Project Details
Description
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.
Status | Finished |
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Effective start/end date | 9/1/22 → 8/31/23 |
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