Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries - A randomized, double-blind, placebo-controlled study
Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries - A randomized, double-blind, placebo-controlled study
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DOI：
10.1016/j.jacc.2006.04.088
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发表时间：
2006-09-05
影响因子：
24
通讯作者：
Sattar, Naveed
中科院分区：
文献类型：
--
作者：
Jadhav, Sachin;Ferrell, William;Sattar, Naveed
目的本研究旨在确定二甲双胍是否能改善非糖尿病患者的血管功能或心肌缺血。背景二甲双胍可预防糖尿病，并可减少糖尿病患者的冠状动脉事件，但对微血管功能和心绞痛的影响尚不清楚。方法我们对33名既往冠状动脉造影史正常但连续两次运动耐量试验阳性(ST段压低1 mm)的非糖尿病女性进行了为期8周的双盲、随机、安慰剂对照研究。在基线和8周时测量所有参数，并使用激光多普勒成像结合离子导入技术在体内评估前臂(皮肤)微血管功能。结果与安慰剂组(n=17)相比，二甲双胍组(n=16)的体重和胰岛素抵抗的稳态模型评估均显著减轻(p<；0.05，意向治疗)。血管内皮依赖性微血管反应用二甲双胍显著改善(双向重复方差分析，p=0.0003)，而用安慰剂的反应不变(p=0.5)。无论是通过双因素方差分析(p<；0.0001)还是曲线下面积的变化(平均变化+392灌流单位，95%可信区间[CI]20至764)，二甲双胍和安慰剂接受者之间的乙酰胆碱反应变化的比较是显著的。非内皮依赖性反应未发生改变。与安慰剂组相比，二甲双胍组的最大ST段压低(-0.84 mm，95%CI-1.49~-0.20，p=0.013)、Duke评分(6.1U，95%CI 1.8~10.5，p=0.008)和胸痛发生率(-0.11次/天，95%CI-0.22~0.00，p=0.056)均有改善。有必要进行更大规模、持续时间更长的对照试验。
OBJECTIVES This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects.BACKGROUND Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear.METHODS We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression >= 1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis.RESULTS In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [Cl] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% Cl -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% Cl 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients.CONCLUSIONS Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.