Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension
Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension
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DOI：
10.1097/hjh.0000000000002189
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发表时间：
2019-12-01
影响因子：
4.9
通讯作者：
George, Jacob
中科院分区：
文献类型：
--
作者：
Gingles, Christopher R.;Symon, Ruth;George, Jacob
目的：先前的研究表明，高剂量别嘌呤醇能够使已患有心血管疾病的人群的左心室 (LV) 质量消退。本研究的目的是评估高剂量别嘌呤醇治疗是否会在原发性高血压、左心室肥厚和血压控制良好但没有明确心血管疾病的队列中使左心室质量消退。方法：我们进行了别嘌呤醇（600 mg/天）与安慰剂对左心室质量消退的机械概念验证随机、安慰剂对照、双盲试验。治疗持续时间为12个月。通过心脏磁共振评估左心室质量消退。次要结局是内皮功能（血流介导的扩张）、动脉僵硬度（脉搏波速度）和氧化应激生物标志物的变化。 结果：72 名患者被随机分配进入试验。平均基线尿酸为 362.2 +/- 96.7 mumol/l。尽管血压控制良好，但与安慰剂相比，别嘌呤醇组的左心室质量退化显着减少（左心室质量 -0.37 +/- 6.08 与 -3.75 +/- 3.89g；P= 0.012）。别嘌呤醇组的氧化应激标志物（硫代巴比妥酸反应物质）显着高于安慰剂组（0.26 +/- 0.85 vs -0.34 +/- 0.83 mu mol/l；P=0.007）。两组之间其他血管功能标志物没有显着差异。 结论：对于血尿酸正常且左心室肥厚的高血压患者，使用大剂量别嘌呤醇治疗是有害的。它会导致 12 个月内左室质量退化减少并增加氧化应激。这可能是因为对氧化还原平衡的不利影响。未来别嘌呤醇心血管试验的队列选择至关重要。
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 randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/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: Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2 +/- 96.7 mu mol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass -0.37 +/- 6.08 versus -3.75 +/- 3.89g; P= 0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26 +/- 0.85 versus -0.34 +/- 0.83 mu mol/l; P=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusion: Treatment with high-dose allopurinol in normouricemic 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 because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.