Lowering Uric Acid in Normouricaemic Hypertensive Patients Has an Adverse Effect on Left Ventricular Hypertrophy Regression: Mechanistic Proof of the Urate Paradox

C. Gingles, R. Symon, S.j. Gandy, A.d. Struthers, G. Houston, T.m. Macdonald, C.c. Lang, P.t. Donnan, J. George

Research output: Contribution to journalMeeting abstract

Abstract

Objective:
Urate is the most abundant aqueous antioxidant in humans but is pro-oxidant under certain conditions. Allopurinol has been shown to regress left ventricular hypertrophy (LVH) in cohorts with established cardiovascular and cardio-renal disease. This study investigated the impact of lowering urate with allopurinol on LVH regression in a cohort with well controlled essential hypertension, low background levels of inflammation and oxidative stress compared to previous cohorts.

Design and method:
A randomised double-blind, placebo-controlled, parallel group study was conducted in 62 patients with well controlled hypertension and LVH, comparing 600 mg/day allopurinol or placebo therapy for 12 months. The primary outcome was change in left ventricular mass (LVM) as assessed by cardiac MRI. Secondary outcomes were changes in biomarkers of oxidative stress (Thiobarbituric acid reactive substances (TBARs)), endothelial function assessed by flow-mediated dilatation (FMD) and arterial stiffness by applanation tonometry.

Results:
LVH regression was significantly attenuated in the allopurinol cohort compared to placebo (indexed LVM −0.18 ± 2.39 g/m1.7 vs −1.60 ± 1.60 g/m1.7; p = 0.009). Oxidative stress markers (TBARs) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs −0.34 ± 0.83uM; p = 0.007). Blood pressures and all other markers of vascular function was not significantly different between the two groups.

Conclusions:
In patients with well controlled hypertension and LVH, allopurinol induced urate reduction results in reduced LVH regression and increased oxidative stress compared to placebo. Reducing urate in normouricaemic patients with hypertension and LVH adversely impacts on redox balance and LVH regression.
Original languageEnglish
Pages (from-to)e57
JournalJournal of Hypertension
Volume37
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint Dive into the research topics of 'Lowering Uric Acid in Normouricaemic Hypertensive Patients Has an Adverse Effect on Left Ventricular Hypertrophy Regression: Mechanistic Proof of the Urate Paradox'. Together they form a unique fingerprint.

  • Profiles

    No photo of Graeme Houston

    Houston, Graeme

    Person: Academic

    Cite this