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的总体目标是研究糖尿病的患病率、发病率、病理生理学和预测因素。 南亚人群中有无“传统”的亚临床和临床血管和心肌疾病 心血管疾病(CVD)。在对增长的贡献者的理解上存在着公认的差距 南亚人动脉粥样硬化性心血管疾病(ASCVD)和心力衰竭(HF)的风险，这是一个年轻的高危人群 年龄，尽管体重指数相对较低，而且2型糖尿病、血脂异常的发病率很高， 高血压和肝脏脂肪变性。低估ASCVD风险评估的现有预测算法 南亚人的风险。心力衰竭的患病率，包括减少的心力衰竭(HFrEF)和保存的心力衰竭(HFpEF) 在这一人群中，射血分数也在上升。然而，很少有以人群为基础的研究 南澳人群中可获得的纵向数据。在Precision-CARRS的项目1中，我们将利用和构建 根据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，保留率高， 生物储存库。我们建议再进行5年的随访，仔细进行表型分析，并积累 到2025年，估计有167,725人年的随访，估计约有1,000例ASCVD事件和约900例心衰 案子。在目标1中，我们将研究亚临床血管疾病的发病率和不良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关联。我们的目标是 开发南亚特有的预测算法，并在独立的队列中进行验证。亚临床 疾病测量包括动脉僵硬、冠状动脉钙化积分(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。 亚临床的收缩和/或舒张期左心功能不全将使用超声心动图和心衰分期进行测量。 C/D(HFrEF/HFpEF)测定用于临床事件。我们的目标是开发南亚特有的预测性 用于高频的算法。在目标3中，我们将确定高级血脂测量、高级 代谢测量，包括肝脏脂肪测量和特定病理生理通路的激活 存在(I)亚临床血管疾病和(Ii)心肌疾病，以及(Iii)发生不良ASCVD和心衰 事件。将从循环蛋白生物标志物中估计病理生理通路的激活 (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的自然历史来增加现有队列的科学价值 从而为在这一高危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.