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他汀类药物的多效性作用:除降低 LDL 胆固醇之外的获益证据。

Pleiotropic effects of statins: evidence for benefits beyond LDL-cholesterol lowering.

机构信息

Cardiothoracic Department, University of Pisa, Pisa, Italy.

出版信息

Am J Cardiovasc Drugs. 2010;10 Suppl 1:3-9. doi: 10.2165/1153644-S0-000000000-00000.

Abstract

Evidence is mounting that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have a number of pleiotropic effects over and above their lipid-lowering properties in patients with cardiovascular disease and heart failure. In addition to lowering low-density lipoprotein cholesterol and triglyceride levels, several studies have shown statins to improve survival and reduce the risk of major cardiovascular events in patients without established cardiovascular disease but with cardiovascular risk factors. Statins have also been shown to have beneficial effects, including a reduction in all-cause mortality, in patients with ischemic and non-ischemic congestive heart failure, and have been associated with a reduced incidence of atrial fibrillation. Furthermore, statins have been associated with improvements in renal function in patients with pre-existing renal disease or the prevention of new-onset renal dysfunction, as well as improvements in lung function in patients with chronic obstructive pulmonary disease or age-related decline in lung function. The pleiotropic effects of statins appear to result from improvements in endothelial function, a reduction in inflammatory mediators, a decline in the development of atheroma through the stabilization of atheromatous plaques, and the inhibition of cardiac hypertrophy through an antioxidant mechanism. Long-term statin use may reduce morbidity and mortality rates in a broad range of patients, and most patients at high risk of cardiovascular disease may benefit from statin treatment; however, further data are required to demonstrate conclusively whether these trends are truly independent of the lipid-lowering effects of statins.

摘要

越来越多的证据表明,3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂(他汀类药物)除了具有降低心血管疾病和心力衰竭患者的血脂作用外,还具有多种多效作用。除了降低低密度脂蛋白胆固醇和甘油三酯水平外,几项研究还表明他汀类药物可改善无明确心血管疾病但存在心血管危险因素患者的生存率并降低主要心血管事件的风险。他汀类药物还具有有益作用,包括降低全因死亡率,在缺血性和非缺血性充血性心力衰竭患者中,并与房颤发生率降低相关。此外,他汀类药物与改善已有肾脏疾病患者的肾功能或预防新发生的肾功能障碍以及改善慢性阻塞性肺疾病或与年龄相关的肺功能下降患者的肺功能有关。他汀类药物的多效作用似乎是通过改善内皮功能、减少炎症介质、通过稳定粥样斑块来减少动脉粥样硬化的发展以及通过抗氧化机制抑制心肌肥厚来实现的。长期使用他汀类药物可能会降低广泛患者的发病率和死亡率,并且大多数高心血管疾病风险的患者可能会从他汀类药物治疗中获益;然而,需要进一步的数据来明确这些趋势是否确实独立于他汀类药物的降脂作用。

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