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

项目总结/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： 南亚人亚临床和临床血管和心肌疾病，有和没有“传统” 心血管疾病（CVD）。在了解造成日益增加的人口贩运的因素方面， 在南亚人中，动脉粥样硬化性CVD（ASCVD）和心力衰竭（HF）风险，这是一个年轻人中的高风险人群。 年龄，尽管体重指数相对较低，2型糖尿病，血脂异常， 高血压和肝脂肪变性。用于评估风险的现有预测算法低估ASCVD 南亚人的风险HF的患病率，包括HF降低（HFrEF）和HF保留（HFpEF） 射血分数在这一人群中也在上升。然而，很少有基于人群的研究， SA人群中的纵向数据。在Precision-CARRS的项目1中，我们将利用和构建 在一个独特的资源和科学机会，正在进行的心脏代谢风险降低中心， 南亚（CARRS）队列，由NHLBI资助建立，有21，864名社区参与者 印度两个城市的代表，他们被跟踪长达10年，保持率高， 生物储藏室我们建议进行额外的5年随访，仔细进行表型分析， 估计到2025年随访167，725人年，估计约1，000例ASCVD和约900例HF事件 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。 事件及其与纵向获得的ASCVD和代谢危险因素数据的相关性。我们的目标是 开发南亚特定的预测算法，并在独立的队列中验证它们。亚临床 疾病测量包括动脉硬度、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） 功能障碍和临床HF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HF分期测量亚临床收缩和/或舒张LV功能障碍 确定临床事件的C/D（HFrEF / HFpEF）。我们的目标是开发南亚特定的预测性 HF算法在目标3中，我们将确定先进的血脂指标，先进的 代谢测量，包括肝脏脂肪测量和特定病理生理途径的激活 以及是否存在（i）亚临床血管和（ii）心肌疾病，以及（iii）偶发不良ASCVD和HF 事件将根据循环蛋白质生物标志物估计病理生理途径的激活 （炎症、免疫失调、血栓形成、心肌缺血/牵张）。我们的总体目标是 通过定义南方ASCVD和HF的自然史来增加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.