Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction

项目概要/摘要： 有心肌缺血症状和体征的妇女通常进行冠状动脉造影以诊断 阻塞性心外膜冠状动脉疾病（CAD）;然而，大约50%的人被发现没有 阻塞性CAD（定义为临床指征冠状动脉造影显示心外膜狭窄<50%）， 错误地保证他们的症状不是心脏病。过去十年的证据表明， 微血管功能障碍（CMD）相关的局部缺血可能是这种情况的一种解释。CMD与 主要不良心血管事件（MACE）的风险增加，估计有300万妇女 受到CMD的影响。心脏正电子发射断层扫描（PET）成像可以通过定量检测CMD 心肌血流储备（MFR）。然而，治疗策略在CMD中发展不足， 研究，以告知临床医生对CMD的治疗。这种治疗上的不确定性是由于 CMD的潜在病理生理机制还不完全清楚。患有CMD的女性通常 高心理社会负担和心绞痛往往是由心理压力，这意味着 自主神经系统（ANS）功能障碍。我们的假设是，在CMD女性中，交感神经激活 导致冠状动脉微血管收缩。在本提案中，我们将测试 CMD女性交感神经激活过度和血管反应性异常假说 精神压力，这使他们倾向于不利的结果，即使在没有阻塞性CAD。 将比较三组年龄≥50岁的绝经后妇女：（1）无症状的妇女， 患有CMD的阻塞性CAD（PET衍生MFR < 2.0）（n=50）;（2）患有阻塞性CAD的症状性女性 CAD（n=50）;和（3）无症状参考对照（n=50）。两个对照组将年龄匹配， CMD集团。我们将评估心脏交感神经活动（使用123 I-间碘苄胍（MIBG）） 成像）和自主神经系统对急性精神应激的反应性（目的1）。血管对急性 此外，亦会评估精神压力（目标2）。除了实验室引起的精神压力，我们建议 检查慢性和日常生活压力，负面情绪，心绞痛症状和自主神经的重要作用 使用可穿戴传感器和智能手机进行为期一周的家庭监测以获取实时数据 收集（目标3）。心绞痛住院治疗和生活质量将在12个月随访时进行评估，沿着期间 关于MACE实现这些目标将提供至关重要的缺失环节， 交感神经活动在患有CMD的女性中占主导地位。这项工作的结果将为未来的干预提供信息 努力集中在ANS调节的效用上，用于管理这个高风险的、未充分研究的患者组。

Project Summary/Abstract: Women with signs and symptoms of myocardial ischemia usually undergo coronary angiography to diagnose obstructive epicardial coronary artery disease (CAD); however, approximately 50% are found to have no obstructive CAD (defined as <50% epicardial stenosis on clinically indicated coronary angiography) and are falsely reassured that their symptoms are non-cardiac. Evidence over the past decade indicates that coronary microvascular dysfunction (CMD)-related ischemia may be an explanation in such cases. CMD is associated with increased risk of major adverse cardiovascular events (MACE) and an estimated 3 million women are impacted by CMD. Cardiac positron emission tomography (PET) imaging can detect CMD by quantifying myocardial flow reserve (MFR). However, therapeutic strategies are poorly developed in CMD, with limited studies to inform clinicians on treatment of CMD. This therapeutic uncertainty results from the fact that the underling pathophysiologic mechanisms of CMD are incompletely understood. Women with CMD typically have a high psychosocial burden and their angina is often induced by psychological stress, which implicates autonomic nervous system (ANS) dysfunction. Our hypothesis is that in CMD women, sympathetic activation during psychological stress drives coronary microvascular constriction. In this proposal we will test the hypothesis that women with CMD have exaggerated sympathetic activation and abnormal vasoreactivity to mental stress, which predisposes them to adverse outcomes even in the absence of obstructive CAD. Three groups of post-menopausal women, ages ≥50 years will be compared: (1) symptomatic women with no obstructive CAD who have CMD (by PET-derived MFR < 2.0) (n=50); (2) symptomatic women with obstructive CAD (n=50); and (3) asymptomatic reference controls (n=50). Both comparison groups will be age-matched to the CMD group. We will assess cardiac sympathetic activity (using123I-meta-iodobenzylguanidine (MIBG) imaging) and autonomic nervous system reactivity to acute mental stress (Aim 1). Vascular reactivity to acute mental stress will also be assessed (Aim 2). In addition to laboratory-induced mental stress, we propose to examine the important role of chronic and daily life stress, negative emotions, anginal symptoms and autonomic imbalance during one week of home monitoring using wearable sensors and a smartphone for real-time data collection (Aim 3). Anginal hospitalization and quality of life will be assessed at 12 months of follow-up, along with MACE. Accomplishing these aims will provide the critically important missing link of whether exaggerated sympathetic activity is predominant in women with CMD. Findings from this work will inform future intervention efforts centered on the utility of ANS modulation for the management of this high-risk, understudied patient group.