Vascular Determinants of Stage B HF among Hispanics: the role of the Heart-Vascular Interaction

西班牙裔 B 期心力衰竭的血管决定因素：心脏与血管相互作用的作用

• 批准号: 10686910
• 负责人: Carlos Jose Rodriguez
• 金额: $ 124.37万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686910
• 关键词: Acceleration; Acculturation; Address; Adverse event; Affect; African American; African American population; Age; Ancillary Study; Aorta; Area; Big Data to Knowledge; Black Populations; Blood Vessels; Cardiac; Cardiac Output; Cardiovascular system; Carotid Arteries; Caucasians; Characteristics; Clinical; Clinical Trials; Cohort Analysis; Collaborations; Color; Communities; Complement; Coupled; Coupling; Data; Data Set; Development; Diabetes Mellitus; Dilatation - action; Disparity; Early identification; Echocardiography; Endothelium; Femur; Framingham Heart Study; Functional disorder; Funding; Future; Goals; Health; Health Planning; Heart; Heart Abnormalities; Heart failure; Hispanic; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Hypertension; Impairment; Incidence; Infrastructure; Intervention; Investigation; Jackson Heart Study; Latino Population; Learning; Left; Left Ventricular Ejection Fraction; Left Ventricular Mass; Left atrial structure; Left ventricular structure; Link; Measurement; Measures; Mechanics; Mediating; Memory impairment; Mission; Monitor; Myocardial; Myocardial dysfunction; National Heart, Lung, and Blood Institute; Not Hispanic or Latino; Obesity; Organ; Outcome; Parents; Participant; Pathogenesis; Patient Care; Patients; Pattern; Persons; Phenotype; Physiologic pulse; Population; Predisposition; Prevalence; Public Health; Publishing; Pulse Pressure; Pump; Relaxation; Research; Research Priority; Resistance; Resources; Right ventricular structure; Risk; Risk Factors; Role; Signal Transduction; Social Discrimination; Social isolation; Socioeconomic Status; Statistical Methods; Stroke Volume; Structure; Study of Latinos; System; Testing; Tissues; Underrepresented Populations; United States; United States National Institutes of Health; Vascular Diseases; Vascular System; Ventricular; Vulnerable Populations; Work; aging brain; biracial; brachial artery; cardiovascular health; clinical risk; cohort; comorbidity; cost effective; data repository; design; electric impedance; ethnic difference; ethnic minority; femoral artery; follow-up; health disparity; heart imaging; hemodynamics; high risk; improved; innovation; insight; middle age; mortality; next generation; novel strategies; population based; preservation; pressure; prevent; progression risk; psychosocial; pulmonary arterial pressure; racial difference; racial minority; radial artery; risk prediction model; screening; social culture; sociodemographics; unnecessary treatment; vascular abnormality

Project Summary Aortic stiffness increases markedly with age and is associated with hypertension, heart failure (HF) and accelerated brain aging. Abnormal hemodynamic coupling between left ventricle and aorta contributes to pathogenesis of target organ damage, particularly HF. Hispanics/Latinos have a higher incidence of HF compared to non-Hispanic Whites and present younger with HF with more co-morbidities and a lower left ventricular (LV) ejection fraction. Furthermore, the community-based Echocardiographic Study of Latinos (ECHO-SOL [ES]; R01 PI: Rodriguez) has found that compared to published estimates in non-Hispanic Whites, Hispanics have a higher HF risk factor burden, worse diastolic function and LV stiffness thus signaling Hispanics at high risk for HF with preserved EF (HFpEF). ECHO-SOL 2 (ES2) (PI: Rodriguez) obtained serial echos showing significantly worsening of echo parameters over an average of 4.3 years of follow-up. Mechanism(s) for the susceptibility of Hispanics to HF are not well-accounted for by standard HF risk factors. We hypothesize that vascular function and ventricular-arterial coupling significantly contributes to HF pathogenesis and HF risk in Hispanics. Because the heart and vasculature are intimately coupled, LV stroke volume depends on the important interaction of myocardial contractility with loading conditions from arterial system compliance. There has been no study of comprehensive vascular function and ventricular- arterial coupling assessment concomitant with a detailed echocardiographic exam in Hispanics. Thus, we propose leveraging the resources of HCHS/SOL, ES and ES2 with longitudinal data on cardiac phenotyping as well as clinical, sociocultural, and psychosocial risk factors to comprehensively characterize vascular function in ES participants focusing on key primary pressure-flow phenotypes: carotid-femoral pulse wave velocity, central pulse pressure, characteristic impedance and endothelial function [flow mediated dilatation / hyperemic brachial flow velocities] concomitant with a detailed echocardiographic assessment including 2D, color, spectral / tissue Doppler and speckle tracking. Our application is focused on vascular dysfunction and its interaction / effects on the heart. Impaired mechanical coupling contributes to combination of right and left heart abnormalities limits cardiac output and contributes to the stage B HF (now termed pre-HF) to symptomatic HF, particularly HFpEF. Our goal is to comprehensively describe vascular function pressure-flow relations and its determinants in Hispanics/Latinos. (Aim 1) Then, determine how vascular function relates to cardiac structural and functional abnormalities (including myocardial strain) to test the hypothesis that aortic stiffness impairs mechanical coupling. (Aim 2) Because obtaining an echo exam is a natural component of our primary focus, we will have the benefit of leveraging ~12 years of existing ES and ES2 longitudinal data to identify cardiac trajectories, assess the determinants of each trajectories and the independent association with outcomes such as vascular phenotypes overall mortality and HF. (Aim 3) Lastly, we will link our dataset with other NIH-funded cohorts with existing vascular function data to perform pooled cohort analyses of vascular function of Hispanics/Latinos with non-Hispanic whites and blacks from the Framingham Heart Study and Jackson Heart Study respectively, to identify and address vascular disparities among racial-ethnic minorities. (Aim 4) Our large-scale study represents an innovative and cost-effective (leveraging existing resources) approach to advancing our understanding of the ventricular-vascular interaction on HF progression in an underrepresented and vulnerable population. Identification of Hispanics with pre-HF and abnormal vascular function may help to differentiate those who are at the highest risk for progression to HF, particularly HFpEF. Our proposed study will provide the largest comprehensive dataset of vascular function (pressure-flow) parameters with concomitant cardiac measures among Hispanics/Latinos in the US. Our proposed study will improve our conceptual framework of HF pathogenesis and HF risk in Hispanics and serve to facilitate the screening and identification of those at greatest risk, to lower the burden of clinical HF in this vulnerable population.

