Effect of Intensive Medical Treatment on Quantified Coronary Artery Plaque Components with Serial Coronary CTA in Women with Non-Obstructive CAD

强化治疗对非阻塞性 CAD 女性连续冠状动脉 CTA 量化冠状动脉斑块成分的影响

• 批准号: 10247453
• 负责人: Damini Dey
• 金额: $ 39.25万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247453
• 关键词: Adipocytes; Adipose tissue; Age; Ancillary Study; Angiography; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Arterial Fatty Streak; Arteries; Aspirin; Blinded; Cardiac; Cardiovascular Diseases; Characteristics; Chest Pain; Cholesterol; Clinical; Computer software; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary artery; Diagnosis; Endothelium; Evaluation; Event; Functional disorder; Heart Diseases; Hospitalization; Inflammation; Inflammatory; Ischemia; LDL Cholesterol Lipoproteins; Measures; Medical; Microvascular Dysfunction; Myocardial Ischemia; Necrosis; Outcome; Patients; Pharmaceutical Preparations; Protocols documentation; Questionnaires; Randomized; Risk; Scanning; Severities; Stenosis; Symptoms; Woman; Work; X-Ray Computed Tomography; atherogenesis; attenuation; cohort; coronary computed tomography angiography; coronary plaque; density; endothelial dysfunction; experience; hemodynamics; high risk; imaging study; improved; indexing; insight; men; mortality; non-invasive imaging; pain symptom; prospective; recruit; response; sex; software development; tool; treatment as usual; treatment group

ABSTRACT Cardiovascular disease is the leading cause of mortality among women. Among symptomatic women presenting to coronary angiography, 40-65% have no obstructive coronary artery disease (CAD). Considered low risk, they often receive no specific therapy. Yet, evidence now documents that such women have higher than expected risk for major adverse cardiac events. The WARRIOR trial is a multicenter, prospective, randomized, blinded outcome evaluation evaluating intensive medical therapy (IMT) with aspirin, statin, angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) vs. usual care (UC) in 4,422 women with ischemic symptoms and non- obstructive CAD. The hypothesis of WARRIOR is that IMT will reduce major adverse cardiac events including angina and hospitalization. We hypothesize that the beneficial effects of IMT may be due to changes in plaque composition and flow reserve related to endothelial and microvascular dysfunction rather than from reduction in stenosis severity. Coronary computed tomographic (CT) angiography (CTA) can identify high-risk plaque features associated with endothelial dysfunction and myocardial ischemia. Recent studies have shown that plaque inflammation inhibits adipocyte maturation in pericoronary artery adipose tissue (PCAT) and in turn increases the density of PCAT. Thus, quantitative CTA can potentially allow a comprehensive noninvasive evaluation of changes in plaque burden, coronary flow and plaque inflammation. We have developed validated software for quantitative characterization of plaque and PCAT density using CTA. In this ancillary substudy, we will recruit 400 patients from the WARRIOR trial with 200 patients from each of the treatment groups (IMT vs UC). From this cohort, 150 patients per treatment group, most compliant with WARRIOR protocol will undergo a CTA at the end of 3 years; with changes in plaque and PCAT characteristics quantified. We propose 3 aims: (1) To compare changes in coronary plaque characteristics and their hemodynamic significance using CTA in WARRIOR women treated with IMT vs UC; (2) To compare changes in plaque inflammation-related characteristics in PCAT in WARRIOR women treated with IMT with statin in combination with angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) medications vs UC; (3) To relate plaque burden and plaque composition, CT flow reserve, and PCAT density changes to angina score (Seattle Angina Questionnaire [SAQ]) changes in IMT and UC-randomized WARRIOR women. Our study will be the first to quantify the impact of IMT on plaque composition and inflammation and its relation to clinical improvement in women with ischemic symptoms and nonobstructive CAD.

抽象的 心血管疾病是女性死亡的主要原因。有症状 出现在冠状动脉造影的妇女，有40-65％的妇女没有阻塞性冠状动脉疾病 （CAD）。被认为是低风险，他们通常没有得到特定的治疗。但是，证据现在文件 这样的妇女对重大不良心脏事件的风险高于预期的风险。这 战士试验是一个多中心，前瞻性，随机，盲目的结果评估评估 阿司匹林，他汀类药物，血管紧张素转化酶抑制剂的强化医疗疗法（IMT） （ACEI）和/或血管紧张素受体阻滞剂（ARB）与4,422名患有女性的平常护理（UC） 缺血性症状和非阻塞性CAD。战士的假设是IMT将 减少重大不良心脏事件，包括心绞痛和住院。我们假设这一点 IMT的有益效果可能是由于斑块组成和流量储备的变化所致 与内皮和微血管功能障碍有关，而不是狭窄的减少 严重程度。冠状动脉层析成像（CT）血管造影（CTA）可以识别高风险牌匾 与内皮功能障碍和心肌缺血有关的特征。最近的研究 表明牙菌斑炎症抑制周心动脉脂肪中的脂肪细胞的成熟 组织（PCAT）和进而增加PCAT的密度。因此，定量CTA可以潜在地 允许对斑块负担的变化，冠状动脉流动和 斑块炎症。我们已经开发了经过验证的软件来定量表征 使用CTA的斑块和PCAT密度。在这个辅助物质中，我们将从中招募400名患者 战士试验，来自每个治疗组的200名患者（IMT与UC）。由此 队列，每个治疗组150名患者，最符合战士方案的患者将接受 CTA在3年结束时；随着牙菌斑和PCAT特征的变化进行了量化。我们 提出3个目标：（1）比较冠状斑块特征及其的变化 使用IMT与UC治疗的战士妇女中CTA使用CTA的血液动力学意义； （2）至 比较战士女性PCAT斑块炎症特征的变化 用他汀类药物与血管紧张素转化酶抑制剂（ACEI）一起处理IMT（ACEI） 和/或血管紧张素受体阻滞剂（ARB）药物与UC； （3）关联牌匾负担和 斑块组成，CT流量储备和PCAT密度变为心绞痛（西雅图心绞痛） 问卷[SAQ]）IMT和UC随机战士妇女的变化。我们的研究将是 第一个量化IMT对斑块组成和炎症的影响及其与之的关系 有缺血性症状和非焦化性CAD的女性的临床改善。