Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

Christopher Gingles, Ruth Symon, Stephen Gandy, Allan Struthers, Graeme Houston, Thomas MacDonald, Chim Lang, Peter Donnan, Jacob George (Lead / Corresponding author)

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Abstract

Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.

Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress.

Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.

Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.
Original languageEnglish
Pages (from-to)2481-2489
Number of pages9
JournalJournal of Hypertension
Volume37
Issue number12
Early online date1 Jul 2019
DOIs
Publication statusPublished - Dec 2019

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Allopurinol
Hypertension
Placebos
Oxidative Stress
Left Ventricular Hypertrophy
Therapeutics
Cardiovascular Diseases
Blood Pressure
Pulse Wave Analysis
Vascular Stiffness
Thiobarbituric Acid Reactive Substances
Uric Acid
Oxidation-Reduction
Blood Vessels
Dilatation
Magnetic Resonance Spectroscopy
Biomarkers

Keywords

  • Uric acid
  • oxidative stress
  • hypertension

Cite this

@article{39944988790c4116b4708e890db621fa,
title = "Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension",
abstract = "Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.",
keywords = "Uric acid, oxidative stress, hypertension",
author = "Christopher Gingles and Ruth Symon and Stephen Gandy and Allan Struthers and Graeme Houston and Thomas MacDonald and Chim Lang and Peter Donnan and Jacob George",
note = "This study was funded by a grant from the British Heart Foundation (PG/13/67/30444).",
year = "2019",
month = "12",
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language = "English",
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pages = "2481--2489",
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Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension. / Gingles, Christopher; Symon, Ruth; Gandy, Stephen; Struthers, Allan; Houston, Graeme; MacDonald, Thomas; Lang, Chim; Donnan, Peter; George, Jacob (Lead / Corresponding author).

In: Journal of Hypertension, Vol. 37, No. 12, 12.2019, p. 2481-2489.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

AU - Gingles, Christopher

AU - Symon, Ruth

AU - Gandy, Stephen

AU - Struthers, Allan

AU - Houston, Graeme

AU - MacDonald, Thomas

AU - Lang, Chim

AU - Donnan, Peter

AU - George, Jacob

N1 - This study was funded by a grant from the British Heart Foundation (PG/13/67/30444).

PY - 2019/12

Y1 - 2019/12

N2 - Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

AB - Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.

KW - Uric acid

KW - oxidative stress

KW - hypertension

U2 - 10.1097/HJH.0000000000002189

DO - 10.1097/HJH.0000000000002189

M3 - Article

C2 - 31268872

VL - 37

SP - 2481

EP - 2489

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 12

ER -