Total serum cholesterol and ischemic heart disease risk in clinical trials and observational studies.

Despite compelling evidence that elevated plasma total and low-density lipoprotein cholesterol plays a causal role in ischemic heart disease (IHD) (evidence derived from molecular biologic, genetic, animal experimental, and human observational studies), the results of individual clinical trials testing the lipid hypothesis have not been regarded as conclusive. Analyzed in aggregate, however, the trials results indicate a dose-response relationship between amount of cholesterol lowering and reduction of ischemic heart disease risk. This summary analysis predicted the quantitative measure of efficacy in the recently completed Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). There was a quantitatively similar relationship between the amount of IHD risk reduction associated with amount of total plasma cholesterol reduction within the active drug (cholestyramine) treated group. Further, the risk function relating baseline level of total plasma cholesterol to ischemic heart disease incidence in community-based studies such as Framingham was so similar to the risk function of the LRC-CPPT placebo group that it accurately predicted the ischemic heart disease events in the trial. These findings in aggregate provide strong confirmation of the lipid hypothesis, indicate that lowering total plasma cholesterol in middle-aged hypercholesterolemic men will reduce ischemic heart disease risk, and suggest that some extrapolation of the results to lower levels of plasma cholesterol is appropriate. However, aggregate evidence that supports the lipid hypothesis should be distinguished from that required for intervention and treatment programs. Instituting the latter requires the review and evaluation of the evidence relating cholesterol levels and cholesterol reduction not only to ischemic heart disease, but also to other outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)