. Controllable Risk Factors v Hypertension v Diabetes v Obesity v Hyperlipidemia v Smoking v Sedentary Lifestyle v Stress

10. Hypertension v Damage to vascular endothelium v AHA goals v 140/90 if no other risk factors v 135/85 (or lower) if other CV risk factors v Lifestyle changes– everyone! v Medicines  ACE-I/ ARB,  -blockers, diuretics

11. Diabetes v DCCT and UKPDS trials showed benefits of controlling sugar v Especially impt. to control HTN (Syndrome X) v UKPDS trial showed benefit of specific drugs in reducing CV risk v Combination therapy and exercise

12. Obesity v Epidemic, especially in US (Syndrome X) v Lose weight to “normal range”, with BMI of 18.5-24.9 (BMI= wt./height 2, kg/m 2 ) v J-shaped curve for overall mortality v Rate of 10% of body wt. over 6 mo, 1-2 lb/wk, avoid yo-yo effect v 1 lb = 3,500 Calories intake

13. J-Shaped Curve

14. Hyperlipidemia v Clear increased risk with elevated lipids v Goals depend on other risk factors, likely to be revised soon by NCEP v HDL>60, LDL 60, LDL<100/80, TG<200 for high risk person v Statins (HMG Co-A reductase inhibitors) probably have special status

15. Smoking v Don’t do it v Multiple substances contribute to inflammatory reaction in vascular endothelium v Cessation is extremely difficult v Nicotine itself is not the culprit, use nicotine replacements, keep trying v Nicotine more addictive than heroin

16. Sedentary Lifestyle v Exercise! v But how? v Moderate aerobic exercise better than strenous v Walking is usually best form of exercise v Accessible, no specialized equipment needed v Easily modulated, to maintain appropriate level of exertion v 30 min, 3 times a week, fast enough to slightly increase breathing rate

17. Stress v Contribution unclear, but has an effect on immune function and promotes inflammatory mediators v Exercise is best stress reducer v Other lifestyle modifications as necessary (divorce, etc.)

18. Alcohol? v What kind of EtOH? v Recent report* shows all-cause mortality benefit (much cardiovascular) of all kinds of EtOH, but wine a little better v 1-2 drinks/day for men, 1/2-1 /day for women v J-shaped curve *Ann. Int. Med. 133(6):411-419, 2000

19. Aspirin v Low dose aspirin of proven benefit v 81-325 mg qd or qod v Enteric coated v Few contraindications v Decreases clotting pathway and prevents thromboembolism

20. Hormone Replacement v Postmenopausal estrogen replacement previously thought to be strongly cardioprotective, with 25-50% reduction in risk of CVD v HERS study* and others** have questioned this effect v Other benefits still hold, but jury is still out on CVD *JAMA 280:605-613, 1998 **NEJM 343(8):522-529, 2000

21. Recent Report on HRT: v Low dose estrogen and estrogen/ progesterone (0.45 mg vs. usual 0.625 mg), some dose-related differences v 10% increase in HDL, 5% decrease in LDL after 1 yr of 0.45 mg estrogen v Improved thrombogenic markers (PAI-1, plasminogen) v Relatively young population (avg 51 yo) Fertility and Sterility 76(1): 13-24, July, 2001

22. Patient Education v Assess risk factors and inform Pt. v Smoking cessation, exercise, adherence to other disease management plans v If Pt. drinks, inform about the benefits of moderation v Inquire about and assess readiness to change, reassess at follow-up v If you give up, the patient surely will v If you don’t give up, the patient may change– eventually