History of the cholesterol controversy in Britain.

The lipid hypothesis, the concept that cholesterol plays a causal role in atherosclerosis and cardiovascular disease, has been the subject of a controversy which started in the 1950s, peaked in the 1970s and 80s and then subsided in the 1990s. It was finally resolved by the positive outcome of the Scandinavian Simvastatin Survival Study, the first of 14 prevention trials using statins which showed that lowering cholesterol reduced both cardiovascular events and total mortality. This commentary focuses primarily on the events and people involved in the cholesterol controversy in Britain. The foremost critics of the lipid hypothesis are now deceased but unfortunately for many of the patients with hypercholesterolaemia and coronary heart disease it took the best part of 50 years to disprove the sceptics. This brief account relates why it took so long.

Simvastatin: two decades in a circle.

Simvastatin is an agent of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor group of drugs. It is administrated orally once a day in doses of 5-80 mg. Although its main action is to reduce total and low-density lipoprotein (LDL) cholesterol, it is able to reduce triglycerides and increase high-density lipoprotein cholesterol levels, though at a lower extent. Beyond this action, studies enrolled with simvastatin have shown beneficial effect on endothelial function, smooth muscle cell function, hemostasis, vascular wall function, LDL oxidation, and inflammation. All these actions mentioned above are known as pleiotropic effects. In this review, we will present all these effects, as well as the beneficial effects on atherogenesis and the reduction in cardiovascular morbidity and mortality related to simvastatin.