Dose-dependency in pleiotropic effects of atorvastatin

Abstract

Statins are recognized as the principal and most effective class of drugs for reducing serum cholesterol levels and, therefore, significantly reducing cardiovascular events and mortality. Statins may have a wide range of beneficial biological effects in addition to lipid lowering, a phenomenon commonly termed a ‘pleiotropic effect’. However, the dose-dependency of these effects remains unclear. The present study evaluated whether atorvastatin, a potent statin, ameliorates the serum markers of pleiotropic effects, with a focus on dose-dependency. The pleiotropic effects of treatment with atorvastatin 5 mg/day and 10 mg/day for six months each in 15 patients with primary hypercholesterolemia were assessed in a prospective, randomized, open- label, crossover, single-centre study. Atorvastatin treatment dose-dependently decreased a serum marker of oxidative stress as well as the serum low-density lipoprotein cholesterol level. However, serum markers of inflammation and fibrinolysis decreased independently of dose. In conclusion, the dose-dependency of atorvastatin’s pleiotropic effects differs among individual biological effects.