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）患动脉粥样硬化性心血管疾病（ASCVD）的风险显著增加， 过早的胰岛素抵抗，2型糖尿病的风险高于非西班牙裔 白色个体和其他群体。全球心血管社区已正式 在2018年ACC/AHA预防中，将SA种族视为“风险增强因素” 指南2以及英国使用的QRISK 2/3风险计算器。降低ASCVD风险 在SA中ASCVD的死亡率是一个明确的优先事项和未满足的需求。我们的团队已被 表明脂质代谢的先进措施（保护和不利）是 优于传统风险因素和常规血脂（非HDL-C、HDL-C和甘油三酯）的上级 预测ASCVD风险。这些先进的措施主要是在那些 欧洲人和非洲人后裔，但不是SA。我们的总体目标是提高 SA的心脏代谢风险。本项目的具体目标是确定 脂蛋白代谢的先进措施解释了SA中过度的心脏代谢风险。 我们将利用NHLBI支持的动脉粥样硬化在SA生活在美国的调解人 （MASALA），美国SA的最大纵向队列，具有广泛的心脏代谢 表型分型（N= 1，164），并将这些结果与相似表型分型的白色，黑色， 多种族动脉粥样硬化研究（梅萨， N=6814）。我们将利用英国生物库来确定SA的代谢组学特征， ASCVD事件和糖尿病（N= 8，762例SA vs 472，780例欧洲人）。目标1：确定 脂蛋白代谢高级指标与代谢表型之间的相关性 在SA中。目的2：确定脂蛋白高级测量之间的关联 SA中的代谢和亚临床斑块患病率和进展以及ASCVD事件。 具体目标3：确定南亚人与非SA人相比的代谢组学特征 关于心脏代谢表型。预计拟议的研究将提供 对脂蛋白的高级保护和不利措施之间的联系的重要见解 代谢和过度的心脏代谢风险，并可能最终导致更好的临床 SA特异性生物标志物以及靶向这些脂蛋白标志物的新型干预措施 在SA中。考虑到SA中ASCVD和糖尿病的过度负担，该建议可能会导致 这一研究较少但风险较高的族裔群体受益于大量的公共卫生服务。

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.