Low-density lipoprotein-independent effects of statins.

Statins have pleiotropic properties that complement their cholesterol-lowering effects. These properties may partly account for their established benefit in the prevention of coronary artery disease beyond the reduction of LDL-cholesterol levels. The most widely recognized properties are reviewed here. They include: (i) nitric oxide-mediated improvement of endothelial dysfunction and upregulation of endothelin-1 expression; (ii) antioxidant effects; (iii) anti-inflammatory properties; (iv) inhibition of cell proliferation with anticarcinogenic actions in animals; (v) stabilization of atherosclerotic plaques; (vi) anticoagulant effects; and (vii) inhibition of graft rejection after heart and kidney transplantation. As advances are made in our knowledge, new properties are steadily being uncovered. Pleiotropic effects are currently being given consideration when instituting combination therapy for patients at high cardiovascular risk. Some pleiotropic effects are negative, and may account for occasional untoward drug interactions. For many of these new properties, the clinical relevance has not been established. The challenge for the future will be to design and carry out appropriate clinical trials to establish their relative importance in the prevention of coronary artery disease.