Lipoprotein Metabolism and Excess Cardiometabolic Risk in South Asians

南亚人的脂蛋白代谢和过度心脏代谢风险

• 批准号: 10705254
• 负责人: Anand Kumar Rohatgi
• 金额: $ 66.49万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705254
• 关键词: Adipose tissue; African ancestry; Anti-Inflammatory Agents; Antiatherogenic; Asian population; Atherosclerosis; Bangladesh; Black race; Blood Vessels; Body mass index; Calcium; Canada; Cardiometabolic Disease; Cardiovascular system; Carotid Artery Plaques; Chinese; Communities; Diabetes Mellitus; Diet; Diffuse; Ethnic Population; European; Fatty acid glycerol esters; Functional disorder; Glucose Intolerance; Goals; Health Benefit; Heart; Heart Diseases; Hepatic; High Density Lipoproteins; Hispanic; Impairment; India; Individual; Insulin Resistance; Intervention; Leptin; Life Style; Link; Lipids; Lipoproteins; Longitudinal cohort; Measures; Mediator; Metabolic; Metabolism; Minority Groups; Molecular Profiling; Multi-Ethnic Study of Atherosclerosis; National Heart, Lung, and Blood Institute; Nepal; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Observational Study; Outcome; Pakistan; Participant; Pathway Analysis; Pathway interactions; Pattern; Pericardial body location; Phenotype; Predisposition; Prevalence; Prevention Guidelines; Proteomics; Public Health; Risk; Risk Factors; Role; South Asian; Sri Lanka; System; Triglycerides; Validation; Very low density lipoprotein; Visceral; adiponectin; atherosclerosis risk; biobank; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; clinical biomarkers; cohort; coronary artery calcium; diabetes risk; enhancing factor; high risk; improved; insight; insulin sensitivity; lipid metabolism; metabolic phenotype; metabolome; metabolomics; mortality; novel; premature; prevent; recruit; resistin; reverse cholesterol transport; specific biomarkers; subcutaneous; trait; waist circumference

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.

项目概要 南亚个人 (SA)（来自印度、巴基斯坦、孟加拉国、斯里兰卡和印度的个人） 尼泊尔）患动脉粥样硬化性心血管疾病（ASCVD）的风险显着增加， 与非西班牙裔人相比，过早出现胰岛素抵抗，患 2 型糖尿病的风险更高 白人和其他群体已正式宣布。 在 2018 年 ACC/AHA 预防中将南澳种族视为“风险增强因素” 指南2 以及英国使用的 QRISK2/3 风险计算器 降低 ASCVD 风险 SA 中 ASCVD 的死亡率是一个明确的优先事项，但我们的团队有未满足的需求。 脂质代谢的先进措施（保护性和不利性） 优于传统危险因素和传统脂质（非 HDL-C、HDL-C 和甘油三酯） 这些先进措施主要在预测 ASCVD 风险方面进行了研究。 欧洲和非洲裔，但不是 SA。我们的总体目标是提高。 SA 中的心脏代谢风险 该项目的具体目标是确定是否存在。 脂蛋白代谢的先进测量方法解释了 SA 中过度的心脏代谢风险。 我们将在美国生活的 SA 中利用 NHLBI 支持的动脉粥样硬化调节剂 (MASALA)，美国最大的纵向队列，具有广泛的心脏代谢特征 表型分析 (N=1,164) 并将这些发现与类似表型的白人、黑人、 动脉粥样硬化多种族研究（MESA， N=6814）我们将利用英国生物库来确定 SA 和的代谢组学特征。 事件 ASCVD 和糖尿病（N=8,762 名 SA 与 472,780 名欧洲人）。 脂蛋白代谢的高级测量与代谢表型之间的关联 SA 目标 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：确定南亚人与非南亚人相比的代谢组特征 关于心脏代谢表型，拟议的研究有望提供。 对脂蛋白的高级保护措施和不利措施之间的联系的重要见解 SA 中的代谢和过度心脏代谢风险，最终可能会带来更好的临床效果 SA 特异的生物标志物以及针对这些脂蛋白标志物的新型干预措施 鉴于 SA 中 ASCVD 和糖尿病的负担过重，该提案可能会产生影响。 对于这个研究较少但高风险的族群来说，公共卫生有很大好处。