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

摘要 心血管疾病是妇女死亡的主要原因。在有症状的 在接受冠状动脉造影的女性中，40-65%没有阻塞性冠状动脉疾病 （CAD）。考虑到低风险，他们往往没有接受特定的治疗。然而，现在的证据表明， 这类女性发生主要不良心脏事件的风险高于预期。的 WARRIOR试验是一项多中心、前瞻性、随机、盲态结局评价， 阿司匹林、他汀类药物、血管紧张素转换酶抑制剂强化药物治疗（IMT） ACEI和/或血管紧张素受体阻滞剂（ARB）与常规治疗（UC）在4，422名女性中的比较 缺血症状和非梗阻性CAD。WARRIOR的假设是IMT将 减少主要的不良心脏事件，包括心绞痛和住院。我们假设 IMT的有益作用可能是由于斑块成分和血流储备的变化 与内皮和微血管功能障碍有关，而不是狭窄减少 严重性。冠状动脉计算机断层扫描（CT）血管造影（CTA）可识别高危斑块 与内皮功能障碍和心肌缺血相关的特征。最近的研究 显示斑块炎症抑制冠状动脉周围脂肪细胞成熟， 组织（PCAT），并反过来增加PCAT的密度。因此，定量CTA可能 允许对斑块负荷、冠状动脉流量和 斑块炎症我们已经开发了经过验证的软件，用于定量表征 使用CTA测量斑块和PCAT密度。在这项辅助子研究中，我们将招募400名患者， WARRIOR试验，每个治疗组200例患者（IMT vs UC）。从这个 队列，每个治疗组150例患者，最符合WARRIOR方案，将接受 3年结束时的CTA;量化斑块和PCAT特征的变化。我们 提出3个目的：（1）比较冠状动脉斑块特征的变化及其 在接受IMT与UC治疗的WARRIOR女性中使用CTA的血流动力学意义;（2） 比较WARRIOR女性PCAT中斑块炎症相关特征的变化 他汀类药物联合血管紧张素转换酶抑制剂（ACEI）治疗IMT 和/或血管紧张素受体阻滞剂（ARB）药物与UC;（3）将斑块负荷与 斑块组成、CT血流储备和PCAT密度变化与心绞痛评分（西雅图心绞痛 调查问卷[SAQ]）中IMT和UC随机WARRIOR女性的变化。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 缺血性症状和非梗阻性CAD女性患者的临床改善。

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.