Review of clinical trials: proving the lipid hypothesis

The Lipid Hypothesis, which states that lowering blood cholesterol levels should significantly reduce the incidence of coronary heart disease (CHD), has been repeatedly tested in primary and secondary intervention trials. Viewed as a whole, it is apparent that the incidence of CHD in treated groups decreased in proportion to the degree of plasma cholesterol redaction. An early study at the Wadsworth Hospital in Los Angeles showed that a diet high in polyunsaturatedfat and low in cholesterol reduced the incidence of CHD. The Oslo study of diet and smoking intervention demonstrated a signficant decrease in CHD concomitant with a 13% reduction in serum cholesterol achieved through a low saturated-fat diet and cessation of smoking. In the World Health Organization primary prevention trial, clofibrate reduced serum cholesterol by 9% and first clinical episodes of myocardial infarction by 20%. There was a 37% rise in total mortality, but no causal link with clofibrate has been found, and this was not significant when corrected for age at death. A secondary trial, the Coronary Drug Project, demonstrated that oestrogen and dextrothyroxine were clearly toxic. In this trial, niacin produced a 10%fallin serum cholesterol and mortality was 11% lower than in the placebo group after long-term follow-up. The Lipid Research Clinics-Coronary Primary Prevention Trial (LRC-CPPT) found an 8% reduction in plasma cholesterol and a 19% reduction in the incidence of CHD in the group treated with.cholestyramine compared with placebo. More recently, the Helsinki Heart Study found a 10% increase in high density lipoprotein (HDL)-cholesterol and a 10% redaction in low density lipoprotein (LDL)-cholesterol in the gemfibrozil-treated group compared with placebo. The active treatment group also experienced a 34% reduction in the incidence of CHD compared with placebo. The Helsinki investigators concluded that the alterations in both the LDL-cholesterol and HDL-cholesterol contributed to the reduction in CHD. In the secondary prevention Cholesterol Lowering Atherosclerosis Study of men with angiographically demonstrated arterial lesions and bypass grafts, the group treated with colestipol plus nicotinic acid experienced a 43% reduction in LDL-cholesterol and a 37% increase in HDL-cholesterol as well as reduced rates of progression of lesions in native vessels and venous grafts. These and other studies indicate that increases in HDL-cholesrerol lead to decreases in CHD.