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

摘要 心血管疾病是女性死亡的主要原因。有症状的人中 接受冠状动脉造影术的女性中，40%-65%没有阻塞性冠状动脉疾病 (CAD)。由于被认为风险较低，他们通常不会接受特定的治疗。然而，现在有证据表明 这些妇女发生重大不良心脏事件的风险高于预期。这个 勇士试验是一项多中心、前瞻性、随机、盲法的结果评估 阿司匹林、他汀、血管紧张素转换酶抑制剂强化药物治疗(IMT) 接受血管紧张素转换酶抑制剂(ACEI)和/或血管紧张素受体阻滞剂(ARB)与常规护理(UC)治疗的4422名女性 缺血症状和非梗阻性冠心病。武士的假设是IMT将 减少包括心绞痛和住院在内的主要不良心脏事件。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改变。 与血管内皮细胞和微血管功能障碍有关，而不是与狭窄的减少有关 严肃性。冠状动脉CT血管造影术(CTA)可以识别高危斑块 与内皮功能障碍和心肌缺血相关的特征。最近的研究表明 斑块炎症抑制冠状动脉周围脂肪细胞成熟 组织(PCAT)，进而增加PCAT的密度。因此，定量的CTA可以潜在地 允许全面无创性评估斑块负荷、冠状动脉流量和 斑块发炎。我们已经开发了经过验证的软件，用于定量描述 CTA检测斑块和PCAT密度。在这项辅助性的子研究中，我们将从 WAROR试验，每个治疗组200名患者(IMT与UC)。由此 队列，每个治疗组150名患者，最符合勇士方案的患者将接受 3年后进行CTA检查，并量化斑块和PCAT特征的变化。我们 提出3个目标：(1)比较冠状动脉斑块特征的变化及其与冠状动脉病变的关系。 CTA对接受IMT和UC治疗的战士女性的血流动力学意义；(2) 比较战士女性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比较；(3)与斑块负荷和 斑块成分、CT血流储备和PCAT密度改变为心绞痛评分(西雅图心绞痛 调查问卷[SAQ])IMT和UC-随机分配的战士女性的变化。我们的研究将是 首次量化IMT对斑块成分和炎症的影响及其与 有缺血症状和非梗阻性冠心病的女性的临床改善。

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.