Abstract 13446: High Dose Allopurinol Improves Endothelial Dysfunction iPatients with Ischemic Heart Disease and Left Ventricular Hypertrophy but Does Not Match Age and Gender Matched Controls
Background Endothelial dysfunction occurs commonly in patients with ischemic heart disease and is known to be a poor prognostic risk marker for mortality and cardiovascular events. Oxidative stress plays a pathophysiological role in the development of endothelial dysfunction. Xanthine oxidase is an enzyme that generates superoxide free radicals. Hence, we hypothesized that high dose allopurinol, a xanthine oxidase inhibitor, improves endothelial dysfunction to match age and gender matched healthy volunteers.
Methods Sixty-six patients with ischemic heart disease and left ventricular hypertrophy were recruited into a randomized, double blind, placebo controlled parallel study. They received 600mg/day allopurinol or placebo therapy over a nine month follow up period. Endothelial function tests were performed at baseline, six months and nine months visit. In addition, thirty age and gender matched healthy volunteers (HV) attended a single study visit for endothelial function tests. Endothelial function was assessed using flow-mediated dilatation (FMD) of the brachial artery and arterial stiffness measured using pulse wave analysis.
Results Sixty patients completed the main study (31 active, 29 placebo). At baseline, the HV had a significantly greater FMD and lower AIx compared to the allopurinol group. Allopurinol significantly improved brachial artery FMD [ΔFMD: + 0.82% ±1.8% allopurinol vs - 0.69% ±2.8% placebo; p= 0.017] and central augmentation index [Δ AIx: -2.8% ± 5.1% allopurinol vs +0.9% ± 7% placebo; p=0.02]. However, after nine months of allopurinol therapy, their absolute endothelial function did not match that of age and gender matched normals [FMD: 4.94 ±2.2 % allopurinol vs 6.3 ±3.74% HV, p=0.092; AIx: 17.4 ±8.6% vs 12.8 ±11% HV, p=0.071].
Conclusions In conclusion, high dose allopurinol improves endothelial dysfunction in patients with ischemic heart disease and left ventricular hypertrophy but their absolute endothelial function does not match age and gender matched normals.
- © 2012 by American Heart Association, Inc.