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

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.