Mental Stress Ischemia: Prognosis and Genetic Influences

精神应激缺血：预后和遗传影响

基本信息

批准号：
8527948
负责人：
ARSHED A QUYYUMI
金额：
$ 2.08万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8527948
关键词：
Acute Address Adenosine Adrenergic Receptor Alleles Behavioral Biometry Blood Vessels Brain Brain Ischemia Brain imaging Candidate Disease Gene Cardiac Cardiovascular system Categories Cessation of life Chronic Clinical Coronary Coronary Arteriosclerosis Coronary Artery Bypass Data Development Disease Disease Progression Event Exercise Follow-Up Studies Frequencies Future General Population Genetic Genetic Polymorphism Genotype Goals Health Hormonal Hospitalization Human Image Individual Inflammatory Response Intervention Ischemia Knowledge Laboratories Lead Link Medicine Mental Depression Myocardial Infarction Neurobiology Neurosecretory Systems Operative Surgical Procedures Outcome Participant Pathway interactions Patients Peripheral Population Predisposition Process Psyche structure Psychological Stress Rain Research Risk Role Stratification Stress Stress Tests Subgroup Sudden Death Unstable angina Variant Viola adverse outcome biological adaptation to stress cohort data management endophenotype follow-up genetic variant high risk indexing mental development neuropsychological novel outcome forecast patient population prognostic programs response

项目摘要

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.

描述（由申请人提供）：该计划项目的总体长期目标是生成有关精神应激缺血（MSI）因果机制的新数据，识别易受 MSI 影响的新内表型，确定 MSI 在精神应激缺血中的临床重要性。患有稳定型冠状动脉疾病 (CAD) 的多样化和当代患者群体，并识别可能使个体面临 MSI 风险增加的基因型变异。该计划项目将由三个项目、三个核心组成。我们将使用广泛定义的 CAD 对 650 名参与者进行研究。我们建议检查 MSI 的降雨、遗传、血管、激素和行为相关性及其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。首席研究员 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、基因研究和后续研究。项目 2：精神压力期间的血管反应。首席研究员 Arshed Quyyumi 博士将研究血管机制，即异常血管反应性和促炎症反应，因为它们与精神压力和 MSI 相关。他将检查同一组患者在精神压力期间的外周血管功能，以及 80 名患者的亚组的冠状血管反应。将在随访的第二年重复研究，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：大脑机制。 PI 维奥拉·瓦卡里诺 (Viola Vaccarino) 博士将研究大脑机制，重点关注与抑郁症相关的神经生物学途径。她将检查整个 PPG 人群中抑郁症与 MSI 之间的联系，并对 160 名患者的亚组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。从该计划项目中获得的知识应该导致公共卫生相关性：这项研究有可能识别遗传变异、血管异常和神经心理学特征，这些特征使个体处于发生精神应激缺血并因此产生不良后果的高风险中。如果成功，这项研究将为个性化医疗新领域的发展做出重大贡献，在该领域，可以在疾病过程的早期识别出高危个体，并有针对性地进行预防性干预。