Gender-Specific Coronary Plaque Characteristics and Risk of Myocardial Infarction

描述(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。女性急性心肌梗死患者的预后比男性更差，病死率更高，在急性心肌梗死后阶段的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急性心肌梗死患者发病时冠状动脉粥样硬化斑块特征的性别差异。到目前为止，还没有研究检验(A)在急性心肌梗死发生前个体的动脉粥样硬化斑块特征(APC)的性别差异，以及(B)APC评估是否可以改善对患有稳定的CAD但有未来无症状急性心肌梗死风险的女性和男性的分层。冠状动脉CT血管成像(CT)是一种非侵入性检查，可以对女性和男性的冠状动脉狭窄进行高准确率的诊断，以及评估动脉粥样硬化斑块和冠状动脉壁特征。我们最近开展了前瞻性多中心国际确证观察队列研究，对32,308名接受CT检查的患者进行了仔细跟踪，包括综合的CAD危险因素、影像发现和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造影狭窄以外的冠状动脉斑块特征对于非侵入性识别未来急性心肌梗死所涉及的冠状动脉病变的特定性别的预后意义。目前建议的总体假设是，CT量化的APC将加强对导致未来急性心肌梗死的冠状动脉斑块的性别特异性识别。为了检验这一点，我们组建了一支由CAD、CT、妇女健康、结果研究和流行病学方面的领先研究人员组成的无与伦比的团队。我们描述了一个研究方案，它是我们先前工作的合理和自然的扩展，有三个具体的目标：目标1：识别冠状动脉斑块的动脉粥样硬化特征，这些斑块随后将被牵连到未来的急性心肌梗死。目的2：比较女性和男性在冠状动脉斑块中的性别差异，这些患者随后会经历未来的急性心肌梗死。目的3：确定预测急性心肌梗死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，这项建议中的工作将为一种新的诊断和潜在的治疗范例提供理论基础，该范例不仅准确地识别出未来有急性心肌梗死风险的女性和男性，而且还能识别与病因有关的特定性别的冠状动脉病变。 公共卫生相关性：对于有心脏病发作风险的女性和男性，对冠状动脉疾病(CAD)患者的研究传统上侧重于阻塞的严重程度，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)现在可以无创地评估冠状动脉斑块的特征。这项研究将按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，这可能会重新定义对疑似冠心病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.