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

基本信息

批准号：
10521911
负责人：
Carlos Jose Rodriguez
金额：
$ 136.81万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/10521911
关键词：
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 Echocardiography Endothelium 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 Lead 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 Race 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 base 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 psychosocial pulmonary arterial pressure racial and ethnic radial artery risk prediction model screening social culture sociodemographics unnecessary treatment vascular abnormality

项目摘要

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.

项目概要主动脉僵硬度随着年龄的增长而显着增加，并与高血压、心力衰竭 (HF) 和加速大脑老化。左心室和主动脉之间的异常血流动力学耦合导致靶器官损害的发病机制，特别是心力衰竭。西班牙裔/拉丁裔的心力衰竭发病率较高与非西班牙裔白人相比，心力衰竭患者更年轻，合并症更多，左下角也更高心室（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，与已发布的非西班牙裔估计值相比，白人、西班牙裔人的心力衰竭危险因素负担较高，舒张功能较差，左室僵硬度也较高，因此发出信号西班牙裔人患有 EF 保留的 HF (HFpEF) 的高风险。 ECHO-SOL 2 (ES2) (PI: Rodriguez) 获得序列号回声显示，在平均 4.3 年的随访中，回声参数显着恶化。标准心力衰竭风险因素无法很好地解释西班牙裔人心力衰竭的易感性机制。我们假设血管功能和心室-动脉耦合对心力衰竭有显着影响西班牙裔的发病机制和心力衰竭风险。由于心脏和脉管系统紧密相连，因此左心室中风容量取决于心肌收缩力与动脉负荷条件的重要相互作用系统合规性。目前尚无综合血管功能和心室功能的研究对西班牙裔患者进行动脉耦合评估并进行详细的超声心动图检查。因此，我们建议利用 HCHS/SOL、ES 和 ES2 的资源以及心脏方面的纵向数据表型分析以及临床、社会文化和心理社会风险因素，以全面表征 ES 参与者的血管功能重点关注关键的主要压力流表型：颈动脉-股动脉搏动波速、中心脉压、特征阻抗和内皮功能[血流介导扩张/充血的肱动脉血流速度]同时进行详细的超声心动图评估包括 2D、彩色、光谱/组织多普勒和散斑跟踪。我们的应用重点是血管功能障碍及其对心脏的相互作用/影响。受损机械耦合导致右心和左心异常的结合限制了心输出量和导致 B 期心力衰竭（现在称为心力衰竭前期）到症状性心力衰竭，特别是 HFpEF。我们的目标是全面描述西班牙裔/拉丁裔的血管功能压力-流量关系及其决定因素。（目标 1）然后，确定血管功能与心脏结构和功能异常之间的关系（包括心肌应变）来检验主动脉僵硬度损害机械耦合的假设。（目标2）因为进行超声检查是我们主要关注的自然组成部分，所以我们将受益于利用约 12 年的现有 ES 和 ES2 纵向数据来识别心脏轨迹，评估每个轨迹的决定因素以及与血管等结果的独立关联表型总体死亡率和心力衰竭。（目标 3）最后，我们将把我们的数据集与其他 NIH 资助的队列联系起来利用现有的血管功能数据对西班牙裔/拉丁裔的血管功能进行汇总队列分析分别与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一起，识别并解决少数种族之间的血管差异。（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（利用现有资源）的方法增进我们对代表性不足的心室血管相互作用对心力衰竭进展的理解和弱势群体。识别患有心衰前期和血管功能异常的西班牙裔人可能有助于区分那些进展为 HF（尤其是 HFpEF）风险最高的人群。我们提出的研究将提供最大的血管功能（压力-流量）参数综合数据集美国西班牙裔/拉丁裔的伴随心脏测量。我们提出的研究将改善我们的西班牙裔心力衰竭发病机制和心力衰竭风险的概念框架，有助于促进筛查和识别风险最大的人群，以减轻这一弱势群体的临床心力衰竭负担。