Mental Stress Ischemia: Prognosis and Genetic Influences

描述（申请人提供）：该计划项目的总体长期目标是生成关于精神应激性缺血（MSI）的因果机制的新数据，以识别易受MSI影响的新内在表型，以确定MSI在患有稳定性冠状动脉疾病（CAD）的多样化和当代患者人群中的临床重要性，并确定可能使个体MSI风险增加的基因型变异。该项目将由三个项目和三个核心组成。我们将研究650名患有广泛定义的CAD的参与者。我们建议检查雨，遗传，血管，激素和行为相关的MSI和他们的潜在作用，在未来的心脏事件。该项目将导致与MSI机制相关的新知识，这可能对成功治疗这种现象的能力产生巨大影响。 项目1：精神应激缺血：预后和遗传影响。Sheps博士将研究MSI与心血管结局之间的关系以及遗传因素对MSI易感性的作用。他将对所有650名患者进行运动和精神压力测试、遗传研究和随访研究。 项目2：精神压力下的血管反应。Arshed Quyyumi博士，PI，将研究血管机制，即，异常的血管反应性和促炎反应，因为它们与精神压力和MSI有关。他将检查同一组患者在精神压力下的外周血管功能，以及80名患者的冠状动脉血管反应。研究将在第2年随访时重复进行，以评估对疾病进展的潜在影响。 项目3：抑郁症和精神应激缺血：脑机制。维奥拉·瓦卡里诺博士，PI，将研究大脑机制，重点是与抑郁症相关的神经生物学途径。她将在整个PPG人群中研究抑郁症和MSI之间的联系，并将在160名患者的亚组中进行脑成像和神经内分泌评估。这些研究将得到行政和实验室核心、成像核心以及生物统计和数据管理核心的支持。从这个项目中获得的知识应该导致 公共卫生相关性：这项研究有可能确定遗传变异，血管异常和神经心理学特征，这些特征使个体处于发展精神应激缺血的高风险中，从而产生不良后果。如果成功，这项研究将为个性化医疗新领域的发展做出重要贡献，在个性化医疗中，高风险个体可以在疾病过程的早期被识别出来，并有针对性地进行预防性干预。

DESCRIPTION (provided by applicant): The overall long range goal of this program project is to generate novel data on the causal mechanisms of mental stress ischemia (MSI), to identify new endophenotypes susceptible to MSI, to determine the clinical importance of MSI in a diverse and contemporary patient population with stable coronary artery disease (CAD), and to identify genotype variants that may put individuals at increased risk for MSI. This program project will consist of three projects and three cores. We will study 650 participants with broadly defined CAD. We propose to examine rain, genetic, vascular, hormonal, and behavioral correlates of MSI and their potential role in future cardiac events. This project will lead to new knowledge related to the mechanisms of MSI which could have tremendous influence on the ability to successfully treat this phenomenon. Project 1: Mental Stress Ischemia: Prognosis and Genetic Influences. Dr. Sheps, PI, will study the relationship between MSI and cardiovascular outcomes and the role of genetic factors on MSI susceptibility. He will perform exercise and mental stress testing, genetic studies and follow up studies on all 650 patients. Project 2: Vascular Responses During Mental Stress. Dr. Arshed Quyyumi, PI, will study vascular mechanisms, i.e., abnormal vascular reactivity and pro-inflammatory responses as they relate to mental stress and MSI. He will examine peripheral vascular function in the same cohort of patients during mental stress, and coronary vascular responses in a sub group of 80 patients. Studies will be repeated at year two of follow-up to assess potential influences on disease progression. Project 3: Depression and Mental Stress Ischemia: Brain Mechanisms. Dr. Viola Vaccarino, PI, will study brain mechanisms, with a focus on neurobiological pathways related to depression. She will examine the link between depression and MSI in the whole PPG population and will perform brain imaging and neuroendocrine assessments in a subgroup of 160 patients. These studies will be supported by an Administrative and Laboratory Core, an Imaging Core, and a Biostatistics and Data Management Core. The knowledge gained from this program project should lead to PUBLIC HEALTH RELEVANCE: This research has potential to identify genetic variants, vascular abnormalities and neuropsychological features that place individuals at high risk for development of mental stress ischemia and therefore adverse outcomes. If successful, this research will contribute in significant ways to the development of the new field of personalized medicine in which individuals at high risk can be identified early in the disease process and targeted for preventative interventions.