Low-density lipoprotein-independent effects of statins

Statins have pleiotropic properties that complement their cholesterol-lower ing effects. These properties may partly account for their established bene fit in the prevention of coronary artery disease beyond the reduction of LD L-cholesterol levels. The most widely recognized properties are reviewed he re. They include: (i) nitric oxide-mediated improvement of endothelial dysf unction and upregulation of endothelin-1 expression; (ii) antioxidant effec ts; (iii) anti-inflammatory properties; (iv) inhibition of cell proliferati on with anticarcinogenic actions in animals; (v) stabilization of atheroscl erotic plaques; (vi) anticoagulant effects; and (vii) inhibition of graft r ejection after heart and kidney transplantation. As advances are made in ou r knowledge, new properties are steadily being uncovered. Pleiotropic effec ts are currently being given consideration when instituting combination the rapy for patients at high cardiovascular risk. Some pleiotropic effects are negative, and may account for occasional untoward drug interactions. For m any of these new properties, the clinical relevance has not been establishe d. The challenge for the future will be to design and carry out appropriate clinical trials to establish their relative importance in the prevention o f coronary artery disease. Curr Opin Lipidol 10:543-559, (C) 1999 Lippincot t Williams & Wilkins.