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

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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.