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

项目摘要 主动脉僵硬随着年龄的增长而显著增加，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血流动力学耦合异常 靶器官损伤的发病机制，尤其是心衰。西班牙裔/拉丁裔人患心力衰竭的几率更高 与非西班牙裔白人和年轻的心衰患者相比，他们的并发症更多，左下角更低 心脏(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，与公布的非西班牙裔估计值相比 白人、西班牙裔有较高的心力衰竭危险因素负担，较差的舒张期功能和左心室僵硬，因此信号 保留EF的西班牙裔人发生HF的风险很高(HFpEF)。ECHO-SOL 2(ES2)(PI：Rodriguez)获得序列 平均随访4.3年，超声显示回声参数明显恶化。 标准的心力衰竭危险因素不能很好地解释西班牙裔人对心力衰竭易感性的机制(S)。 我们假设血管功能和室-动脉偶联对心衰有显著贡献。 西班牙裔美国人的发病机制和心力衰竭风险。因为心脏和血管系统是紧密相连的，LV卒中 容量取决于心肌收缩能力与来自动脉的负荷条件的重要相互作用 系统合规性。目前还没有关于综合血管功能和心脏功能的研究。 西班牙裔的动脉偶联评估伴随着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，利用心脏的纵向数据 表型以及临床、社会文化和心理社会风险因素，以综合表征 ES参与者的血管功能主要集中在主要的压力-血流表型：颈动脉-股动脉搏动 波速、中心脉压、特征阻抗和内皮功能 伴有详细的超声心动图评估的扩张/充血臂血流速度] 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。受损的 机械耦合导致右心和左心异常合并限制心输出量和 有助于B期心衰(现在称为前心衰)到症状性心衰，特别是肾功能衰竭。我们的目标是 全面描述拉美裔美国人的血管功能、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的关系 (包括心肌应变)，以检验主动脉僵硬损害机械耦合的假设。(目标2) 因为获得回声检查是我们主要关注的一个自然组成部分，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 每种轨迹的决定因素以及与血管等结局的独立关联 表型、总死亡率和心力衰竭。(目标3)最后，我们将把我们的数据集与NIH资助的其他队列联系起来 利用现有的血管功能数据对拉美裔/拉丁裔的血管功能进行汇集队列分析 分别来自弗雷明翰心脏研究和杰克逊心脏研究的非西班牙裔白人和黑人， 确定和解决少数族裔之间的血管差距。(目标4) 我们的大规模研究代表了一种创新和经济高效的方法(利用现有资源)来 促进我们对心力衰竭进展过程中的心室-血管相互作用的理解 和弱势群体。识别患有心力衰竭前和血管功能异常的拉美裔人可能有助于 区分哪些人是进展为心力衰竭的最高风险者，尤其是HFpEF。我们建议的研究 将提供最大的综合血管功能(压力-流量)参数数据集 在美国的拉美裔/拉丁裔中伴随的心脏测量。我们建议的研究将改善我们的 西班牙裔人心力衰竭发病机制和心力衰竭风险的概念框架，有助于筛查和 确定风险最高的人群，以降低这一脆弱人群的临床心力衰竭负担。

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.