Metabolic effects and mechanisms for heart failure in South Asians

项目总结 这个项目的目标是填补我们对早期心力衰竭阶段和心力衰竭的理解的空白 保留射血分数(HFpEF)。超过一半的心力衰竭患者患有HFpEF，而且更有可能 年龄较大，糖尿病，肥胖，高血压，预后与减退的人一样差 射血分数。目前还没有证据表明治疗可以改善HFpEF患者的预后，这突显了一种 迫切需要了解不同的表型和潜在的生物和生理 HFpEF的机制。我们已经建立了一个潜在的南亚人队列，称为 与多种族研究密切相关的南亚人在美国生活的动脉粥样硬化(MASLA)研究 用于有效的跨种族比较的动脉粥样硬化(MESA)。我们发现南亚人有 即使在体重指数正常的情况下，糖尿病和代谢异常的患病率也要高得多， 与四个台地种族/民族相比。此外，南亚人储存的脂肪水平非常高 在异位仓库中(在肝脏、肌肉和腹部内脏周围)。这一独特的群体具有其独特的 表型可以用来了解心力衰竭的代谢效应和机制。在……里面 在这项拟议的研究中，我们将使用马萨拉的彻底基线和重复代谢特性 研究参与者将在一项新的考试3中测量850名Masala参与者的心力衰竭阶段。 将通过症状、动态超声心动图、NTproBNP和HFpEF来表征心力衰竭阶段 经运动负荷超声心动图证实。我们建议1)确定心力衰竭的流行病学 在中老年南亚人中进行比较，并比较南方心力衰竭分期和HFpEF患病率 四个梅萨种族/民族的亚洲人。我们将确定心力衰竭阶段和 南亚人和梅萨人之间的HFpEF患病率是由血糖异常的差异所调节的， 异位脂肪和其他代谢因子；2)决定内皮功能障碍、动脉僵硬和 南亚人冠状动脉微血管功能障碍导致HFpEF，如果它们介导两者之间的关联 血糖异常、肥胖和HFpEF；3)决定心力衰竭的血液蛋白质组学特征 以及南亚人中的HFpEF。我们将识别、验证和验证心力衰竭的蛋白质组学特征 和HFpEF，并确定HFpEF的免疫学特征。我们预计南亚人 会有很高的HFpEF患病率，我们将更好地定义表型和潜在的 HFpEF的机制与代谢不健康但体重正常的人群有关。

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.