项目摘要 主动脉僵硬随着年龄的增长明显增加，与高血压，心力衰竭（HF）和 加速大脑衰老。左心室和主动脉之间的异常血流动力耦合有助于 目标器官损伤的发病机理，尤其是HF。西班牙裔/拉丁美洲人的HF发生率更高 与非西班牙裔白人相比，并具有更年轻的HF，并具有更多的合并症和左下 心室（LV）射血分数。此外，基于社区的拉丁裔超声心动图研究 （Echo-sol [es]; R01 PI：Rodriguez）发现，与非西班牙裔的已发表估计值相比 白人，西班牙裔的HF风险因素负担更高，舒张功能较差和LV刚度，因此发出信号 HF保存的EF（HFPEF）的高风险西班牙裔风险。 Echo-Sol 2（ES2）（PI：Rodriguez）获得了串行 回声显示回声参数在平均4。3年的随访中显着恶化。 对于标准的HF危险因素而言，西班牙裔对HF的敏感性的机制并未得到很好的评估。 我们假设血管功能和心室 - 动脉耦合显着有助于HF 西班牙裔的发病机理和HF风险。因为心脏和脉管系统密切相关，所以LV中风 体积取决于心肌收缩性与动脉的负载条件的重要相互作用 系统合规性。没有研究全面的血管功能和心室 - 动脉耦合评估与西班牙裔有关的详细超声心动图检查。因此， 我们建议使用心脏的纵向数据利用HCHS/SOL，ES和ES2的资源 表型以及临床，社会文化和社会心理风险因素全面表征 ES参与者的血管功能，重点是主要的主要压力流表型：颈动脉脉搏 波速，中央脉压，特征阻抗和内皮功能[流动介导 扩张 /高血压流速度]与详细的超声心动图评估有关 包括2D，颜色，光谱 /组织多普勒和斑点跟踪。 我们的应用集中在血管功能障碍及其对心脏的相互作用 /影响上。受损 机械耦合有助于左右心脏异常的组合限制心脏输出和 有助于BHF期（现称为HF），尤其是HFPEF。我们的目标是 全面描述了西班牙裔/拉丁裔的血管功能压力流关系及其决定因素。 （目标1）然后，确定血管功能与心脏结构和功能异常的关系 （包括心肌菌株），以测试主动脉刚度会损害机械耦合的假设。 （目标2） 因为参加回声考试是我们主要重点的自然组成部分，所以我们将受益 利用约12年的现有ES和ES2纵向数据识别心脏轨迹，评估 每个轨迹的决定因素和与血管等结果的独立关联 表型总体死亡率和HF。 （AIM 3）最后，我们将将数据集与其他NIH资助的队列联系起来 使用现有的血管功能数据，以执行西班牙裔/拉丁裔血管功能的汇总队列分析 分别来自弗雷明汉心脏研究和杰克逊心脏研究的非西班牙裔白人和黑人 识别和解决种族少数民族之间的血管差异。 （目标4） 我们的大规模研究代表了一种创新且具有成本效益的（利用现有资源）的方法 促进我们对人为不足的HF进展的心室血管相互作用的理解 和脆弱的人口。具有前HF和异常血管功能的西班牙裔鉴定可能有助于 区分那些面向HF的风险最高的人，尤其是HFPEF。我们提出的研究 将提供最大的血管功能（压力流）参数的综合数据集 美国西班牙裔/拉丁美洲人的心脏措施。我们提出的研究将改善我们的 西班牙裔HF发病机理和HF风险的概念框架，并有助于筛查和 确定那些处于最大风险的人，以降低该脆弱人群的临床HF负担。