National Heart Centre Singapore, Singapore, Singapore.
Aberdeen Royal Infirmary, Aberdeen, Scotland.
Cardiovasc Ther. 2018 Feb;36(1). doi: 10.1111/1755-5922.12311. Epub 2017 Nov 26.
The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this "proof of concept" study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B-type natriuretic peptide (BNP: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X.
This study was a randomized, double-blind, placebo-control crossover trial. Nineteen patients (mean age 59 ± 10 years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6-week treatment with either allopurinol (600 mg/day) or placebo. After 4 weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET) derived from Bruce protocol exercise treadmill test, serum BNP measurement, coronary flow reserve (CFR) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow-mediated vasodilatation of the brachial artery (FMD). Allopurinol significantly reduced serum uric acid levels when compared with placebo (-48 ± 24% vs 1.9 ± 11%, P < .001). There was no significant difference in maximum ET, CFR, and FMD between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP when compared to placebo (-8% [interquartile range -22% to 65%] vs 44% [interquartile range -18% to 140%]; P = .07).
In patients with cardiac syndrome X, high-dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.
最近认识到内皮功能障碍和氧化应激在心脏 X 综合征发病机制中的作用。别嘌醇先前已被证明可改善内皮功能障碍、降低氧化应激负担和提高心肌效率。在这项“概念验证”研究中，我们研究了别嘌醇对心脏 X 综合征患者的运动能力、冠状动脉和外周内皮功能以及血清 B 型利钠肽（BNP：心脏功能和心肌缺血的标志物）的影响。
这是一项随机、双盲、安慰剂对照交叉试验。19 名（平均年龄 59±10 岁，11 名女性和 8 名男性）心脏 X 综合征患者被随机分为别嘌醇（600mg/天）或安慰剂治疗 6 周。经过 4 周洗脱期后，他们交叉到另一组。在基线和治疗后测量的结果是 Bruce 方案跑步机运动试验得出的最大运动时间（ET）、血清 BNP 测量值、通过测量左前降支血流速度对腺苷的反应评估的冠状动脉血流储备（CFR）以及肱动脉血流介导的血管舒张（FMD）。与安慰剂相比，别嘌醇显著降低了血清尿酸水平（-48±24%对 1.9±11%，P<.001）。别嘌醇与安慰剂之间的最大 ET、CFR 和 FMD 无显著差异。然而，与安慰剂相比，别嘌醇有降低血清 BNP 的趋势（-8%[四分位距-22%至 65%]对 44%[四分位距-18%至 140%]；P=0.07）。
在心脏 X 综合征患者中，高剂量别嘌醇不能改善运动能力以及冠状动脉或外周内皮功能。
