New nonlipid effects of statins and their clinical relevance in cardiovascular disease

Thromb Haemost. 2004 Jun;91(6):1065-77. doi: 10.1160/TH04-02-0064.


Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, statins, have been demonstrated to reduce cardiovascular morbidity and mortality in patients with a wide range of cholesterol levels. Numerous cholesterol-independent effects of statins that may limit atherosclerosis are probably related to inhibition of the geranylgeranylation of GTP-binding intracellular signaling proteins and involve: improved vasoreactivity, mostly through increased NO bioavailability; decreased expression of proinflammatory cytokines (interleukin-6, interleukin-1 beta, tumor necrosis factor alpha), C-reactive protein, chemokines, matrix metalloproteinases, and tissue factor with the subsequent inhibition of thrombin generation; reduced platelet activity; increased thrombomodulin expression; enhanced fibrinolysis, regulation of angiogenesis and immunomodulation. However, the clinical relevance of multiple protective effects induced by statins has not been clarified yet.

Publication types

  • Review

MeSH terms

  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / pathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology


  • Cardiotonic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors