University of Alabama at Birmingham and Birmingham VA Medical Center.
University of Alabama at Birmingham.
Arthritis Rheumatol. 2021 Aug;73(8):1514-1522. doi: 10.1002/art.41749. Epub 2021 Jun 5.
To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect.
We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed.
Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events.
Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.
确定别嘌醇降低血尿酸是否能降低年轻成年人的血压（BP）以及介导这种假设效果的机制。
我们进行了一项单中心、随机、双盲、交叉临床试验。纳入的对象为年龄在 18-40 岁之间，基线收缩压≥120mmHg 且<160mmHg，或舒张压≥80mmHg 且<100mmHg，且血清尿酸男性≥5.0mg/dl 或女性≥4.0mg/dl 的成年人。主要排除标准包括慢性肾脏病、痛风或既往使用降尿酸治疗。参与者接受为期 1 个月的口服别嘌醇（300mg 每日）或安慰剂治疗，然后进行 2-4 周的洗脱期，再进行交叉治疗。研究的结果测量指标为收缩压从基线的变化、内皮功能估计为血流介导的扩张（FMD）和高敏 C 反应蛋白（hsCRP）水平。评估了不良事件。
99 名参与者被随机分组，82 名完成了所有访视。平均年龄±标准差为 28.0±7.0 岁，62.6%为男性，40.4%为非裔美国人。在主要的意向治疗分析中，在别嘌醇治疗阶段收缩压没有变化（平均±SEM-1.39±1.16mmHg）或安慰剂治疗阶段（-1.06±1.08mmHg）。与安慰剂治疗期相比，FMD 在别嘌醇治疗期增加（平均±SEM2.5±0.55%对-0.1±0.42%；P<0.001）。hsCRP 水平没有变化，也没有严重的不良事件。
我们的研究结果表明，与安慰剂相比，别嘌醇降低尿酸治疗并不能降低年轻成年人的收缩压或 hsCRP 水平，尽管 FMD 有所改善。这些发现不支持将降低尿酸作为年轻成年人高血压的治疗方法。
