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Non-lipid effects of statins

 

Clinical bottom line

Statins appear to have a number of potentially beneficial effects, some of which are independent of their cholesterol-lowering effect, and this could increase the number of circulatory disorders in which they could help.


Background

Statins are undeniably good at altering lipid profiles and reducing morbidity and mortality associated with unfavourable lipid levels. It takes four to six weeks of treatment for plasma lipid levels to show changes, and longer for tissue lipid levels. Some of the benefits seen during therapy occur too early to be the direct consequence of lipid changes. It was recognised in the late 1980s and early 1990s that statins improve endothelial function, but this was attributed directly to their lipid-lowering effects, and it was not until 1997 that they were shown to have direct effects on the endothelium. Endothelial dysfunction is an early critical component of organ injury after acute events such as myocardial infarction, ischaemic stroke and haemorrhage, and in chronic disease states such as diabetes and hypercholesterolaemia. It is a good prognostic indicator for cardiac events and mortality, so an important target for intervention.

Many studies, using animal and human cell lines and animal models, suggest a number of important effects of statins, mostly related to the bioavailability of nitric oxide (NO) in the vascular endothelium. For those who want to get involved in the detailed biochemistry, there are useful reviews [1, 2, 3, 4], but for the rest of us, the main effects are include:

Do these laboratory findings translate into clinical benefit?

Some of these clinical benefits have been studied in small groups of patients, or in sub-groups of larger clinical trials. Further large, prospective, randomised trials are needed to confirm them and establish their clinical importance. It does seem, however, that statins have a number of potentially beneficial effects, some of which are independent of their cholesterol-lowering effect, and this could increase the number of circulatory disorders in which they could help.

References


  1. J Davignon. The cardioprotective effects of statins. Curr Atheroscler Rep 2004 6: 27-35.
  2. AM Lefer et al. Vascular effects of HGM CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease. Cardiovasc Res 2001 49: 281-287.
  3. S Tsiara et al. Early vascular benefits of statin therapy. Curr Med Res Opin 2003 19: 540-556.
  4. S Wolfrum et al. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol 2003 23: 729-736.