Mental Stress Ischemia: Prognosis and Genetic Influences

描述(由申请者提供)：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)原因机制的新数据，确定新的易患MSI的内表型，确定MSI在多样化和当代稳定性冠状动脉疾病(CAD)患者群体中的临床重要性，并确定可能使个人面临MSI风险增加的基因变异。该计划项目将由三个项目和三个核心组成。我们将对650名参与者进行广义CAD研究。我们建议研究雨、遗传、血管、激素和行为与MSI的相关性，以及它们在未来心脏事件中的潜在作用。该项目将带来与微血管内凝血机制相关的新知识，这可能对成功治疗这一现象的能力产生巨大影响。 项目1：精神应激性缺血：预后和遗传影响。Sheps博士将研究MSI与心血管结果之间的关系，以及遗传因素在MSI易感性中的作用。他将对所有650名患者进行锻炼和精神压力测试、基因研究和后续研究。 项目2：心理应激时的血管反应。阿尔谢德·奎尤米博士将研究血管机制，即异常的血管反应性和促炎反应，因为它们与精神应激和MSI有关。他将检测同一队列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。研究将在随访的第二年重复进行，以评估对疾病进展的潜在影响。 项目3：抑郁症和精神应激性脑缺血：大脑机制。维奥拉·瓦卡里诺博士将研究大脑机制，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名患者的子组中进行脑成像和神经内分泌评估。这些研究将得到一个行政和实验室核心、一个成像核心以及一个生物统计和数据管理核心的支持。从这个计划项目中获得的知识应该会导致 公共卫生相关性：这项研究有可能确定基因变异、血管异常和神经心理特征，这些因素会使个人处于精神应激性缺血的高风险状态，从而导致不良后果。如果成功，这项研究将对个性化医疗这一新领域的发展做出重大贡献，在这一领域中，高危个人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.