MODIFIERS OF MYOCARDIAL INFARCTION ONSET

这是一份修订后的竞争续订申请，用于进行研究 题为心肌梗死发病的修饰物(修饰物研究) 阐明急性心肌梗死的病理生理机制(毫升) 开始了。我们将利用方法论技术，50家医院 国家研究小组，以及完成的NHLB1资助的结果 心肌梗塞发病的决定因素研究(决定因素研究)。 修饰剂研究将确定增加或减少 患者对急性多发性硬化症的易感性 之前确认过的。 决定因素研究始于1989年，在广泛传播之后不久 对ML发生的昼夜节律变化的接受程度。这项研究是 发起利用最先进的流行病学技术 确定日常活动在ML的触发中的作用。这个 研究人员创造了一种新的流行病学技术(病例交叉 方法)，开发并测试了一份24页的面试表，建立了 建立了拥有训练有素的面试者的大型医院研究小组 采取质量控制措施，招收2000多名考生。这 广泛的活动使《决定者》研究成为 发展中的急性疾病发病触发研究领域。 决定因素研究实现了它的四个具体目标。它 证明了觉醒/活动，而不是绝对时间 白天，是早晨引发的，那沉重的劳累，愤怒， 和性行为是ML的触发因素，其相对风险为6、3和 2分别，这种β-封锁阻止了通过 觉醒/活动，久坐的生活方式显著增加 因用力过大而触发ML的相对风险。 拟议的修饰语研究将回答以下主要问题 决定因素研究的结果。它将检验假设 关于5组因素是潜在的修饰物 对急性心肌梗塞的易感性：L)药理学手段 预防-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诱因的敏感性； 2)时机--上午的敏感度不会增加，而是 在冬天是这样的，每天都是外源的，而不是内源的 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，而且 有规律的锻炼可降低易感性(对其他诱因 体力消耗)；4)性别--女性不太容易被触发； 5)饮食因素--长期适量饮酒和不饮酒 氧化剂会降低敏感性。 为了验证上述假设，本研究需要进行5700次访谈。由 决定因素研究于1993年3月完成，超过2,000人 采访将会结束。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人 在1997年12月之前进行更多面谈。来维持这项研究 组织在8个月的改良剂研究审查期间，我们将 用有限的非联邦资金支持护士面谈。 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。尽管最具潜力的 触发活动是不可避免的，急性ML的触发可能是 通过使用药物或其他干预措施来切断 潜在诱因及其灾难性之间的生理联系 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.