Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction
Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction
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DOI：
10.1161/01.cir.104.3.257
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发表时间：
2001-07-17
期刊：
影响因子：
37.8
通讯作者：
Sosman, JM
中科院分区：
文献类型：
--
作者：
Stein, JH;Klein, MA;Sosman, JM
背景-人类免疫缺陷病毒蛋白酶抑制物(HIV PI)与高脂血症、高血糖和肥胖症相关；然而，尚不清楚它们是否会增加动脉粥样硬化性血管疾病的风险。这项研究的目的是描述单纯疱疹病毒感染者使用HIV PI相关的脂蛋白异常，并通过评估这些变化对内皮功能障碍的影响来确定这些变化的病理生理学意义。方法和结果-这是一项对37名接受抗逆转录病毒治疗的HIV-1感染的成年人进行的横断面研究。22人服用HIV PIs(第1组)，15人未服用(第2组)。用酶技术和核磁共振光谱分析测定血脂和脂蛋白。采用高分辨率超声检测肱动脉血流介导的血管扩张功能(FMD)。两组受试者在年龄、被诊断为HIV感染的时间和CD4细胞计数方面相似。第1组总胆固醇(5.68vs4.42mmoL/L，P=0.007)和甘油三酯(4.43vs1.98mmoL/L，P=0.009)水平较高，表现为空腹血糖和极低密度脂蛋白水平升高。第1组受试者FMD2.6+/-4.6%，提示内皮功能明显受损；第2组受试者FMD值正常(8.1+/-6.7%，P=0.005)。在第1组中，乳糜隆、极低密度脂蛋白、IDL和高密度脂蛋白胆固醇水平可预测FMD。结论：HIV PI的使用与致动脉粥样硬化的脂蛋白改变和内皮功能障碍有关。由于这些代谢和血管变化易导致动脉粥样硬化，因此有必要对服用这些药物的患者进行血脂异常的监测和治疗。
Background-Human immunodeficiency virus protease inhibitors (HIV PIs) are associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not known whether they increase risk of atherosclerotic vascular disease. The purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HSV infection and to determine the pathophysiological significance of these changes by assessing their effect on endothelial dysfunction.Methods and Results-This was a cross-sectional study of 37 adults with HIV-1 infection who were receiving antiretroviral therapy. Twenty-two were taking HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins were measured by enzymatic techniques and nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was measured by high-resolution ultrasound. Subjects in both groups were similar in regard to age, time since diagnosis of HIV infection, and CD4 cell count. Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P=0.007) and triglyceride (4.43 versus 1.98 mmol/L, P=0.009) levels, characterized by elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6 +/-4.6%), indicative of significant endothelial dysfunction, Group 2 subjects had normal FMD (8.1 +/- 6.7%, P = 0.005). In group 1, chylomicron, VLDL, IDL, and HDL cholesterol levels predicted FMD.Conclusions-Use of HIV PIs is associated with atherogenic lipoprotein changes and endothelial dysfunction. Because these metabolic and vascular changes predispose to atherosclerosis, monitoring and treatment of dyslipidemia in patients taking these medications is warranted.