Vascular pleiotropy of statins: clinical evidence and biochemical mechanisms.

The ability of statins to lower serum cholesterol and reduce coronary heart disease endpoints has confirmed portions of the lipid hypothesis. However, the time to benefit and increased benefit in overlapping populations have suggested that nonlipid or pleiotropic effects of statins may be present. The apparent benefit of statins in cerebrovascular disease may imply a similar final common pathway among the diverse mechanisms of vascular diseases. Statins' inhibition of isoprenoid intermediates may modify GTP binding proteins such as Rho. The augmentation of collateral blood flow downstream of activated plaque through endothelial cell nitric oxide synthase may be the biochemical basis of statins' vascular pleiotropy. Eventual clinical paradigms of statin use may include higher doses to enhance pleiotropic effects and treatment, even when lipid markers are within guidelines.