Lipoprotein Metabolism and Excess Cardiometabolic Risk in South Asians

项目摘要 南亚个人(SA)(来自印度、巴基斯坦、孟加拉国、斯里兰卡和 尼泊尔)显著增加了动脉粥样硬化性心血管疾病(ASCVD)的风险， 过早的胰岛素抵抗，与非西班牙裔相比，患2型糖尿病的风险更高 白人个人和其他群体。全球心血管学界正式宣布 在2018年ACC/AHA预防中将SA种族确认为“风险增加因素” 指南2以及英国使用的QRISK2/3风险计算器中使用的降低ASCVD风险 在SAS中，ASCVD的死亡率是一个明确的优先事项，也是一个尚未得到满足的需求。我们队有 证明了高级脂代谢措施(保护性和不利的)是 优于传统危险因素和常规血脂(非高密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯) 在预测ASCVD风险方面。这些先进的措施主要在以下方面进行了研究 欧洲人和非洲人后裔，但不是SA人。我们的总体目标是改进 SAS患者存在心脏代谢风险。该项目的具体目标是确定是否 脂蛋白代谢的高级测量解释了SAS患者过度心脏代谢的风险。 我们将利用NHLBI支持的动脉粥样硬化介体在美国生活的SAS患者中的作用 (Masala)，美国SAS中最大的纵向队列，有广泛的心脏代谢 表型(N=1,164)，并将这些发现与类似表型的白色，黑色， 西班牙裔和中国人参与了动脉粥样硬化的多种族研究(MESA， N=6814)。我们将利用英国生物库来确定SAS和 ASCVD和糖尿病(N=8,762名SAS与472,780名欧洲人)。目标1：确定 脂蛋白代谢高级指标与代谢表型的相关性 在SAS中。目的2：确定高级脂蛋白指标之间的联系 SAS患者的代谢和亚临床斑块的流行和进展以及ASCVD的发生率。 具体目标3：确定南亚人与非SAS人的代谢特征 关于心脏代谢表型。拟议的研究预计将提供 对脂蛋白高级保护措施和不利措施之间联系的关键见解 SAS患者的代谢和过度心脏代谢风险，并可能最终导致更好的临床 针对SA的生物标记物以及针对这些脂蛋白标记物的新干预 在SAS中。考虑到ASCVD和糖尿病在SAS中的过重负担，这项提议可能会有 对这一研究较少但风险较高的民族来说，巨大的公共健康受益。

Project Summary South Asian individuals (SAs) (individuals from India, Pakistan, Bangladesh, Sri Lanka, and Nepal) have markedly increased risk of atherosclerotic cardiovascular disease (ASCVD), premature insulin resistance, and higher risk of type 2 diabetes compared with non-Hispanic White individuals and other groups. The global cardiovascular community has officially recognized SA ethnicity as a “risk-enhancing factor” in the 2018 ACC/AHA Prevention Guidelines2 as well as in the QRISK2/3 risk calculator used in the U.K. Reducing ASCVD risk and mortality from ASCVD in SAs is a clear priority and unmet need. Our team has demonstrated that advanced measures of lipid metabolism (protective and adverse) are superior to traditional risk factors and conventional lipids (non-HDL-C, HDL-C, and triglycerides) in predicting ASCVD risk. These advanced measures have been studied primarily in those of European and African descent but not among SAs. Our overall goal is to improve cardiometabolic risk in SAs. The specific objective of this project is to determine whether advanced measures of lipoprotein metabolism explain the excess cardiometabolic risk in SAs. We will leverage the NHLBI-supported Mediators of Atherosclerosis in SAs Living in America (MASALA), the largest longitudinal cohort of U.S. SAs with extensive cardiometabolic phenotyping (N=1,164) and compare these findings to similarly phenotyped White, Black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA, N=6814). We will utilize the UK Biobank to ascertain metabolomic signatures of SAs and incident ASCVD and diabetes (N=8,762 SAs vs. 472,780 Europeans). Aim 1: Determine the association between advanced measures of lipoprotein metabolism and metabolic phenotypes in SAs. Aim 2: Determine the association between advanced measures of lipoprotein metabolism and subclinical plaque prevalence and progression and incident ASCVD in SAs. Specific Aim 3: Determine the metabolomic signatures of South Asians compared to non-SAs with respect to cardiometabolic phenotypes. The proposed studies are expected to provide critical insights into the link between advanced protective and adverse measures of lipoprotein metabolism and excess cardiometabolic risk in SAs and may eventually lead to better clinical biomarkers specific to SAs as well as to novel interventions targeting these lipoprotein markers in SAs. Given the excessive burden of ASCVD and diabetes in SAs, this proposal may have a large public health benefit to this less studied but high-risk ethnic group.