缬沙坦阻断血管紧张素II 1型受体对颈动脉粥样硬化的影响：一项比较缬沙坦与安慰剂的双盲随机临床试验（EFFERVESCENT）。
Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).
作者信息
Ramadan Ronnie, Dhawan Saurabh S, Binongo José Nilo G, Alkhoder Ayman, Jones Dean P, Oshinski John N, Quyyumi Arshed A
机构信息
Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
出版信息
Am Heart J. 2016 Apr;174:68-79. doi: 10.1016/j.ahj.2015.12.021. Epub 2016 Jan 18.
BACKGROUND
Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis.
METHODS
Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function.
RESULTS
Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function.
CONCLUSIONS
In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.
背景
动脉粥样硬化的进展与不良后果风险增加相关。血管紧张素II在动脉粥样硬化的发病机制和进展中起关键作用。我们旨在研究缬沙坦阻断血管紧张素II 1型受体对颈动脉壁动脉粥样硬化的影响，假设缬沙坦将减少动脉粥样硬化的进展。
方法
通过超声检查发现颈动脉内膜中层厚度>0.65 mm的受试者（n = 120）以2:1的比例被随机分为两组，双盲接受缬沙坦或安慰剂治疗2年。在基线、12个月和24个月时进行双侧T2加权黑血颈动脉磁共振成像。颈动脉球血管壁面积和壁厚的变化是主要终点。次要终点包括颈动脉斑块厚度、血浆氨基硫醇、C反应蛋白、纤维蛋白原水平以及内皮依赖性和非内皮依赖性血管功能的变化。
结果
在2年期间，缬沙坦组的颈动脉球血管壁面积减少（-6.7，95%可信区间[-11.6，-1.9]mm²），而安慰剂组未减少（3.4，95%可信区间[-2.8，9.6]mm²），两组间P = 0.01。同样，缬沙坦组的平均壁厚减少（-0.18，95%可信区间[-0.30，-0.06]mm），而安慰剂组未减少（0.08，95%可信区间[-0.07，0.23]mm），两组间P = 0.009。此外，缬沙坦组的斑块厚度减少（-0.35，95%可信区间[-0.63，-0.08]mm），而安慰剂组无变化（+0.28，95%可信区间[-0.11，0.69]mm），两组间P = 0.01。这些发现不受他汀类药物治疗或血压变化的影响。值得注意的是，氨基硫醇半胱氨酸谷胱甘肽二硫化物有显著改善趋势，纤维蛋白原水平和非内皮依赖性血管功能也有改善趋势。
结论
在颈动脉壁增厚的受试者中，血管紧张素II 1型受体阻断与颈动脉粥样硬化的消退相关。这些作用是否能转化为亚临床动脉粥样硬化受试者的预后改善尚需研究。
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