CAD is multifactorial with a long latent period. Despite a 24% decline in its mortality since 1980, CAD remains a leading cause of death in Western society and has a high morbidity. Since its pathophysiologic mechanisms remain undefined, epidermiologic data have verified a number of CAD risk factors which are statistically associated with its development, although there may not necessarily be a causal relationship. Therefore, it is desirable to normalize all potential modifiable risk factors in order to prevent or delay disease progression in a high-risk asymptomatic subgroup (primary prevention) or to postpone or regress well-established lesions in patients with preexisting CAD (secondary prevention).
When should hypercholesterolemia be treated?
The positive association between elevated serum total cholesterol levels and CAD is primarily due to the high level of low density lipoprotein cholesterol (LDL-C). The current guideline provided through the National Cholesterol and Hypertension Education Program in 1993 defined a total cholesterol 240 mg/dl and LDL-C 160-170 mg/dl as a high-risk level requiring medication. Total cholesterol between 200 and 239 mg/dl and LDL-C between 130 and 159 mg/dl are considered as borderline-high, and diet control should be tried with a close follow-up. A total cholesterol 200 and LDL-C 100 mg/dl are desirable. In patients with CAD, LDL-C 100 is desirable.
What is the clinical impact of a high density lipoprotein cholesterol (HDL-C)?
HDL-C has been shown epidemiologically to have an inverse relationship to CAD. People with borderline-high total cholesterol but low HDL-C were also considered at risk for CAD, whereas those with high HDL-C (especially if the ratio of total cholesterol/HDL-C was 4.5) achieved a protective effect against atherosclerosis. Although its exact role is unclear, HDL-C is believed to work by removing cholesterol from the peripheral tissues and arterial wall, transporting it back to the liver for further degradation. Increasing the level of HDL-C can be aided by halting smoking, reducing body weight (in obese persons), controlling hypertriglyceridemia, reducing carbohydrate intake, continuing aerobic exercise, and taking estrogen supplement and nicotinic acid.
Will reduction in serum cholesterol help in primary prevention of CAD?
Evidence from three major randomized, double-blinded, placebo-controlled trials confirm the beneficial effects of cholesterol-lowering agents:
World Health Organization Trial (1978): Clofibrate, 1.6 gm/day, reduced the incidence of ischemic events 20% in the treated group compared to the control group after 5 years.
Lipid Research Clinics Coronary Primary Prevention Trial (1984): With cholestyramine, 14-24 gm/day, patients showed a 19% reduction of coronary death/nonfatal myocardial infarction rates over a 7-year period. Roughly, reducing the cholesterol level by 1% resulted in a reduction of CAD risk of about 2%.
Helinski Heart Study (1988): Gemfibrozil, 600 mg twice a day for 5 years, resulted in a 34% reduction of coronary events.