Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus
Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus
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DOI：
10.1210/jc.2007-0393
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发表时间：
2007-07-01
影响因子：
5.8
通讯作者：
Adler, Gail K.
中科院分区：
文献类型：
--
作者：
Joffe, Hylton V.;Kwong, Raymond Y.;Adler, Gail K.
背景：冠状动脉循环功能受损可预测心血管事件，是糖尿病患者死亡的主要原因。醛固酮引起心血管损伤，慢性血管紧张素转换酶（ACE）抑制剂治疗不能抑制醛固酮。目的：我们的目的是评估矿皮质激素受体激活是否会导致已经接受ACE抑制剂治疗的糖尿病患者冠状动脉循环功能障碍。设计和环境：一项随机、双盲、交叉研究，对来自社区的门诊患者进行了至少4周的干预洗脱期。患者：16例患者（男性11例，白种人8例，平均年龄53岁，平均体重指数38.0 kg/ m2），伴有糖尿病和蛋白尿，但无临床心血管疾病。干预措施：ACE抑制剂改为依那普利20mg /天，其他抗高血压药物停用。每天添加氨氯地平5-10毫克，使血压低于130/80毫米汞柱。然后，受试者随机接受矿皮质激素受体拮抗剂依普利酮50毫克（含安慰剂丸），每天6周另一种利尿剂氢氯噻嗪12.5毫克（含钾10 mEq）。主要观察指标：在每6周治疗前后，我们测量了冠状动脉循环功能（腺苷刺激心肌灌注储备）和内皮功能（肱动脉反应性和外周动脉张力测量）。结果：依普利酮组和氢氯噻嗪组血压、血钾、血糖和内皮功能相似。预处理心肌灌注储备组间无差异，但依普利酮组心肌灌注储备显著高于氢氯噻嗪组（中位数1.57 vs. 1.30, P = 0.03）。结论：与氢氯噻嗪相比，矿皮质激素受体阻断剂可改善已接受ACE抑制剂治疗的糖尿病患者的冠状动脉循环功能。
Context: Impaired coronary circulatory function predicts cardiovascular events, the leading cause of death in patients with diabetes mellitus. Aldosterone causes cardiovascular injury and is not suppressed by chronic angiotensin converting enzyme (ACE) inhibitor therapy.Objective: Our objective was to assess whether mineralocorticoid receptor activation contributes to coronary circulatory dysfunction in patients with diabetes who are already receiving ACE inhibitor therapy.Design and Setting: A randomized, double-blind, crossover study with an intervening washout period of at least 4 wk was conducted with ambulatory patients from the community.Patients: Patients included 16 subjects (11 men, eight Caucasians; mean age, 53 yr; mean body mass index, 38.0 kg/ m2) with diabetes and albuminuria but without clinical cardiovascular disease.Interventions: ACE inhibitors were switched to enalapril 20 mg daily, and other antihypertensives were discontinued. Amlodipine 5-10 mg daily was added to achieve blood pressures less than 130/80 mm Hg. Subjects then received, in random order, 6 wk of the mineralocorticoid receptor antagonist eplerenone 50 mg (with placebo pill) daily and 6 wk of another diuretic, hydrochlorothiazide 12.5 mg (with potassium 10 mEq) daily.Main Outcome Measures: Before and after each 6-wk treatment period, we measured coronary circulatory function (adenosine- stimulated myocardial perfusion reserve) and endothelial function (brachial artery reactivity and peripheral arterial tonometry).Results: The eplerenone and hydrochlorothiazide groups had similar blood pressures, serum potassium, glycemia, and endothelial function. Although pretreatment myocardial perfusion reserve did not differ between groups, myocardial perfusion reserve was significantly higher after eplerenone than after hydrochlorothiazide ( median 1.57 vs. 1.30; P = 0.03).Conclusions: Mineralocorticoid receptor blockade improves coronary circulatory function compared with hydrochlorothiazide in patients with diabetes already receiving ACE inhibitor therapy.