Sex Differences in Myocardial Ischemia Triggered by Emotional Factors after MI

描述(申请人提供)：冠心病(CHD)是美国女性的主要死亡原因，每年有类似数量的女性和男性死于CHD。越来越多的证据支持女性和男性在冠心病的病理生理学、临床表现和预后方面的重要差异；然而，关于女性冠心病的独特特征，仍有许多需要了解。与同龄男性相比，年轻和中年女性在急性心肌梗死(MI)后的死亡率和并发症发生率更高。这些差异的原因尚不清楚；它们不能用传统的CHD风险因素、其他合并症或治疗方法来解释，尽管女性比男性冠状动脉粥样硬化更少，心脏功能得到更多保护，但仍会发生这些差异。三分之一至三分之二的冠心病患者患有由心理应激源引起的心肌缺血。这种缺血通常是无痛的，与冠状动脉疾病的严重程度无关；然而，它与不良后果有关。情绪因素，如抑郁和心理创伤，在女性冠心病患者中比男性更常见，可能使女性更容易受到应激诱导的缺血。例如，在60岁以下的MI女性中，抑郁症的比例高达40%。然而，情绪性脑缺血以前很少在女性身上进行研究。这项提案的总体目标是评估60岁以下的50名女性和50名男性在过去6个月内因急性心肌梗死而在埃默里附属医院住院的应激性脑缺血方面的差异。我们假设，由于情绪因素导致的心肌缺血在女性中比男性更常见，而运动性心肌缺血在女性中同样常见，甚至更不常见。本研究的目的是：(1)使用单光子发射断层扫描(SPECT)[Tc-99m]Sestamibi心肌灌注成像，比较女性和男性在休息、运动和情绪应激挑战时的心肌灌注。(2)探讨情绪应激引起的脑缺血性别差异的生物学机制，包括血流动力学(血压、心率)、神经生物学(皮质醇和自主神经系统)以及对应激刺激的炎症反应的差异。(3)探讨情绪应激(抑郁、创伤病史、社会经济环境)所致脑缺血性别差异的行为/心理社会解释因素。患有心肌梗塞的年轻女性代表了一个研究不足的患者群体，尽管她们的不良事件发生率比男性更高。对这一群体的调查将为预防女性冠心病提供关键信息。我们的研究可能会揭示一条独特的途径，可以解释MI结局中的性别差异。公共卫生相关性：冠心病是美国女性死亡的主要原因，然而，关于这种疾病在女性中的独特特征，仍有许多需要了解。青年和中年女性急性心肌梗死(MI)后的死亡率和并发症发生率更高，心理社会危险因素的负担也更高。这项研究将评估心梗后情绪触发的缺血在女性中是否比男性更常见，它是否与女性常见的心理社会风险因素相关，如抑郁和创伤史，以及是否与可能具有预后意义的生物变化有关，如血流动力学、神经生物学和对应激的炎症反应。

DESCRIPTION (provided by applicant): Coronary heart disease (CHD) is the major cause of death in American women, and every year a similar number of women and men die due to CHD. Growing evidence supports important differences in the pathophysiology, clinical presentation and prognosis of CHD between women and men; yet much remains to be learned about the unique characteristics of CHD in women. Young and middle-aged women have higher mortality and complication rates after an acute myocardial infarction (MI) compared with men of similar age. Reasons for these differences are unknown; they are not explained by traditional CHD risk factors, other comorbidity or treatments, and occur despite the fact that women have less coronary atherosclerosis and more preserved ventricular function than men. One third to two thirds of patients with CHD have myocardial ischemia that is induced by psychological stressors. Such ischemia is often painless and unrelated to severity of coronary artery disease; nonetheless it is associated with adverse outcomes. Emotional factors such as depression and psychological trauma are more common in women with CHD than in men and may predispose women to stress-induced ischemia. Depression, for example, is present in up to 40% of women with MI younger than 60 years. However, emotionally-triggered ischemia has hardly been studied in women before. The overall objective of this proposal is to evaluate differences in stress-induced ischemia between 50 women and 50 men younger than 60 years who were hospitalized for acute MI in the previous 6 months in Emory- affiliated hospitals. We hypothesize that myocardial ischemia due to emotional factors is more common in women than in men, while exercise-induced ischemia is as common, or even less common, in women. The aims of this study are: (1) Using single photon emission tomography (SPECT) [Tc-99m] sestamibi myocardial perfusion imaging, to compare myocardial perfusion during rest, during exercise, and during an emotionally stressful challenge in women and men. (2) To investigate biological mechanisms for the sex differences in ischemia induced by emotional stress, including differences in hemodynamic (blood pressure, heart rate), neurobiological (cortisol and autonomic nervous system) and inflammatory responses to the stressful challenge. (3) To investigate behavioral/psychosocial explanatory factors for the sex differences in ischemia induced by emotional stress (depression, history of trauma, and socio-economic environment). Younger women with MI represent an understudied patient group despite their higher rate of adverse events compared with men. Investigation of this group will provide critical information for the prevention of CHD in women. Our study may uncover a unique pathway which may explain sex differences in the outcome of MI. PUBLIC HEALTH RELEVANCE: Coronary heart disease is the major cause of death in American women and yet, much remains to be learned about the unique characteristics of this disease in women. Young and middle-aged women have higher mortality and complication rates after an acute myocardial infarction (MI) and higher burden of psychosocial risk factors. This study will evaluate whether emotionally triggered ischemia is more common in women than in men after MI, whether it is correlated with psychosocial risk factors that are common in women, such as depression and history of trauma, and whether it is associated with biological changes that may have prognostic significance, such as hemodynamic, neurobiological and inflammatory responses to stress.