ABSTRACT
The introduction of the 3-hydroxy-3-methyl-glutaryl coenzyme (HMG CoA) reductase inhibitors, or statins, a decade ago was arguably the most effective addition to our strategy for the prevention of cardiovascular disease.1 These drugs, while possessing potentially diverse pharmacological properties, primarily affect the plasma lipid and lipoprotein profile – lowering total and low-density lipoprotein (LDL) cholesterol with the additional effects of raising high-density lipoprotein (HDL) cholesterol and lowering triglyceride levels. Although we can glean much from the many epidemiological studies that have examined the relationship between lipid levels and risk of cardiovascular disease, it is perhaps more informative to look in detail at the largescale lipid-lowering trials. These studies set out to examine the impact of lipid-lowering drugs on the risk of major cardiovascular events in a wide variety of patient groups. In so doing they also set out to prove the lipid hypothesis, which states that an elevated plasma cholesterol level is causally associated with cardiovascular risk and that in lowering cholesterol we will reduce that risk. Here we will review these studies rather than looking in detail at the large portfolio of epidemiological data, for the results of the intervention trials take us beyond epidemiology and provide a clear blueprint for preventive cardiology with lipid-modifying therapy. First, however, it is useful to discuss the role of lipids in the development of atherosclerotic disease, and to examine in detail the mechanisms of action of the most widely used lipid-modifying therapy – the statins.
