Abstract 14498: Allopurinol Reduces Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiorenal Patients
Introduction: Left ventricular hypertrophy (LVH) and vascular dysfunction are key pathophysiological processes that lead to cardiovascular (CV) events in patients with chronic kidney disease (CKD). As oxidative stress is thought to contribute to both LVH and endothelial dysfunction in CKD, we hypothesized that allopurinol might regress left ventricular (LV) mass and improve endothelial dysfunction and arterial stiffness in CKD patients.
Methods: A randomised, double-blind, placebo-controlled, parallel study was conducted in patients with CKD stage 3 and LVH. Subjects received 300mg/day Allopurinol or placebo for 9 months. Cardiac magnetic resonance (CMR) was performed to measure LV mass index (LVMI). Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery, while central arterial stiffness was assessed by pulse wave analysis (PWA) and pulse wave velocity (PWV).
Results: 53 patients completed the study (27 active, 26 placebo). Allopurinol significantly reduced LVH [ΔLVMI: −1.42±4.67g/m2, allopurinol vs +1.28±4.45g/m2, placebo (p=0.036)]. Allopurinol also significantly improved brachial artery FMD [ΔFMD: +1.26± 3.06%, allopurinol vs −1.05± 2.84%, placebo (p=0.009)]. Central augmentation index (AIx) also improved significantly on allopurinol [ΔAIx: −4.70±9.30%, allopurinol vs +0.77±6.06%, placebo (p=0.015)]. There was also a trend towards improvement in PWV in patients on allopurinol [ΔPWV was −0.39 ± 1.13 m/s, allopurinol vs and +0.20 ± 1.28 m/s, placebo (P=0.086)].
Conclusion: This is the first study to demonstrate that allopurinol can regress LV mass in any population and the first to demonstrate that it improves endothelial dysfunction in CKD patients. As LVH and endothelial dysfunction are both important surrogate markers for prognosis, this study should prompt future trials to examine whether allopurinol reduces CV events in CKD patients with LVH.
- © 2010 by American Heart Association, Inc.