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如何平衡他汀类药物对心脏、肾脏和代谢的益处与风险。

How to balance cardiorenometabolic benefits and risks of statins.

作者信息

Lim Soo, Oh Pyung Chun, Sakuma Ichiro, Koh Kwang Kon

机构信息

Division of Endocrinology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.

Cardiology, Gachon University, Gil Medical Center, Incheon, South Korea; Gachon Cardiovascular Research Institute, Incheon, South Korea.

出版信息

Atherosclerosis. 2014 Aug;235(2):644-8. doi: 10.1016/j.atherosclerosis.2014.06.001. Epub 2014 Jun 16.

Abstract

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are important for preventing adverse cardiovascular events not only in patients with a high risk of vascular disease but also in those with a low risk, by reducing the levels of low-density lipoprotein cholesterol. Statin is associated with deteriorating glucose homeostasis and an increased risk of diabetes mellitus. Moreover, these off-target effects are dose-dependent; it has also been suggested that renal insult can be caused dose-dependently by statin treatment, in contrast to previous studies showing a renoprotective effect. The 2013 American College of Cardiology/American Heart Association guidelines recommend the use of high-intensity statin therapy, and extend its use to more people at risk of vascular diseases. However, a European committee has expressed concerns about the potential side effects of using statins in a large fraction of the population for extended periods. This is true of Asian people, for whom the disease burden from cardiovascular disorders is not as great as among Western ethnic groups. There are still many unanswered questions on how to balance the cardiovascular benefits with the potential renometabolic risks of statins. Therefore, genetic or pharmacogenetic approaches are needed to define who is more vulnerable to developing diabetes mellitus or acute kidney injury. In particular, more information is required regarding the metabolism of statins, and their off-target or unknown actions and overall impact. These different renometabolic effects of statins should help in formulating optimal therapeutic strategies for patients for reducing overall morbidity and mortality and not just those associated with cardiovascular diseases.

摘要

他汀类药物,即3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂,不仅对血管疾病高危患者,而且对低危患者预防不良心血管事件都很重要,因为它能降低低密度脂蛋白胆固醇水平。他汀类药物与葡萄糖稳态恶化及糖尿病风险增加有关。此外,这些脱靶效应具有剂量依赖性;与之前显示具有肾脏保护作用的研究相反,也有研究表明他汀类药物治疗可剂量依赖性地导致肾损伤。2013年美国心脏病学会/美国心脏协会指南推荐使用高强度他汀类药物治疗,并将其应用范围扩大到更多有血管疾病风险的人群。然而,一个欧洲委员会对在很大一部分人群中长期使用他汀类药物的潜在副作用表示担忧。亚洲人群也是如此,他们心血管疾病的疾病负担不如西方种族群体那么大。关于如何平衡他汀类药物的心血管益处与潜在的肾脏代谢风险,仍有许多问题未得到解答。因此,需要采用遗传学或药物遗传学方法来确定谁更容易患糖尿病或急性肾损伤。特别是,需要更多关于他汀类药物代谢及其脱靶或未知作用和总体影响的信息。他汀类药物这些不同的肾脏代谢效应应有助于为患者制定最佳治疗策略,以降低总体发病率和死亡率,而不仅仅是与心血管疾病相关的发病率和死亡率。

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