Prevalence, Incidence, and Predictors of Subclinical and Clinical Vascular and Myocardial Disease: Pathophysiologic Pathways

项目摘要/摘要：项目 1 项目 1 的总体目标是研究以下疾病的患病率、发病率、病理生理学和预测因素： 有或没有“传统”的南亚个体的亚临床和临床血管和心肌疾病 心血管疾病（CVD）。在理解增加的贡献者方面存在着众所周知的差距 南亚人的动脉粥样硬化 CVD (ASCVD) 和心力衰竭 (HF) 风险是年轻人群的高风险人群 年龄，尽管体重指数相对较低，并且 2 型糖尿病、血脂异常、 高血压、肝脂肪变性。用于评估低估 ASCVD 风险的可用预测算法 南亚人面临的风险。心力衰竭的患病率，包括减少的心力衰竭 (HFrEF) 和保留的心力衰竭 (HFpEF) 该人群的射血分数也在上升。然而，基于人群的研究却很少 SA 人群中可用的纵向数据。在 Precision-CARRS 项目 1 中，我们将利用并构建 凭借独特的资源和科学机会，正在进行的降低心脏代谢风险中心 南亚 (CARRS) 队列由 NHLBI 资助建立，有 21,864 名社区参与者 代表印度两个城市，这两个城市已被跟踪长达 10 年，保留率很高，并且 生物储存库。我们建议进行额外 5 年的随访，并进行仔细的表型分析并积累 到 2025 年估计将有 167,725 人年的随访，估计约有 1,000 例 ASCVD 事件和约 900 例 HF 案例。在目标 1 中，我们将研究亚临床血管疾病的患病率和不良 ASCVD 的发生率 事件及其与纵向获取的 ASCVD 和代谢危险因素数据的关联。我们的目标是 开发南亚特有的预测算法并在独立队列中验证它们。亚临床 疾病测量包括动脉僵硬度、冠状动脉钙化评分 (CAC)、颈动脉内膜中层厚度 （CIMT）和颈动脉斑块。在目标 2 中，我们将确定亚临床左心室 (LV) 的患病率 功能障碍和临床心力衰竭及其与纵向测量的 ASCVD 和代谢危险因素的关系。 将使用超声心动图和心力衰竭分期来测量亚临床收缩期和/或舒张期左心室功能障碍 C/D (HFrEF / HFpEF) 确定临床事件。我们的目标是开发南亚特有的预测 HF 算法。在目标 3 中，我们将确定高级血脂测量值、高级血脂测量值和高级血脂测量值之间的关系。 代谢测量，包括肝脂肪测量和特定病理生理途径的激活 以及存在 (i) 亚临床血管疾病和 (ii) 心肌疾病，以及 (iii) 意外发生的不良 ASCVD 和心力衰竭 事件。病理生理途径的激活将根据循环蛋白质生物标志物进行估计 （炎症、免疫失调、血栓形成、心肌缺血/拉伸）。我们的总体目标是 通过定义南方 ASCVD 和 HF 的自然史，增强现有队列的科学价值 亚洲人，从而为在这一高风险人群中开发预测算法铺平了道路。

PROJECT SUMMARY / ABSTRACT: Project 1 The overarching goal of Project 1 is to study the prevalence, incidence, pathophysiology and predictors of sub-clinical and clinical vascular and myocardial disease in South Asian individuals with and without “traditional” cardiovascular disease (CVD). There are well-recognized gaps in understanding contributors to the increased atherosclerotic CVD (ASCVD) and heart failure (HF) risk in South Asians, a population at high risk at a younger age, despite relatively low body mass index, and with a high prevalence of type 2 diabetes, dyslipidemia, hypertension, and hepatic steatosis. Available predictive algorithms for evaluation of risk under-estimate ASCVD risk in South Asians. The prevalence of HF, including both HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction is also rising in this population. However, there are few population-based studies with longitudinal data available in the SA population. In Project 1 of Precision-CARRS, we will leverage and build upon a unique resource and scientific opportunity, the ongoing Center for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort, established with NHLBI funding, with 21,864 community-based participants representative of two cities in India who have been followed for up to 10 years with high retention rates and a biorepository. We propose to perform an additional 5 years of follow-up with careful phenotyping and accrue an estimated 167,725 person-years of follow-up by 2025 with an estimated ~1,000 incident ASCVD and ~900 HF cases. In Aim 1, we will study the prevalence of subclinical vascular disease and incidence of adverse ASCVD events and their associations with longitudinally acquired ASCVD and metabolic risk factor data. We aim to develop South Asian-specific predictive algorithms and validate them in independent cohorts. Sub-clinical disease measures include arterial stiffness, coronary artery calcium score (CAC), carotid intima-media thickness (CIMT) and carotid plaque. In Aim 2, we will determine the prevalence of subclinical left ventricular (LV) dysfunction and clinical HF and their relationship with longitudinally measured ASCVD and metabolic risk factors. Sub-clinical systolic and/or diastolic LV dysfunction will be measured using echocardiography and HF Stages C/D (HFrEF / HFpEF) determined for clinical events. Our goal is to develop South Asian-specific predictive algorithms for HF. In Aim 3, we will determine the relationship between advanced lipid measures, advanced metabolic measures, including hepatic fat measurements and activation of specific pathophysiologic pathways and the presence of (i) sub-clinical vascular and (ii) myocardial disease, and (iii) incident adverse ASCVD and HF events. Activation of pathophysiologic pathways will be estimated from circulating protein biomarkers (inflammation, immune dysregulation, thrombogenesis, myocardial ischemia/stretch). Our overall goal is to augment the scientific value of the existing cohort by defining the natural history of ASCVD and HF in South Asians, thus paving the way for developing predictive algorithms in this high-risk population.