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

项目总结/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， 从关注晚期疾病的不精确预测到个性化和精确预测， 了解早期疾病，以保持心血管健康。动脉粥样硬化性CVD（ASCVD）和 心力衰竭（HF）表型是异质性，是由不可变 遗传因素和在环境中起作用的可变力（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。南亚人是 即使在年轻时，在低体重，在没有 传统风险因素。我们将利用大量的匹配资源，并在NHLBI的基础上， 资助的CARRS队列，n= 21，864例年龄≥ 20岁的南亚人的代表性样本，正在进行 随访临床ASCVD风险因素、临床疾病和死亡率。该队列的保留率较高（>95% 至少有一个后续行动）和360，000个储存样品的生物储存库。我们将添加详细的亚临床 和临床CVD表型，靶向蛋白标记物和非靶向多组学的重复测量， 和健康行为的实时评估。通过将随访时间延长5年，我们将 累计随访176，536人-年，> 1，000例ASCVD事件和近900例临床HF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， 表型，我们将调查流行病学和心血管疾病的原因沿着ASCVD和HF途径。 三个互补的核心（行政和外地协调;心血管疾病表型分析;和数据 管理和分析）将支持四个相互关联的项目，其中一个项目由一个早期阶段的 研究员（ESI）。所有四个项目都从协同的Vantage检查了常见的亚临床和临床终点 点：传统的风险因素和靶向蛋白质为基础的病理生理途径（项目1），影响 空气污染和介导机制（项目2），分子信号和机制，通过整合 非靶向多组学（项目3），以及社会行为对CVD风险和结果的影响， 配偶二人组（项目4，ESI）。Precision-CARRS将揭开自然史，病理生理学， 血管和心肌疾病的病因，并为精确的CVD诊断铺平了道路， 南亚人占人类的五分之一，是一个迅速增长的亚 人口在美国。总之，Precision-CARRS旨在成为了解 在未充分研究的高风险人群中CVD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。

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.