Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential burden of conventional risk factors. Heart failure (HF) is a complex clinical syndrome of heterogeneous structural phenotypes including two major clinical subtypes, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). The prevalence of HF in South Asians is also rising with other metabolic diseases, and HFpEF develops at younger age and leaner body mass index in South Asians than in Whites. Recent genome-wide association studies, epigenome-wide association studies and metabolomic studies of ASCVD and HF have identified genes, metabolites and pathways associated with CVD traits. However, these findings were mostly driven by samples of European ancestry, which may not accurately represent the CVD risk at the molecular level, and the unique risk profile of CVD in South Asians. Such bias, while formulating hypothesis-driven research studies, risks missing important causal or predictive factors unique to South Asians. Importantly, a longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multi-omic markers and subclinical and clinical ASCVD and HF. In conclusion, combining high-resolution untargeted metabolomics with epigenomics of rigorous, longitudinal design will provide comprehensive unbiased molecular characterization of subclinical and clinical CVD among South Asians. A thorough understanding of CVD-associated metabolomic profiles, together with advances in epigenomics and genomics, will lead to more accurate estimates of CVD progression and stimulate new strategies for improving cardiovascular health.
Highlights
Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades
A longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multiomic markers and subclinical and clinical Atherosclerotic CVD (ASCVD) and Heart failure (HF)
The prevalence of HF in South Asians is rising with other metabolic diseases[29,30], and HFpEF develops at younger age and leaner BMI than for Whites[31]
Summary
The molecular functions of identified epigenetic and metabolic markers, key genes and pathways involved in subclinical and clinical CVD will help us develop future targeted studies to improve comorbid disease prevention and clinical care strategies. To extend this understanding to high-risk populations such as South Asians, it is important that such studies be performed in longitudinal cohorts that adequately represent the ethnicity and the environment. Since the multi-omics profile (e.g., epigenome and metabolome) can be modified by dynamic and cumulative environmental factors, capturing the longitudinal multi-omics would benefit the understanding of risk development and progression of subclinical and clinical CVD in South Asians. Incorporating these multi-omic profiles can optimize the diagnosis, treatment and prognosis of CVD, which is the most important and still growing health burden for South Asian populations
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