Does lowering serum cholesterol levels lower coronary heart disease risk?

Many lines of evidence converge toward the conclusion that low-density lipoprotein cholesterol (LDLC) is indeed a causal factor in the genesis of CHD. These range from animal studies, pathology studies, inborn errors of metabolism, clinical observations, and the existence of plausible biologic mechanisms, to the vast body of epidemiologic evidence. Observations of the association of LDLC with CHD hold between different populations, in the same population at different times, and to studies of individuals within populations. Finally, the clinical trials of cholesterol lowering, together with regression studies in animals and angiographic studies in humans, provide compelling evidence that the progress of atherosclerosis can be halted and the clinical sequelae can be reduced. The newly available results from more recent intervention studies have reinforced the validity of this conclusion. The intervention studies reduced the CHD incidence rate by approximately 2% for every 1% reduction in total cholesterol (TC) even though the studies were of relatively short duration (typically 5 years). More prolonged exposure to lower TC levels can be expected to yield even greater ultimate benefit. The benefit is most clearcut for men at highest risk. The combined data indicate that both fatal and nonfatal CHD can be reduced. More data on the extremes of age, on subjects with moderate elevations of TC, and on women would be valuable, but it is reasonable to proceed with advice to the general population aimed at reducing average cholesterol levels, and also to identify and treat those at high risk. There is good reason to expect that these measures will further reduce MI events and in all likelihood also MI deaths. Whether they will also reduce overall mortality is at present a moot point; however, a reduction in the burden of nonfatal MI would in itself be a very desirable objective.