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; 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.

项目摘要 南亚个人（SAS）（来自印度，巴基斯坦，孟加拉国，斯里兰卡和 尼泊尔）明显增加了动脉粥样硬化心血管疾病（ASCVD）的风险， 与非西班牙裔相比，早产胰岛素抵抗和较高的2型糖尿病风险 白人和其他群体。全球心血管社区已正式 在2018年ACC/AHA预防中，公认的SA种族是“增强风险因素” 指南2以及英国使用的QRISK2/3风险计算器降低ASCVD风险 SAS中ASCVD的死亡率是明确的优先事项和未满足的需求。我们的团队有 证明脂质代谢的高级度量（保护性和不良）是 优于传统危险因素和常规脂质（非HDL-C，HDL-C和甘油三酸酯） 在预测ASCVD风险时。这些高级措施主要是研究 欧洲和非洲血统，但不在SAS中。我们的总体目标是改善 SAS中的心脏代谢风险。该项目的具体目标是确定是否 脂蛋白代谢的高级度量解释了SAS中过量的心脏代谢风险。 我们将利用居住在美国的SAS中的NHLBI支持的动脉粥样硬化的介体 （Masala），美国SA的最大纵向队列，具有广泛的心脏代谢 表型（n = 1,164），并将这些发现与类似表型的白色，黑色， 西班牙裔和中国参与者从事动脉粥样硬化多民族研究（Mesa， n = 6814）。我们将利用英国生物库来确定SAS和 事件ASCVD和糖尿病（n = 8,762 SAS与472,780欧洲人）。目标1：确定 脂蛋白代谢和代谢表型的高级度量之间的关联 在SAS。目标2：确定脂蛋白高级度量之间的关联 SAS中的代谢和亚临床斑块患病率，进展以及入射ASCVD。 特定目的3：与非SAS相比，确定南亚人的代谢组性特征 关于心脏代谢表型。拟议的研究预计将提供 对脂蛋白的高级保护和不良测量之间的联系的关键见解 代谢并超过SAS的心脏代谢风险，最终可能导致更好的临床 针对SAS的生物标志物以及针对这些脂蛋白标记的新干预措施 在SAS。鉴于SAS中ASCVD和糖尿病的过量燃烧，该建议可能具有 大型公共卫生对这个较少研究但高风险的族裔有益。