Department of Cardiovascular Medicine, University of Oxford, West Wing Level 6, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford UK.
Curr Pharm Des. 2012;18(11):1519-30. doi: 10.2174/138161212799504803.
Ample evidence exists in support of the potent anti-inflammatory properties of statins. In cell studies and animal models statins exert beneficial cardiovascular effects. By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation, favorably modulate vascular and myocardial redox state and improve nitric oxide bioavailability. Randomized clinical trials have demonstrated that further to their lipid lowering effects, statins are useful in the primary and secondary prevention of coronary heart disease (CHD) due to their anti-inflammatory potential. The landmark JUPITER trial suggested that in subjects without CHD, suppression of low-grade inflammation by statins improves clinical outcome. However, recent trials have failed to document any clinical benefit with statins in high risk groups, such in heart failure or chronic kidney disease patients. In this review, we aim to summarize the existing evidence on statins as an anti-inflammatory agent in atherogenesis. We describe the molecular mechanisms responsible for the antiinflammatory effects of statins, as well as clinical data on the non lipid-lowering, anti-inflammatory effects of statins on cardiovascular outcomes. Lastly, the controversy of the recent large randomized clinical trials and the issue of statin withdrawal are also discussed.
大量证据支持他汀类药物具有强大的抗炎特性。在细胞研究和动物模型中，他汀类药物发挥了有益的心血管作用。通过抑制细胞内异戊二烯的形成，他汀类药物抑制血管和心肌炎症，有利地调节血管和心肌氧化还原状态，并提高一氧化氮的生物利用度。随机临床试验表明，除了降低血脂的作用外，由于其抗炎潜力，他汀类药物在冠心病（CHD）的一级和二级预防中也很有用。里程碑式的 JUPITER 试验表明，在没有 CHD 的受试者中，他汀类药物抑制低度炎症可改善临床结局。然而，最近的试验未能证明他汀类药物在心力衰竭或慢性肾脏病患者等高危人群中有任何临床获益。在这篇综述中，我们旨在总结他汀类药物作为动脉粥样硬化中抗炎剂的现有证据。我们描述了他汀类药物抗炎作用的分子机制，以及他汀类药物在降低血脂之外对心血管结局的抗炎作用的临床数据。最后，还讨论了最近大型随机临床试验的争议以及他汀类药物停药的问题。
