MODIFIERS OF MYOCARDIAL INFARCTION ONSET

这是一个修改后的竞争性续期申请进行研究 标题为“心肌梗死发作的修饰物（修饰物研究）”， 阐明急性心肌梗死（MI）的病理生理学 发病我们将利用方法学技术，50家医院 国家研究小组，以及已完成的NHLBL资助的 心肌梗死发病的决定因素研究（决定因素研究）。 修改者研究将确定增加或减少 患者对急性心肌梗塞触发因素的敏感性 以前识别的。 决定因素研究开始于1989年，在广泛传播之后不久， 接受MI发生的昼夜变化。这项研究是 开始利用最先进的流行病学技术， 确定日常活动在MI触发中的作用。的 研究人员创造了一种新的流行病学技术（病例交叉 方法），开发和测试了一个24页的面试表， 由经过培训的访问者组成的大型医院研究小组， 质量控制措施，并招募了2,000多名受试者。这 广泛的活动使决定因素研究成为 发展对急性疾病发作触发的研究领域。 决定因素研究实现了其四个具体目标。它 证明了觉醒/活动，而不是绝对的时间 白天，负责早晨的触发，繁重的工作，愤怒， 和性活动是Ml的触发因素，相对风险为6，3， 2分别，β-阻断防止触发， 觉醒/活动，久坐的生活方式显着增加 重度劳累引发心肌梗塞的相对风险。 拟议的修改量研究将回答 决定因素研究的结果。它将检验假设 关于5组因素，这些因素是 对急性MI触发的敏感性：l）药理学手段 β受体阻滞剂，阿司匹林，血管紧张素转换 酶抑制剂和雌激素的使用降低了对触发物的敏感性; 2)时间-易感性在早上不会增加， 在冬天，外源性而不是内源性的日常生活 节律决定发病; 3）传统的慢性风险因素- 糖尿病、高血压和吸烟会增加易感性， 定期锻炼可降低敏感性（除 4）性别-女性较不易受到触发; 和5）饮食因素-慢性适度饮酒和抗- 氧化剂降低易感性。 为了验证上述假设，需要进行5，700次访谈。由 1993年3月完成决定因素研究后， 面试将完成。 “的”修饰语研究的延续 我们目前每月77次面试将提供所需的3700个 1997年12月前进行更多访谈。为了保持研究 在8个月的修改研究审查期间，我们将 用有限非联邦资金支持护士面试。 拟议研究的长期目标是更全面地确定 触发发生的机制，从而促进 确定新的预防手段。虽然大多数潜在的 触发活动是不可避免的，急性MI的触发可能 通过使用药物或其他干预措施来预防， 潜在诱因与其灾难性后果之间的生理联系 后果

This is a revised competing renewal application to conduct a study entitled Modifiers of Myocardial Infarction Onset (Modifiers Study) to elucidate the pathophysiology of acute myocardial infarction (Ml) onset. We will utilize the methodologic techniques, 50-hospital national study group, and findings of the completed NHLBl-funded Determinants of Myocardial Infarction Onset Study (Determinants Study). The Modifiers Study will identify factors that increase or decrease the susceptibility of patients to the triggers of acute Ml we have previously identified. The Determinants Study began in 1989, shortly after widespread acceptance of the circadian variation in Ml occurrence. The study was initiated to utilize state-of-the art epidemiologic techniques to determine the role of daily activities in the triggering of Ml. The investigators created a new epidemiologic technique (the case-crossover method), developed and tested a 24-page interview form established a large study group of hospitals with trained interviewers, instituted quality control measures, and enrolled over 2,000 subjects. This extensive activity has made the Determinants Study a centerpiece in the developing field of research into triggering of acute disease onset. The Determinants Study accomplished its four Specific Aims. It demonstrated that awakening/activity, rather than the absolute time of day, is responsible for morning triggering, that heavy exertion, anger, and sexual activity are triggers of Ml with relative risks of 6, 3, and 2 respectively, that beta-blockade prevents triggering by awakening/activity, and that a sedentary lifestyle markedly increases the relative risk of triggering of Ml by heavy exertion. The proposed Modifiers Study will answer the major questions raised by the results of the Determinants Study. It will test hypotheses concerning 5 groups of factors that are potential modifiers of susceptibility to the triggering of acute MI: l) Pharmacologic means of Prevention - that beta blockers, aspirin, angiotensin converting enzyme inhibitors and estrogen use decrease susceptibility to triggers; 2) Timing - that susceptibility does not increase in the morning but does in the winter, and that exogenous rather than endogenous daily rhythms determine onset; 3) Traditional chronic risk factors - that diabetes, hypertension, and smoking increase susceptibility and that regular exercise decreases susceptibility (to triggers other than exertion); 4) Gender - that women are less susceptible to triggering; and 5) Dietary factors - that chronic moderate alcohol use and anti- oxidants decrease susceptibility. To test the above hypotheses, 5,700 interviews are needed. By the completion of the Determinants Study in March 1993, over 2,000 interviews will be complete. Continuation in the Modifiers Study of our current 77 interviews per month will provide the required 3,700 additional interviews by December 1997. To maintain the study organization during the 8 month review of the Modifiers Study, we will support nurse interviewing with limited non-federal funds. The long-term goal of the proposed study is to identify more completely the mechanisms by which triggering occurs, and thereby facilitate identification of new means of prevention. Although most potential triggering activities are unavoidable, triggering of acute Ml could be prevented by using drugs or other interventions to sever the physiologic link between potential triggers and their catastrophic consequences.