Sun Yan V, Liu Chang, Staimez Lisa, Ali Mohammed K, Chang Howard, Kondal Dimple, Patel Shivani, Jones Dean, Mohan Viswanathan, Tandon Nikhil, Prabhakaran Dorairaj, Quyyumi Arshed A, Narayan K M Venkat, Agrawal Anurag
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
Department of Biomedical Informatics, School of Medicine, Emory University, Atlanta, GA, 30322, USA.
Wellcome Open Res. 2021 May 20;5:255. doi: 10.12688/wellcomeopenres.16336.2. eCollection 2020.
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.
心血管疾病（CVD）是南亚地区的主要死因，在过去二十年中，高血压、2型糖尿病（T2DM）和高脂血症的患病率迅速上升。动脉粥样硬化性心血管疾病（ASCVD）在南亚人生命早期且体重较低时就会发生，传统风险因素的差异负担并不能完全解释这一现象。心力衰竭（HF）是一种复杂的临床综合征，具有异质性结构表型，包括两种主要临床亚型，射血分数保留的心力衰竭（HFpEF）和射血分数降低的心力衰竭（HFrEF）。南亚人心力衰竭的患病率也随着其他代谢疾病的增加而上升，与白人相比，南亚人HFpEF发病年龄更小，体重指数更低。最近关于ASCVD和HF的全基因组关联研究、表观基因组全关联研究和代谢组学研究已经确定了与心血管疾病特征相关的基因、代谢物和途径。然而，这些发现大多是由欧洲血统的样本驱动的，这可能无法在分子水平上准确反映心血管疾病风险以及南亚人独特的心血管疾病风险特征。这种偏差在制定假设驱动的研究时，可能会遗漏南亚人特有的重要因果或预测因素。重要的是，多组学标记的纵向设计可以捕捉与心血管疾病相关的生命历程风险和自然史，并部分解开风险因素、多组学标记与亚临床和临床ASCVD及HF之间的假定因果关系。总之，将高分辨率非靶向代谢组学与严格的纵向设计的表观基因组学相结合，将为南亚人亚临床和临床心血管疾病提供全面、无偏的分子特征描述。对心血管疾病相关代谢组学特征的深入理解，以及表观基因组学和基因组学的进展，将导致对心血管疾病进展的更准确估计，并激发改善心血管健康的新策略。
