Mental Stress Ischemia: Prognosis and Genetic Influences

描述（由申请人提供）：该项目的总体长期目标是生成关于精神应激性缺血（MSI）因果机制的新数据，确定对MSI易感的新内表型，确定MSI在多样化和当代稳定冠状动脉疾病（CAD）患者群体中的临床重要性，并确定可能使个体增加MSI风险的基因型变异。本项目将由三个项目和三个核心组成。我们将研究650名患有广义CAD的参与者。我们建议研究与MSI相关的降雨、遗传、血管、激素和行为，以及它们在未来心脏事件中的潜在作用。该项目将带来与MSI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。

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