Ezetimibe Monotherapy Ameliorates Vascular Function in Patients with Hypercholesterolemia Through Decreasing Oxidative Stress
Ezetimibe Monotherapy Ameliorates Vascular Function in Patients with Hypercholesterolemia Through Decreasing Oxidative Stress
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DOI：
10.5551/jat.9548
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Kitagawa, Tetsuya
中科院分区：
文献类型：
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作者：
Kurobe, Hirotsugu;Aihara, Ken-ichi;Kitagawa, Tetsuya
目的：依折麦布是一种胆固醇肠吸收抑制剂，是一种降脂药。然而，依折麦布的抗动脉粥样硬化作用尚未完全阐明。因此，本研究的目的是阐明依折麦布在高胆固醇血症患者中的血管保护作用。方法：依折麦布治疗20例高胆固醇血症患者（E组），20例年龄和性别匹配的高胆固醇血症患者作为对照组（C组）。依折麦布治疗前和依折麦布治疗12周后的代谢特征和心血管替代标志物的差异进行了统计学评估。结果：依折麦布治疗显着降低血清低密度脂蛋白胆固醇（LDL-C）和丙二醛修饰的低密度脂蛋白（MDA-LDL）水平。与C组相比，E组体重指数、体重、腰围、血浆HbA 1c和尿白蛋白均显著降低。另一方面，与C组相比，E组的高密度脂蛋白胆固醇（HDL-C）和脂联素水平显著升高。E组的臂踝脉搏波传导速度（ba-PWV）、平均动脉血压（m-ABP）和血流介导的舒张功能（FMD）百分比均明显改善。超声检查显示，E组颈总动脉血管僵硬度改善，而C组无此改变。依折麦布的这些血管保护作用与MDA-LDL和MDA-LDL-to-LDL-C比值的降低值具有统计学相关性，但与LDL-C的降低值无关。结论：依折麦布通过降低氧化应激对高胆固醇血症患者具有降脂非依赖性血管保护作用。
Aim: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia.Methods: Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age-and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated.Results: Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C.Conclusion: Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.