Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.
Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.
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DOI：
10.1161/hypertensionaha.116.08488
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Forman JP
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文献类型：
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作者：
Borgi L;McMullan C;Wohlhueter A;Curhan GC;Fisher ND;Forman JP
高水平的血清尿酸与内皮功能障碍独立相关，内皮功能障碍是高血压发生的机制之一。肥胖/超重的人比瘦弱的人更容易发生内皮功能障碍。然而，降低血清尿酸对这些个体内皮功能障碍的影响尚未得到彻底的研究。在这项随机、双盲、安慰剂对照试验中，研究对象为血清尿酸较高的非高血压、超重或肥胖个体（体重指数≥25 kg/m2，血清尿酸≥5.0 mg/dL），我们给受试者分配了probenecid （500 - 1000mg/天）、别嘌呤醇（300 - 600mg/天）或匹配的安慰剂。主要结局是在基线和8周时通过肱动脉超声测量内皮依赖性血管舒张。到试验结束时，分别有47名、49名和53名参与者被分配到服用丙戊酸、别嘌呤醇和安慰剂组。在丙戊酸组（从6.1到3.5 mg/dL）和别嘌呤醇组（从6.1到2.9 mg/dL）中，平均血清尿酸水平显著降低，但在安慰剂组（从6.1到5.6 mg/dL）中没有显著降低。所有干预措施均未对内皮依赖性血管舒张产生任何显著改变（probenecid，基线值为7.4±5.1%，8周时为8.3±5.1%；别嘌呤醇，基线值为7.6±6.0%，8周时为6.2±4.8%；安慰剂，基线值为6.5±3.8%，8周时为7.1±4.9%）。在这项随机、双盲、安慰剂对照试验中，降低尿酸对超重或肥胖非高血压患者的内皮功能没有影响。这些数据不支持尿酸与内皮功能障碍有因果关系的假设，而内皮功能障碍是高血压发生的潜在机制。
Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Obese/overweight individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight or obese individuals with higher serum uric acid (body mass index≥25 kg/m2 and serum uric acid≥5.0 mg/dL), we assigned subjects to probenecid (500 to 1000mg/day), allopurinol (300 to 600mg/day), or matching placebo. The primary outcome was endothelial-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49 and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL), but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelial-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not impact endothelial function in overweight or obese non-hypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension.