Clinical implications for statin pleiotropy

Curr Opin Lipidol. 2005 Dec;16(6):624-9. doi: 10.1097/01.mol.0000191913.16321.60.


Purpose of review: Atherosclerosis is a multi-factorial condition involving dyslipidemia that can result in cardiovascular disease. Statins are potent inhibitors of cholesterol biosynthesis, and in clinical trials, statins have been shown to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to occur much earlier and to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering.

Summary of findings: Recent studies indicate that some of the cholesterol-independent or 'pleiotropic' effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent upon isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

Summary: The potential clinical implications of statin pleiotropy suggests that perhaps other biomarkers, in addition to lipid levels, should be used to gauge the full efficacy of statin therapy in patients with cardiovascular risks or that statin therapy may be effective in disease states, such as inflammatory conditions, ischemic stroke or cancer, where elevated cholesterol levels have not been shown to be a strong epidemiological risk for these diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atherosclerosis / blood
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • Cholesterol / blood*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Risk Factors


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol