Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction

项目摘要/摘要： 有心肌缺血体征和症状的女性通常接受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(在临床指示的冠状动脉造影术中定义为50%的心外膜狭窄) 错误地确信他们的症状是非心脏的。过去十年的证据表明，冠状动脉 微血管功能障碍(CMD)相关的缺血可能是此类病例的一种解释。已关联CMD 随着重大不良心血管事件(MACE)风险的增加，估计有300万女性 受CMD的影响。心脏正电子发射断层扫描(PET)成像可通过定量检测CMD 心肌血流储备(MFR)。然而，CMD的治疗策略开发得很差，有限 为临床医生治疗CMD提供信息的研究。这种治疗的不确定性是由于这样一个事实： CMD的基本病理生理机制尚不完全清楚。患有CMD的女性通常有 较高的心理社会负担和心绞痛通常是由心理压力引起的，这意味着 自主神经系统(ANS)障碍。我们的假设是，在CMD女性中，交感神经激活 在此期间，心理压力会导致冠状动脉微血管收缩。在本提案中，我们将测试 假设患有CMD的女性具有夸大的交感神经激活和异常的血管反应性 精神压力，这使他们即使在没有梗阻性CAD的情况下也容易出现不良后果。 三组绝经后妇女，年龄≥50岁将进行比较：(1)有症状的妇女无 梗阻性冠心病患者(通过PET衍生的MFR&lt；2.0)(n=50)；(2)有症状的女性梗阻性心脏病患者 冠心病(n=50)；(3)无症状对照(n=50)。两个对照组的年龄都将匹配到 CMD小组。我们将评估心脏交感神经活动(使用123I-间碘间苯基胍(MIBG)) 成像)和自主神经系统对急性精神压力的反应(目标1)。急性血管反应性 还将评估精神压力(目标2)。除了实验室引起的精神压力外，我们还建议 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 在使用可穿戴传感器和智能手机进行实时数据的一周家庭监控期间，不平衡 集合(目标3)。心绞痛住院和生活质量将在12个月的随访中进行评估， 和梅斯一起。实现这些目标将提供至关重要的缺失环节，即是否夸大 交感神经活动在CMD女性中占主导地位。这项工作的发现将为未来的干预提供信息 努力集中在ANS调制的效用上，以管理这一高危、研究不足的患者群体。

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.