MODIFIERS OF MYOCARDIAL INFARCTION ONSET

心肌梗死发作的调节因素

• 批准号: 2028400
• 负责人: JAMES E MULLER
• 金额: $ 49.22万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2028400
• 关键词: acute disease /disorder; aspirin; beta antiadrenergic agent; cardiovascular disorder epidemiology; cardiovascular disorder prevention; case history; chemoprevention; circadian rhythms; data collection methodology /evaluation; diet; disease /disorder proneness /risk; exercise; gender difference; human subject; interview; myocardial infarction; physiologic stressor; psychological stressor; questionnaires; smoking; stress

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.

这是一项修订后的竞争性续展申请，用于进行研究 题为“心肌梗死发作的修饰因素”（修饰因素研究） 阐明急性心肌梗死（ML）的病理生理学 发病。我们将利用方法论技术，50 家医院 国家研究小组以及由 NHLBl 资助完成的研究结果 心肌梗死发病的决定因素研究（决定因素研究）。 修正研究将确定增加或减少的因素 患者对急性 Ml 诱因的易感性 先前已确定。 决定因素研究开始于 1989 年，在广泛传播后不久 接受 Ml 发生的昼夜节律变化。该研究是 开始利用最先进的流行病学技术 确定日常活动在触发 Ml 中的作用。这 研究人员创建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 页的访谈表格，建立了 建立了由经过培训的采访员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该领域的核心 发展触发急性疾病发作的研究领域。 决定因素研究实现了四个具体目标。它 证明了觉醒/活动，而不是绝对时间 一天，负责早上触发，即劳累、愤怒， 性活动是 Ml 的触发因素，相对风险为 6、3 和 2 分别表示，β-封锁可防止通过以下方式触发 觉醒/活动，久坐的生活方式显着增加 剧烈运动引发 Ml 的相对风险。 拟议的修饰符研究将回答以下提出的主要问题 决定因素研究的结果。它将检验假设 关于 5 组潜在的调节因素 触发急性心肌梗死的易感性： 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会降低对触发因素的敏感性； 2) 时间——敏感性在早上不会增加​​，但 在冬天，每天都是外源性的而不是内源性的 节律决定发作； 3) 传统的慢性危险因素——即 糖尿病、高血压和吸烟会增加易感性 定期锻炼可以降低对其他触发因素的敏感性 用力）; 4) 性别——女性不易触发； 5) 饮食因素——长期适度饮酒和抗- 氧化剂降低敏感性。 为了检验上述假设，需要进行 5,700 次访谈。由 1993 年 3 月完成决定因素研究，超过 2,000 面试将会完成。 修饰语研究的继续 我们目前每月 77 次采访将提供所需的 3,700 1997 年 12 月之前进行额外访谈。为了维持研究 在为期 8 个月的修改研究审查期间，我们将 使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。虽然最有潜力 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 潜在触发因素与其灾难性后果之间的生理联系 结果。