CIRCADIAN VARIATION OF ACUTE MYOCARDIAL-INFARCTION AND THE EFFECT OF LOW-DOSE ASPIRIN IN A RANDOMIZED TRIAL OF PHYSICIANS
CIRCADIAN VARIATION OF ACUTE MYOCARDIAL-INFARCTION AND THE EFFECT OF LOW-DOSE ASPIRIN IN A RANDOMIZED TRIAL OF PHYSICIANS
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DOI：
10.1161/01.cir.82.3.897
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发表时间：
1990-09-01
期刊：
影响因子：
37.8
通讯作者：
HENNEKENS, CH
中科院分区：
文献类型：
--
作者：
RIDKER, PM;MANSON, JE;HENNEKENS, CH
早晨和直立姿势时血小板聚集增加，可能至少部分解释了观察到的急性心肌梗死发病的昼夜变化。《内科医生健康研究》是一项随机、双盲、安慰剂对照试验，对22071名美国男性医生进行了隔天服用阿司匹林（325毫克）的研究，为评估这种昼夜节律模式提供了机会，并检查阿司匹林治疗是否会改变这种模式。在5年随访期间，确诊非致死性心肌梗死342例，其中211例（62%）可查到发病时间。安慰剂组心肌梗死发病呈双峰性昼夜变化，在凌晨4点至10点之间出现主要高峰（p < 0.001）。然而，在阿司匹林组中，这种昼夜变化最小（p = 0.16），主要是由于梗死的早晨高峰明显减少。具体来说，在早晨醒着的时间内，阿司匹林与梗死发生率降低59.3%相关，而在一天的剩余时间内，阿司匹林的发生率降低34.1%。在醒来后的3小时间隔中观察到更大的降低，这段时间的梗死风险是任何其他可比时间间隔的两倍（p < 0.001）。在整个24小时周期内，阿司匹林摄入量与梗死发生率平均降低44.8%相关。这些数据支持了一种假设，即早晨和起床时血小板聚集性的增加有助于心肌梗死的发生，而阿司匹林通过抑制这些关键时期的血小板聚集来降低梗死的风险。
Increased platelet aggregation in the morning and upon assuming an upright posture may account at least in part for the observed circadian variation in onset of acute myocardial infarction. The Physicians'' Health Study, a randomized, double-blind placebo-controlled trial of alternate-day aspirin intake (325 mg) among 22,071 US male physicians, afforded the opportunity to assess this circadian pattern and examine whether it is altered by aspirin therapy. During a 5-year period of follow-up, 342 cases of nonfatal myocardial infarction were confirmed, of which the time of onset was available in 211 (62%). The placebo group showed a bimodal circadian variation in onset of myocardial infarction with a primary peak between 4:00 AM and 10:00 AM (p < 0.001). In the aspirin group, however, this circadian variation was minimal (p = 0.16), due primarily to a marked reduction in the morning peak of infarction. Specifically, aspirin was associated with a 59.3% reduction in the incidence of infarction during the morning waking hours, compared with a 34.1% reduction for the remaining hours of the day. The greater reduction was observed during the 3-hour interval immediately after awakening, a period with a risk of infarction twice that of any other comparable time interval (p < 0.001). Aspirin intake was associated with a mean reduction in the incidence of infarction of 44.8% over the entire 24-hour cycle. These data support the hypothesis that increased platelet aggregability in the morning and upon arising contributes to the occurrence of myocardial infarction and that aspirin reduces the risk of infarction by inhibiting platelet aggregation during these critical periods.