The lipid and non-lipid effects of statins

The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, more commonly known as statins, are a class of drug widely used for the treatment of hypercholesterolaemia in patients with established cardiovascular disease as well as those at high risk of developing atherosclerosis. Their predominant action is to reduce circulating levels of low-density lipoprotein (LDL) cholesterol; to a smaller degree, they also increase high-density lipoprotein (HDL) cholesterol and reduce triglyceride concentrations. In recent years, however, there has been an increasing body of evidence that their effects on lipid profile cannot fully account for their cardiovascular protective actions: their beneficial effects are too rapid to be easily explained by their relatively slow effects on atherogenesis and too large to be accounted for by their relatively small effects on plaque regression. Experimental models have revealed that statins exert a variety of other cardiovascular effects, which would be predicted to be of clinical benefit: they possess anti-inflammatory properties, as evidenced by their ability to reduce the accumulation of inflammatory cells in atherosclerotic plaques; they inhibit vascular smooth muscle cell proliferation, a key event in atherogenesis; they inhibit platelet function, thereby limiting both atherosclerosis and superadded thrombosis; and they improve vascular endothelial function, largely through augmentation of nitric oxide (NO) generation. The relative importance of the lipid- and non-lipid-related effects of the statins in the clinical situation remains the subject of much continuing research.