Metabolic effects and mechanisms for heart failure in South Asians

南亚人心力衰竭的代谢效应和机制

• 批准号: 10642776
• 负责人: ALKA M. KANAYA
• 金额: $ 147.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-07 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642776
• 关键词: Abdomen; Adenosine; Adult; Affect; Age; Asian; Asian population; Atherosclerosis; Biological; Blood; Body Weight; Body mass index; Cardiac; Cardiovascular system; Cell surface; Central obesity; Classification; Coronary; Development; Diabetes Mellitus; EFRAC; Echocardiography; Endothelium; Enzyme-Linked Immunosorbent Assay; Epidemiology; Ethnic Origin; Ethnic Population; Exercise; Fatty acid glycerol esters; Female; Glucose Intolerance; Goals; Heart Abnormalities; Heart Rate; Heart failure; Hepatic; High Prevalence; Hypertension; Immunologics; Individual; Inflammation; Insulin Resistance; Knowledge; Light; Link; Liver; Mass Spectrum Analysis; Measures; Mechanics; Mediating; Mediator; Metabolic; Metabolic dysfunction; Methods; Microvascular Dysfunction; Molecular; Morbidity - disease rate; Multi-Ethnic Study of Atherosclerosis; Muscle; Non obese; Obesity; Participant; Pathogenesis; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Physiological; Plasma; Population; Population Heterogeneity; Prediabetes syndrome; Prevalence; Process; Prognosis; Prospective cohort; Proteins; Proteomics; Protocols documentation; Risk Factors; Role; Sampling; South Asian; Stress; Stress Echocardiography; Subgroup; Symptoms; Testing; Viscera; Visceral fat; Weight; aptamer; arterial stiffness; cardiovascular disorder risk; cohort; diabetic; endothelial dysfunction; ethnic difference; experimental study; high risk; human old age (65+); hypertensive; improved outcome; lens; mortality; novel; novel therapeutics; preservation; prevent; proteomic signature; racial diversity; racial population; sex; single-cell RNA sequencing; tool

PROJECT SUMMARY The goal of this project is to fill gaps in our understanding of early heart failure stages and of heart failure with preserved ejection fraction (HFpEF). Over half of all heart failure patients have HFpEF, and are more likely to be older, diabetic, obese, hypertensive and have a prognosis that is equally poor as those with reduced ejection fraction. No treatment has been shown to improve outcomes in patients with HFpEF, highlighting an urgent need to understand the heterogeneous phenotypes and underlying biologic and physiologic mechanisms for HFpEF. We have established a prospective cohort of South Asians called the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study that is closely tied to the Multi-Ethnic Study of Atherosclerosis (MESA) for efficient cross-ethnic comparisons. We have found that South Asians have significantly higher prevalence of diabetes and metabolic abnormalities, even with normal body mass index, compared to the four MESA race/ethnic groups. Additionally, South Asians have very high levels of fat stored in ectopic depots (in the liver, muscle and around the abdominal viscera). This unique cohort with its distinct phenotype can be leveraged to understand the metabolic effects and mechanisms involved in heart failure. In this proposed study, we will use the thorough baseline and repeated metabolic characterization of MASALA study participants and will measure heart failure stages among 850 MASALA participants in a new Exam 3. We will characterize heart failure stages by symptoms, dynamic echocardiography, NTproBNP, and HFpEF will be confirmed by exercise stress echocardiography. We propose to 1) determine the epidemiology of heart failure among middle to older aged South Asians and compare heart failure stages and HFpEF prevalence in South Asians to the four MESA race/ethnic groups. We will determine whether differences in heart failure stages and HFpEF prevalence between South Asians and MESA groups are mediated by differences in dysglycemia, ectopic fat and other metabolic factors; 2) determine whether endothelial dysfunction, arterial stiffness, and coronary microvascular dysfunction drive HFpEF in South Asians, and if they mediate the association between dysglycemia, adiposity, and HFpEF; and 3) determine the blood-based proteomic signatures of heart failure and HFpEF among South Asians. We will identify, verify, and validate the proteomics profile of heart failure and HFpEF, and determine the immunologic signatures characterizing HFpEF. We expect that South Asians will have a high prevalence of HFpEF, and that we will better define the phenotype and underlying mechanisms for HFpEF relevant for metabolically unhealthy but normal weight populations.

项目摘要 该项目的目的是在我们对早期心力衰竭阶段的理解和心力衰竭的理解中填补空白 保留的射血分数（HFPEF）。超过一半的心力衰竭患者患有HFPEF，并且更有可能 年龄较大，糖尿病，肥胖，高血压，预后同样贫穷 射血分数。尚未证明没有治疗可以改善HFPEF患者的预后，从而突出显示 迫切需要了解异质表型以及潜在的生物学和生理学 HFPEF的机制。我们已经建立了一群名为“南亚人”的同伙 居住在美国的南亚人（MASALA）研究与多民族研究密切相关的动脉粥样硬化 动脉粥样硬化（MESA）进行有效的跨种族比较。我们发现南亚人有 糖尿病和代谢异常的患病率明显更高，即使体重指数正常， 与四个梅萨种族/族裔群体相比。此外，南亚人储存了很高的脂肪 在异位仓库中（在肝脏，肌肉和腹部内脏周围）。这个独特的队列，其独特 可以利用表型来了解心力衰竭涉及的代谢作用和机制。在 这项拟议的研究，我们将使用Masala的彻底基线和反复代谢表征 研究参与者，将在新考试中衡量850名Masala参与者中的心力衰竭阶段3。 将通过症状，动态超声心动图，NTPROBNP和HFPEF来表征心力衰竭阶段 通过运动压力超声心动图确认。我们建议1）确定心力衰竭的流行病学 在南亚年龄较大的南亚人中，比较了南方的心力衰竭阶段和HFPEF的患病率 亚洲人参加四个梅萨种族/族裔。我们将确定心力衰竭阶段的差异和 南亚人和梅萨组之间的HFPEF患病率是由血糖差异的差异介导的， 异位脂肪和其他代谢因素； 2）确定内皮功能障碍，动脉僵硬和 南亚人的冠状动脉微血管功能障碍驱动HFPEF，如果它们介导 血糖，肥胖和HFPEF； 3）确定心力衰竭的血液基蛋白质组学特征 和南亚人中的HFPEF。我们将识别，验证和验证心力衰竭的蛋白质组学概况 和HFPEF，并确定表征HFPEF的免疫学特征。我们希望南亚人 HFPEF的患病率很高，我们将更好地定义表型和基础 HFPEF的机制与代谢不健康但体重正常的人群有关。