Virchow (1821 – 1902), the German pathologist and one of the 19th century's foremost leaders in medicine and pathology, observed that the artery walls of patients dying of occlusive vascular disease, such as myocardial infarction, were often thickened and irregular, and contained a yellowish fatty substance. This pathological condition was termed atheroma, the Greek word for porridge, and subsequently identified as cholesterol. Anitschkow and Chalatow in 1913 showed that feeding cholesterol to rabbits rapidly produces atheromatous disease similar to that found in man.
However, at that time, physicians were not convinced of any causal link between cholesterol and coronary heart disease (CHD) because most patients with the disease have plasma cholesterol levels not much different from that of the general population average.
The Framingham study, led by Dawber, was initiated in the 1950s to prospectively study the relationship between blood cholesterol and other potential risk factors and death from coronary disease. This work established an increasingly strong correlation between high plasma cholesterol and CHD mortality, which was confirmed by many other population-based studies. Moreover, the Seven Countries Study, which was initiated in the 1950s, showed that northern European countries and the United States had both high plasma cholesterol and high CHD mortality rates. By contrast, plasma cholesterol and CHD mortality were both substantially lower in southern Europe, and even more so in Japan. Later investigations established that the association with CHD mortality was attributable mainly to low-density lipoprotein (LDL) cholesterol. Subsequent studies showed that LDL cholesterol comprises about 70% of total cholesterol and that high-density lipoprotein (HDL) cholesterol is inversely correlated with CHD mortality.
The above findings lead to the Lipid Hypothesis, which proposed that elevated total, or more accurately LDL, cholesterol was causally related to coronary disease and that reducing it would reduce the risk of myocardial infarction and other coronary events. This hypothesis remained controversial for many years because of the lack of clear evidence that lowering cholesterol provided any clinical benefits.
Before the discovery of statins (HMG-CoA reductase inhibitors), a number of dietary intervention studies and a few drug studies had reported a reduction in CHD events in patients with and without CHD. No individual study was compelling enough but taken together, there seemed to be a trend that lowering cholesterol reduced the risk of coronary events. On the basis of those studies and the National Institutes of Health (NIH) Coronary Primary Prevention Trial (USA), an NIH Consensus Conference convened in 1984 concluded that lowering elevated LDL cholesterol with diet and drugs would reduce the risk of CHD. The NIH (USA) accepted the findings of the Consensus Conference and the following year initiated a massive program to educate physicians and the public about the importance of treating hypercholesterolemia.