Gender-Specific Coronary Plaque Characteristics and Risk of Myocardial Infarction

性别特异性冠状动脉斑块特征和心肌梗塞的风险

• 批准号: 8346584
• 负责人: James K Min
• 金额: $ 78.4万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-20 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8346584
• 关键词: Acute myocardial infarction; Agreement; Anatomy; Angiography; Arterial Fatty Streak; Autopsy; Awareness; Calcified; Case Fatality Rates; Cessation of life; Characteristics; Clinical; Cohort Studies; Coronary; Coronary Arteriosclerosis; Coronary Stenosis; Coronary artery; Detection; Diagnosis; Diagnostic; Epidemiology; Evaluation; Event; Exclusion; Exhibits; Frequencies; Future; Gender; Image; Individual; International; Investigation; Lesion; Measures; Methods; Morbidity - disease rate; Morphology; Myocardial Infarction; Nature; Necrosis; Nodule; Outcomes Research; Pathogenesis; Pathologic; Patients; Performance; Protocols documentation; Reporting; Research Personnel; Resources; Risk; Risk Factors; Rupture; Severities; Sex Characteristics; Site; Stenosis; Stratification; Stress Tests; Symptoms; Testing; Therapeutic; Time; Ultrasonography; Woman; Women' s Health; Work; X-Ray Computed Tomography; base; clinical application; coronary computed tomography angiography; diagnostic accuracy; disorder risk; experience; heart imaging; high risk; improved; men; mortality; novel diagnostics; outcome forecast; prognostic; prospective

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.

描述（由申请人提供）：冠状动脉疾病（CAD）是全世界发病和死亡的主要原因，超过一半的急性心肌梗死（AMI）患者没有先兆症状。女性 AMI 的预后比男性差，病死率更高，AMI 后时期的发病率和死亡率更高。有限的侵入性和尸检研究已经确定了 AMI 出现时冠状动脉粥样硬化斑块特征的性别差异。迄今为止，尚无研究检验 (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 评估是否可以改善对患有稳定 CAD 但面临未来未预见的 AMI 风险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，可对女性和男性的冠状动脉狭窄进行高诊断准确度诊断，并可评估动脉粥样硬化斑块和冠状动脉壁特征。我们最近开展了前瞻性多中心国际 CONFIRM 观察性队列研究，对 32,308 名接受 CT 治疗的患者进行了仔细随访，包括全面的 CAD 风险因素、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斑块特征在血管造影冠状动脉狭窄之外的性别特异性预后意义，以非侵入性地识别未来 AMI 中涉及的冠状动脉病变。本提案的总体假设是，通过 CT 量化的 APC 将增强对将导致未来 AMI 的冠状动脉斑块的性别特异性识别。为了研究这一点，我们组建了一支由 CAD、CT、女性健康、结果研究和流行病学领域的领先研究人员组成的无与伦比的团队。我们描述了一项研究方案，它是我们之前工作的逻辑和自然延伸，具有 3 个具体目标： 目标 1：确定冠状动脉斑块的动脉粥样硬化特征，这些特征随后将与未来的 AMI 相关。目标 2：比较随后将经历 AMI 的女性与男性冠状动脉斑块的性别差异。目标 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，该提案中的工作将为新型诊断和潜在治疗范例提供理论基础，该范例不仅可以精确识别未来有 AMI 风险的女性和男性，还可以识别出导致 AMI 的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，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。心脏计算机断层扫描（CT）现在可以对冠状动脉斑块特征进行非侵入性评估。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，这可能会重新定义疑似 CAD 女性和男性的诊断方法。