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) 的预防和护理范式 从关注晚期疾病的不精确预测到改进的个性化和精确预测 了解早期疾病以维持心血管健康。 心力衰竭（HF）表型是异质的，是由不可变因素之间复杂的相互作用造成的 环境（例如，环境空气质量）、个体（例如， 健康行为、社会影响）和分子（例如，蛋白质、“组学”）水平是南亚人的一个水平。 未被研究的人群即使在年轻、体重低且缺乏治疗的情况下也具有高 CVD 风险 我们将利用大量匹配资源，并以 NHLBI 为基础。 资助的 CARRS 队列，是 n=21,864 名 20 岁以上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 该队列的保留率很高（>95%）。 至少有一个后续）和一个包含 360,000 个存储样本的生物样本库，我们将添加详细的亚临床样本。 和临床CVD表型、靶向蛋白质标记物和非靶向多组学的重复测量， 通过将随访时间再延长 5 年，我们将实现对健康行为的实时评估。 累计 176,536 人年的随访，超过 1,000 起 ASCVD 事件，以及近超过 900 起临床心力衰竭病例 （阶段 C/D）通过在亚临床和临床的粒度水平上精确绘制 CVD 来实现。 表型，我们将沿着 ASCVD 和 HF 途径研究 CVD 的流行病学和原因。 三个互补的核心（行政和现场协调；CVD 表型分析；和数据 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 所有四个项目都从协同优势检查常见的亚临床和临床终点。 要点：传统的危险因素和基于蛋白质的靶向病理生理途径（项目1），影响 空气污染及其调节机制（项目2）、分子信号和机制的综合研究 非目标多组学（项目 3）以及社会行为对 CVD 风险和结果的影响通过研究 配偶对（项目 4，ESI）将揭示自然历史、病理生理学和 血管和心肌疾病的致病因素，为精确的CVD诊断铺平道路， 为南亚人提供预防和护理服务——南亚人占人类五分之一，是一个快速增长的亚裔群体 总之，Precision-CARRS 旨在成为了解美国人口的强大平台。 CVD 在未被充分研究的高危人群中的自然史，并刺激未来的创新科学 与美国和全球其他 CVD 纵向队列的合作。