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)是美国女性和男性的主要死亡原因，但尽管最近取得了科学进展，其病理生理学是否在女性和男性之间存在差异尚不清楚。与同龄男性相比，年轻和中年(但不是老年)女性心肌梗死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、合并症或治疗方法来解释，尽管女性的冠状动脉粥样硬化比男性少，但仍会发生。这些发现在女性缺血性心脏病的流行病学中仍然是一个悬而未决的问题。女性在心理社会风险因素方面的负担更大。例如，患有心肌梗塞的年轻女性(60岁)抑郁的发生率是其他人群的两倍，影响到高达40%的人群。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。在约半数的缺血性心脏病患者中，心理应激可诱发心肌缺血，这种“心理应激缺血”为研究心理应激对心功能的影响提供了有用的模型。在这个项目中，我们将评估在年轻的MI幸存者中精神应激性缺血的患病率、机制和后果的性别差异。我们将比较前6个月因心肌梗塞住院的150名女性和150名60岁以上的男性。我们还将比较心肌梗死患者与60名女性和60名男性社区对照没有心肌梗塞。我们将检验这一假设，即在患有心肌梗死的年轻受试者中，精神应激缺血是女性比男性更强的风险因素，这是因为患有心肌梗死的女性相对于患有心肌梗死的男性和相对于没有心肌梗死的女性对压力的生理和行为反应更强。本研究的目的是：(1)应用单光子发射断层扫描(SPECT)[~(99)m]Sestamibi心肌灌注显像，比较在过去6个月内因确诊为心肌梗塞而住院的60岁以下的女性和男性在静息、精神应激和运动应激时的心肌血流灌注。(2)比较男女心肌梗死患者、男女心肌梗死患者及其社区对照人群对应激的急性血管反应和炎症反应。我们将考察休息和精神应激在外周血管功能、全身炎症和免疫功能指标上的变化，其次是神经内分泌和行为指标的变化。(3)比较年轻女性和男性心肌梗死患者的长期(6个月)血管和炎症结果。我们的建议将填补一个重大空白。患有心肌梗死的年轻女性仍然是一个研究不足的群体，尽管与男性相比，她们的不良事件发生率更高，而且可能特别容易受到心理压力的影响。对这一群体的研究将为女性缺血性心脏病的病理生理学和预防提供关键信息。

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.