Mental Stress and Myocardial Ischemia after MI: Sex Differences and Mechanisms

描述（由申请人提供）： 急性心肌梗死（MI）是美国女性死亡的主要原因，但尽管最近的科学进步，目前尚不清楚其病理生理学是否在女性和男性之间存在差异。与同龄男性相比，年轻和中年（但不是老年）女性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;它们不能用传统的危险因素、合并症或治疗来解释，尽管女性的冠状动脉粥样硬化比男性少。这些发现仍然是女性缺血性心脏病流行病学中一个未解决的问题。妇女在心理社会风险因素方面的负担更大。例如，抑郁症在年轻（<60岁）MI女性中的发生率是其他人群的2倍，影响了高达40%的这一人群。因此，我们假设心理压力是年轻女性心肌梗死的主要危险因素，并可能解释心肌梗死病理生理学和预后的性别差异。在大约一半的缺血性心脏病患者中，心肌缺血可以由心理挑战引起;这种“心理应激缺血”为研究心理应激对心脏功能的影响提供了一个有用的模型。在这个项目中，我们将评估MI年轻幸存者精神应激缺血的患病率、机制和后果的性别差异。我们将比较150名女性和150名男性，年龄<60岁，在过去6个月内因MI住院。我们还将比较MI患者与60名女性和60名男性社区对照无MI。我们将检验这一假设，即在年轻的MI受试者中，精神应激缺血是女性比男性更强的危险因素，这是由于MI女性相对于MI男性和无MI女性对应激的生理和行为反应增强。本研究的目的是：（1）应用单光子发射断层显像（SPECT）[Tc-99 m]心肌灌注显像，比较60岁以下男性和女性在过去6个月内因确诊的心肌梗死住院患者在静息、精神应激和运动应激时的心肌灌注。(2)比较急性血管和炎症反应的压力之间的年轻女性和男性心肌梗死，年轻女性和男性心肌梗死和他们各自的社区控制。我们将研究休息和精神压力之间的变化，外周血管功能，全身炎症和免疫功能的措施，其次，神经内分泌和行为措施的变化。(3)比较年轻女性和男性MI患者的长期（6个月）血管和炎症结局。我们的建议将填补一个重大空白。年轻女性心肌梗死患者仍然是一个未充分研究的群体，尽管与男性相比，她们的不良事件发生率更高，并且可能特别容易受到心理压力的影响。对该组的研究将为女性缺血性心脏病的病理生理学和预防提供重要信息。

DESCRIPTION (provided by applicant): Acute myocardial infarction (MI) is a major cause of death in American women as it is in men, but despite recent scientific advances, it is unclear whether its pathophysiology differs between women and men. Young and middle-aged (but not older) women have higher mortality and complication rates after an MI compared with men of similar age. The reasons for these differences are unknown; they are not explained by traditional risk factors, comorbidity or treatments, and occur despite that women have less coronary atherosclerosis than men. These findings remain an unsolved issue in the epidemiology of ischemic heart disease in women. Women have a larger burden of psychosocial risk factors. For example, depression is 2 times more frequent in younger (<60 years old) women with MI that than in other groups, affecting up to 40% of this population. Therefore, we hypothesize that psychological stress is a major risk factor in young women with MI and may explain sex differences in MI pathophysiology and prognosis. In about half of patients with ischemic heart disease, myocardial ischemia can be induced by a psychological challenge; this "mental stress ischemia" provides a useful model for the study of psychological stress on cardiac function. In this project we will evaluate sex differences in the prevalence, mechanisms and consequences of mental stress ischemia in young survivors of MI. We will compare 150 women and 150 men <60 years of age who were hospitalized for MI in the previous 6 months. We will also compare the MI patients with 60 female and 60 male community controls without MI. We will test the hypothesis that, among young subjects with MI, mental stress ischemia is a stronger risk factor in women than men, due to heightened physiological and behavioral responses to stress in women with MI relative to men with MI and relative to women without MI. The aims of this study are: (1) Using single photon emission tomography (SPECT) [Tc-99m]sestamibi imaging of myocardial perfusion, compare myocardial perfusion at rest, during mental stress and during exercise stress between women and men less than 60 years old who were hospitalized for a confirmed MI in the previous 6 months. (2) Compare acute vascular and inflammatory responses to stress between young women and men with MI, and between young women and men with MI and their respective community controls. We will examine changes between rest and mental stress in peripheral vascular function, systemic inflammation and immune function measures, and, secondarily, changes in neuroendocrine and behavioral measures. (3) Compare long-term (6-month) vascular and inflammatory outcomes in young women and men with MI. Our proposal will fill a significant gap. Younger women with an MI remain an understudied group despite their higher rate of adverse events compared with men, and may be especially vulnerable to psychological stress. Investigation of this group will provide critical information for the pathophysiology and prevention of ischemic heart disease in women.