Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial

Objective To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. Methods 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. Results 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. Conclusion 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.