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）是世界范围内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。急性心肌梗死妇女的预后比男性差，急性心肌梗死后的病死率更高，发病率和死亡率也更高。有限的侵入性和尸检研究已经确定了AMI表现时冠状动脉粥样硬化斑块特征的性别差异。迄今为止，还没有研究检验(a) AMI发生前个体动脉粥样硬化斑块特征（APC）的性别差异，以及(b) APC评估是否可以改善稳定CAD但未来有可能发生AMI的女性和男性的分层。冠状动脉CT血管造影（CT）是一种非侵入性检查，可诊断冠状动脉狭窄，男女诊断准确率高，并可评估动脉粥样硬化斑块和冠状动脉壁特征。我们最近开展了一项前瞻性多中心国际CONFIRM观察队列研究，对32,308例接受CT检查的患者进行了仔细随访，包括全面的CAD危险因素、图像发现和CAD事件确定。我们建议利用这一丰富的资源来阐明冠状动脉狭窄造影之外冠状动脉斑块特征的性别特异性预后意义，以无创识别与未来AMI相关的冠状动脉病变。本提案的总体假设是，CT量化的APCs将增强对导致未来AMI的冠状动脉斑块的性别特异性识别。为了检验这一点，我们在CAD、CT、女性健康、结果研究和流行病学方面组建了一支无与伦比的领先研究团队。我们描述了一项研究方案，该方案是我们之前工作的逻辑和自然延伸，具有3个具体目标：目的1：确定冠状动脉斑块的动脉粥样硬化特征，这些特征随后与未来的AMI有关。目的2：比较女性和男性冠状动脉斑块的性别差异。目的3：确定预测AMI的冠状动脉粥样硬化斑块特征的性别特异性风险。如果成功，这项工作将为一种新的诊断和潜在的治疗范式提供基本原理，这种范式不仅可以精确识别未来AMI风险的女性和男性，还可以识别与性别相关的冠状动脉病变。

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.