Gender-Specific Coronary Plaque Characteristics and Risk of Myocardial Infarction

描述（由申请人提供）：冠状动脉疾病（CAD）是全球发病率和死亡率的主要基础，超过一半的急性心肌梗死（AMI）患者没有先兆症状。女性AMI患者的预后比男性差，AMI后的病死率和发病率及死亡率更高。有限的侵入性和尸检研究已经确定了性别特异性差异的冠状动脉粥样硬化斑块的特点，在提出的AMI。到目前为止，还没有研究检查（a）AMI发生前个体动脉粥样硬化斑块特征（APC）的性别差异和（B）APC评估是否可以改善目前患有稳定CAD但未来有发生意外AMI风险的女性和男性的分层。冠状动脉CT血管造影术（CT）是一种无创性检查，可诊断女性和男性冠状动脉狭窄，诊断准确率高，并可评价动脉粥样硬化斑块和冠状动脉壁特征。我们最近开发了一项前瞻性多中心国际CONFIRM观察性队列研究，该研究纳入了32，308例接受CT检查的患者，这些患者具有全面的CAD风险因素、影像学发现和CAD事件确定。我们建议利用这一丰富的资源，以阐明性别特异性的预后意义的冠状动脉斑块的特点，超越血管造影冠状动脉狭窄的非侵入性识别冠状动脉病变，将涉及在未来的AMI。本提案的总体假设是，通过CT定量的APC将增强性别特异性识别将导致未来AMI的冠状动脉斑块。为了研究这一点，我们组建了一支无与伦比的CAD，CT，女性健康，结果研究和流行病学领先研究人员团队。我们描述了一个研究方案，这是一个逻辑和自然的延伸，我们以前的工作有3个具体目标：目的1：确定冠状动脉粥样硬化斑块的特征，随后将牵连在未来的AMI。目的2：比较女性与男性在冠状动脉斑块中的性别特异性差异，这些患者随后将经历未来的AMI。目的3：确定性别特异性危险的冠状动脉粥样硬化斑块的特点，预示着急性心肌梗死。如果成功的话，这项提案中的工作将为一种新的诊断和潜在的治疗模式提供理论基础，不仅可以精确识别未来AMI风险的女性和男性，而且还可以识别性别特异性冠状动脉病变。 公共卫生相关性：对于有心脏病发作风险的女性和男性，冠状动脉疾病（CAD）患者的研究传统上集中在阻塞的严重程度上，而不是冠状动脉斑块特征或心脏动脉阻塞的构成。心脏的计算机断层扫描（CT）现在允许对冠状动脉斑块特征进行非侵入性评估。这项研究将根据性别评估冠状动脉斑块的具体构成，并确定其与未来心脏病发作风险的关系，这可能会重新定义疑似CAD的女性和男性的诊断方法。

DESCRIPTION (provided by applicant): Coronary artery disease (CAD) is the principal basis of morbidity and mortality worldwide, and more than half of individuals experiencing acute myocardial infarction (AMI) have no premonitory symptoms. The prognosis for women with AMI is worse than for men, with higher case fatality rates and greater morbidity and mortality in the post-AMI period. Limited invasive and autopsy studies have identified gender-specific differences in coronary atherosclerotic plaque features at the time of presentation of AMI. To date, no study has examined (a) gender differences in atherosclerotic plaque characteristics (APCs) for individuals before AMI occurrence and (b) whether APC assessment can improve stratification of women and men who present with stable CAD but are at risk for future unheralded AMI. Coronary CT angiography (CT) is a non-invasive test that permits diagnosis of coronary stenosis with high diagnostic accuracy in women and men, as well as evaluation of atherosclerotic plaque and coronary arterial wall features. We have recently developed the prospective multicenter international CONFIRM observational cohort study of 32,308 carefully followed patients undergoing CT with comprehensive CAD risk factor, image finding, and CAD event ascertainment. We propose to use this rich resource to elucidate the gender-specific prognostic significance of coronary artery plaque characteristics beyond angiographic coronary stenosis for the non-invasive identification of coronary lesions that will be implicated in future AMI. The OVERALL HYPOTHESIS of the present proposal is that APCs quantified by CT will enhance gender- specific identification of coronary plaques that will cause future AMI. To examine this, we have assembled an unparalleled team of leading researchers in CAD, CT, women's health, outcomes research, and epidemiology. We describe a study protocol that is a logical and natural extension of our prior work with 3 specific aims: AIM 1: To identify the atherosclerotic features of coronary plaques that will be subsequently implicated in future AMI. AIM 2: To compare gender-specific differences in coronary plaques for women versus men who will subsequently experience future AMI. AIM 3: To determine the gender-specific risk of coronary atherosclerotic plaque characteristics that prognosticates AMI. If successful, the work in this proposal will provide the rationale for a novel diagnostic and potentially therapeutic paradigm that not only precisely identifies women and men who are at risk for future AMI, but also the gender-specific coronary lesions implicated as the cause. PUBLIC HEALTH RELEVANCE: For women and men who are at risk of developing heart attacks, the study of patients with coronary artery disease (CAD) has traditionally been focused on severity of blockages, rather than coronary plaque characteristics, or the makeup of blockages in heart arteries. Computed tomography (CT) scans of the heart now allow for non-invasive evaluation of coronary plaque characteristics. This study will evaluate the specific makeup of coronary plaque by gender and determine its relationship to risk of future heart attacks, which may redefine the diagnostic approach to women and men with suspected CAD.