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.
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 language | English |
|---|---|
| Pages (from-to) | e57 |
| Journal | Journal of Hypertension |
| Volume | 37 |
| DOIs | |
| Publication status | Published - 1 Jul 2019 |
