Potential vascular benefits of statins

Atherosclerosis is associated with a number of functional abnormalities that affect endothelium-dependent vasomotor function, inflammation, and thrombosis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects on many of these functions, likely explaining their benefit in reducing the incidence of clinical events in patients at high risk of cardiovascular disease. Statins may improve this vascular biology by lowering levels of low-density lipoprotein (LDL) or potentially by a number of non–LDL-related mechanisms. Cell culture and some animal studies have demonstrated LDL-independent effects of statins. The non-LDL mechanisms include effects on isoprenoid production and function, interactions between caveolin and nitric oxide synthase, and direct immunomodulatory effects. Although these mechanisms are clearly demonstrated in the experimental setting, their relevance to the clinical use of statins is unknown. From a purely pragmatic viewpoint, the debate of lipid versus nonlipid effects of statins matters little to clinical practice. Their proven effect on vascular biology and risk reduction justifies their important therapeutic role.