Peroxisome proliferator-activated receptor-γ activation with pioglitazone improves endothelium-dependent dilation in nondiabetic patients with major cardiovascular risk factors
Peroxisome proliferator-activated receptor-γ activation with pioglitazone improves endothelium-dependent dilation in nondiabetic patients with major cardiovascular risk factors
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DOI：
10.1161/circulationaha.105.549618
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发表时间：
2006-02-14
期刊：
影响因子：
37.8
通讯作者：
Panza, JA
中科院分区：
文献类型：
--
作者：
Campia, U;Matuskey, LA;Panza, JA
背景--有心血管危险因素的患者存在内皮功能障碍，内皮功能障碍是动脉粥样硬化发病机制中的一个关键因素.噻唑烷二酮类化合物在糖尿病患者中具有多种抗动脉粥样硬化作用。本研究测试的假设，吡格列酮改善非糖尿病患者的主要危险factors.Methods和结果内皮功能-这项研究有一个随机，双盲，安慰剂对照，交叉设计。入组了80例高血压或高胆固醇血症患者。通过定量胰岛素敏感性检查指数（QUICKI）评估胰岛素敏感性，并将患者进一步分类为胰岛素敏感或胰岛素抵抗。在每个治疗阶段，患者接受吡格列酮45 mg每日一次或安慰剂治疗8周。在每8周结束时进行内皮功能和实验室检查。吡格列酮治疗显著降低血浆胰岛素（-22.9%; P < 0.001），QUICKI胰岛素敏感性指数改善（3.7%; P < 0.001），HDL胆固醇升高（8.2%; P < 0.001），甘油三酯（-15.1%; P = 0.003）、游离脂肪酸（-14%; P = 0.005）和C反应蛋白（-28.6%; P = 0.001）减少。吡格列酮治疗显著改善了缓激肽的内皮依赖性舒张（P = 0.01），而不影响对硝普钠的反应（P = 0.31）。在多变量分析中，只有总胆固醇的变化是改善内皮反应性与piglitazone.Conclusions的预测-在非糖尿病患者的心血管危险因素，吡格列酮治疗增强胰岛素敏感性，降低C-反应蛋白，并改善内皮血管舒张功能。这些作用似乎并不密切相关，表明吡格列酮可能具有有益的血管特性，与其对胰岛素敏感性和炎症的作用无关。
Background - Patients with cardiovascular risk factors have endothelial dysfunction, a key element in the pathogenesis of atherosclerosis. The thiazolidinediones have been shown to exert multiple antiatherosclerotic actions in diabetic patients. This study tested the hypothesis that pioglitazone improves endothelial function in nondiabetic patients with major risk factors.Methods and Results - The study had a randomized, double-blind, placebo-controlled, crossover design. Eighty patients with either hypertension or hypercholesterolemia were enrolled. Insulin sensitivity was assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), and patients were further classified as insulin sensitive or insulin resistant. In each treatment phase, patients received either pioglitazone 45 mg daily or placebo for 8 weeks. Endothelial function and laboratory tests were performed at the end of each 8-week period. Treatment with pioglitazone significantly lowered plasma insulin (-22.9%; P < 0.001), improved QUICKI insulin sensitivity index (3.7%; P < 0.001), increased HDL cholesterol (8.2%; P < 0.001), and reduced triglycerides (-15.1%; P = 0.003), free fatty acids (-14%; P = 0.005), and C-reactive protein (-28.6%; P = 0.001). Pioglitazone treatment significantly improved endothelium-dependent dilation to bradykinin (P = 0.01) without affecting the response to sodium nitroprusside (P = 0.31). In multivariable analysis, only changes in total cholesterol were predictors of improved endothelial reactivity with pioglitazone.Conclusions - In nondiabetic patients with cardiovascular risk factors, pioglitazone treatment enhances insulin sensitivity, decreases C-reactive protein, and improves endothelial vasodilator function. These effects do not appear to be closely related, suggesting that pioglitazone may have beneficial vascular properties independent of its effect on insulin sensitivity and inflammation.