Stein James H
Section of Cardiovascular Medicine, University of Wisconsin Medical School, Clinical Science Center, Madison, WI 53792, USA.
Prog Cardiovasc Dis. 2003 Jan-Feb;45(4):293-304. doi: 10.1053/pcad.2003.4.
Human immunodeficiency virus protease inhibitors are associated with metabolic abnormalities that may increase risk of atherosclerotic vascular disease, including dyslipidemia, insulin resistance, and central obesity. Dyslipidemia, characterized by hypercholesterolemia and hypertriglyceridemia, small low- and high-density lipoprotein particles, and in some cases lipoprotein(a) excess, can be severe and has been associated with endothelial dysfunction and carotid atherosclerosis. The mechanisms underlying protease inhibitor-associated dyslipidemia have not been elucidated completely, but appear to involve hepatic overproduction of very low-density lipoproteins and to a lesser extent, impaired clearance. Insulin resistance appears to mediate part of the adverse lipoprotein changes observed in patients taking protease inhibitors. Ongoing epidemiological and surrogate endpoint studies are investigating the atherogenicity of these medications. Until the risk associated with use of protease inhibitors is better understood, identifying patients at high risk for adverse vascular events such as heart attacks, cardiac death, and stroke is a high priority. This article reviews the lipid and lipoprotein abnormalities associated with use of protease inhibitors, possible mechanisms for protease inhibitor-associated dyslipidemia, its potential atherogenicity, and use of the National Cholesterol Education Program Adult Treatment Panel III Guidelines for the management of patients with dyslipidemia.
人类免疫缺陷病毒蛋白酶抑制剂与代谢异常有关，这些异常可能增加动脉粥样硬化性血管疾病的风险，包括血脂异常、胰岛素抵抗和中心性肥胖。血脂异常的特征为高胆固醇血症和高甘油三酯血症、低密度和高密度脂蛋白颗粒较小，在某些情况下还伴有脂蛋白(a)过多，可能较为严重，且与内皮功能障碍和颈动脉粥样硬化有关。蛋白酶抑制剂相关血脂异常的潜在机制尚未完全阐明，但似乎涉及肝脏极低密度脂蛋白的过度生成，在较小程度上还涉及清除受损。胰岛素抵抗似乎介导了服用蛋白酶抑制剂患者中观察到的部分不良脂蛋白变化。正在进行的流行病学和替代终点研究正在调查这些药物的致动脉粥样硬化性。在更好地了解与使用蛋白酶抑制剂相关的风险之前，识别有心脏病发作、心源性死亡和中风等不良血管事件高风险的患者是当务之急。本文综述了与使用蛋白酶抑制剂相关的脂质和脂蛋白异常、蛋白酶抑制剂相关血脂异常的可能机制、其潜在的致动脉粥样硬化性，以及使用美国国家胆固醇教育计划成人治疗小组第三次指南管理血脂异常患者的情况。
