Acute effects of statins.

In addition to lowering low-density lipoprotein cholesterol, statins improve vascular function by cholesterol-independent effects in experimental models. These extrahepatic effects are often called “pleiotropic”; however, specific underlying molecular mechanisms have been identified in animal and cell culture studies. They relate to the inhibition of isoprenylation of small G proteins. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase blocks the synthesis of isoprenoids, which are upstream of cholesterol (1,2). Therefore, statins inhibit isoprenoid and cholesterol synthesis at the same time, making it difficult to assess the relative contribution of the 2 for the reduction of vascular events. One could speculate that their importance may depend on the clinical situation. There is no doubt regarding the long-term importance of low-density lipoprotein cholesterol for atherogenesis. The isoprenoid-dependent effects (Fig. 1), however, may be especially important for the acute effects of statin treatment.