Abstract
Introduction:
Endothelial dysfunction is a precursor of atherosclerosis, and has been found to be present in patients with diabetes, hypertension, hypercholesterolemia, smoking habit, obstructive sleep apnea, hyperuricemia and chronic kidney disease. Measurement of endothelial function by either flow-mediated dilatation (FMD) or forearm venous-occlusion plethysmography (FVOP) of brachial artery has been previously validated. Allopurinol is a xanthine oxidase inhibitor that has been shown to correct endothelial dysfunction in coronary artery disease, congestive heart failure and hypertension by different mechanisms. We conducted a meta-analysis of all available randomized controlled trials (RCTs) that studied the effect of allopurinol in endothelial dysfunction as measured by FMD or FVOP of brachial artery.
Methods:
We performed literature search with predefined criteria with "allopurinol" and "endothelial function" or "endothelial dysfunction" in PubMed, Cochrane Database, EMBASE and proceedings from various society meetings through December 15, 2011. Only the RCTs that compared the effect of allopurinol with placebo on endothelial dysfunction in patients with proven risk factors for endothelial dysfunction were included in the analysis. Random Effects Model was used for analysis of the data using software MetaAnalyst Beta 3.13 (Tufts, Boston, USA).
Results:
A total of 10 RCTs with 519 patients were included in the analysis.When compared to placebo, allopurinol improved the endothelial dysfunction as measured by FMD or FVOP (pooled mean difference 2.335, 95% CI = 1.46 - 3.21, p <0.05, I2 = 98%). The heterogeneity of data was due to different disease conditions, dose and duration of allopurinol and the methods of measurement of endothelial dysfunction.
Conclusion:
We conclude that allopurinol improves endothelial dysfunction in patients with various cardiovascular risk factors. Allopurinol may have a role in preventing atherosclerosis in patients with various cardiovascular risk factors for endothelial dysfunction.