Effect of Uric Acid–Lowering Agents on Endothelial Function

Abstract

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.

Android Fat Deposition and Its Association With Cardiovascular Risk Factors in Overweight Young Males

“…Hyperuricemia is strongly associated with an increased risk of atherosclerosis and UA has also been shown to induce vascular endothelial dysfunction via oxidative stress and inflammatory responses (Puddu et al, 2012). However, whether elevated UA in the group of young males with high levels of android fat affects their endothelial function is uncertain because lowering UA fails to improve endothelial function (Borgi et al, 2017).…”

Markers of endothelial injury and subclinical inflammation in children and adolescents with primary hypertension

“…There remains an unanswered question, whether lowering uric acid can reverse the negative phenomena observed in PH, including endothelial injury. Feig showed that treatment with allopurinol can normalise blood pressure in hypertensive adolescents [25], but a recently published trial failed to prove a beneficial role of allopurinol in normalisation of endothelial dysfunction in adults with PH [26].…”

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

“…A few RCTs assessing the impact of uric acid lowering drugs on parameters of endothelial function showed no positive effect [ 155 , 156 ]. On the other hand, in a short-term study, allopurinol was shown to decrease blood pressure in young adolescents with newly diagnosed essential hypertension [ 157 ].…”