Precision Cardiovascular Diseases Phenotyping and Pathophysiological Pathways in the CARRS Cohort (Precision-CARRS)

CARRS 队列中的精密心血管疾病表型和病理生理学途径 (Precision-CARRS)

• 批准号: 10622446
• 负责人: Kabayam M Venkat Narayan
• 金额: $ 228.97万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622446
• 关键词: Adult; Age; Air; Air Pollution; Asia; Atherosclerosis; Automobile Driving; Behavior; Behavioral; Biological; Body Weight; Cardiomyopathies; Cardiovascular Diseases; Caring; Cessation of life; Clinical; Collaborations; Complex; Coupling; Data; Data Analyses; Data Analytics; Data Collection; Detection; Development; Diabetes Mellitus; Disease; Disease Outcome; Disease Pathway; Dyslipidemias; Environmental Exposure; Epidemiology; Etiology; Event; Fatty Liver; Functional disorder; Funding; Future; Genetic; Goals; Health behavior; Heart Diseases; Heart failure; Heterogeneity; Humanities; Hybrids; Immune System Diseases; Incidence; India; Individual; Inflammation; Investigation; Knowledge; Lead; Longitudinal cohort; Maps; Measures; Mediating; Molecular; Myocardial Infarction; National Heart, Lung, and Blood Institute; Natural History; Outcome Study; Pathogenicity; Pathway interactions; Pattern; Persons; Phenotype; Population; Population Heterogeneity; Prevalence; Prevention; Program Research Project Grants; Proteins; Research; Research Personnel; Resource Sharing; Resources; Risk; Risk Factors; Risk Reduction; Role; Sampling; Signal Transduction; Social Behavior; South Asian; Stroke; Thinness; Time; Variant; Vascular Diseases; acquired factor; aged; behavior influence; biobank; built environment; cardiometabolic risk; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical phenotype; cohort; coronavirus disease; data management; design; diabetes risk; disease diagnostic; disease phenotype; disorder risk; follow-up; health assessment; heart disease risk; high risk; high risk population; improved; innovation; insight; mortality; multiple omics; population based; prevent; programs; protein biomarkers; public health relevance; recruit; retention rate; risk prediction; social factors; social influence

PROJECT SUMMARY / ABSTRACT (Overall) Precision-CARRS will revolutionize the cardiovascular disease (CVD) prevention and care paradigm from imprecise prediction with focus on late stage disease to personalized and precise prediction with improved understanding of early-stage disease to maintain cardiovascular health. Atherosclerotic CVD (ASCVD) and heart failure (HF) phenotypes are heterogeneous and result from complex interactions between immutable genetic factors and mutable forces operating at environmental (e.g., ambient air quality), individual (e.g., health behaviors, social influence), and molecular (e, g, proteins, 'omics) levels. South Asians are an understudied population at high CVD risk even at young ages, at low body weight, and in the absence of traditional risk factors. We will leverage substantial matched resources, and also build upon the NHLBI- funded CARRS cohort, a representative sample of n=21,864 South Asians aged ≥ 20 years, with ongoing follow-up for clinical ASCVD risk factors, clinical disease, and mortality. The cohort has high retention (>95% have at least one follow-up) and a biorepository of 360,000 stored samples. We will add detailed subclinical and clinical CVD phenotyping, repeated measures of targeted protein markers and untargeted multi-omics, and real-time assessment of health behaviors. By extending follow-up by an additional 5 years, we will accrue 176,536 person-years of follow up, >1,000 incident ASCVD, and nearly >900 cases of clinical HF (Stages C/D). Enabled by precise mapping of CVD at the granular level of subclinical and clinical phenotypes, we will investigate the epidemiology and causes of CVD along both ASCVD and HF pathways. Three complementary cores (Administrative and Field Coordination; CVD Phenotyping; and Data Management and Analysis) will support four interconnected projects, one of which is led by an early-stage investigator (ESI). All four project examine common subclinical and clinical endpoints from synergistic vantage points: traditional risk factors and targeted protein-based pathophysiological pathways (Project 1), the impact of air pollution and mediating mechanisms (Project 2), molecular signals and mechanisms through integrative untargeted multi-omics (Project 3), and socio-behavioral influences on CVD risk and outcomes studied via spousal dyads (Project 4, ESI). Precision-CARRS will unravel the natural history, pathophysiology, and causal factors of vascular and myocardial disease and pave the way for precision CVD diagnostics, prevention, and care for South Asians–who represent one fifth of humanity and are a rapidly growing sub- population in the US. In summary, Precision-CARRS is designed to be a powerful platform to understand the natural history of CVD in an understudied high-risk population and to spur future innovative scientific collaborations with other CVD longitudinal cohorts in the US and globally.

项目摘要/摘要(总体) Precision-CARRS将彻底改变心血管疾病(CVD)的预防和护理模式 以晚期疾病为重点的不精确预测到个性化和精确化预测 了解早期疾病以维持心血管健康。动脉粥样硬化性心血管疾病(ASCVD)和 心力衰竭(HF)的表型是不同的，并且是不变的 遗传因素和在环境(例如，环境空气质量)、个人(例如， 健康行为、社会影响)和分子水平(例如蛋白质、组学)。南亚人是一个 未充分研究的人群即使在年轻、低体重和缺乏高血压的情况下也有高心血管疾病的风险 传统的风险因素。我们将利用大量的匹配资源，并在NHLBI- 资助的CARRS队列，n=21,864名20岁的≥南亚人的代表性样本，正在进行 临床ASCVD危险因素、临床疾病和死亡率的随访。队列具有较高的保留率(&gt；95% 至少有一次后续行动)和一个储存了360,000份样本的生物库。我们将增加详细的亚临床 和临床CVD表型，靶向蛋白标记物的重复测量和非靶向多组学， 以及健康行为的实时评估。通过将跟进时间再延长5年，我们将 累计176,536人年的随访，&>1,000例ASCVD事件，以及近&>900例临床心衰 (C/D阶段)。通过在亚临床和临床的粒度级别精确绘制CVD地图来实现 表型方面，我们将沿着ASCVD和HF途径调查心血管疾病的流行病学和病因。 三个相辅相成的核心(行政和外地协调；心血管疾病表型；以及数据 管理和分析)将支持四个相互关联的项目，其中一个由早期阶段领导 调查员(ESI)。所有四个项目都从协同的角度检查常见的亚临床和临床终点 要点：传统危险因素和以蛋白质为基础的靶向病理生理途径(项目1)，影响 大气污染与调控机制研究(项目2)、分子信号与调控机制 非靶向多组学(项目3)，以及通过以下方式研究的社会行为对心血管疾病风险和结果的影响 配偶二人组(项目4，ESI)。Precision-CARRS将揭开自然历史、病理生理学和 血管和心肌疾病的病因，并为精确的心血管疾病诊断铺平道路， 预防和照顾南亚人--他们占人类的五分之一，是一个迅速增长的亚 美国的人口。总之，Precision-CARRS旨在成为一个强大的平台，以了解 研究不足的高危人群中心血管疾病的自然历史并激励未来的创新科学 与美国和全球其他心血管疾病纵向队列的合作。