Project Summary Heart failure (HF) represents a modern epidemic. Hispanics are under-represented in HF clinical trials and epidemiologic studies. The few studies that have specifically examined Hispanics/Latinos in the US found that 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 [ES1]; R01 PI: Rodriguez) has found that compared to published estimates in non-Hispanic Whites, Hispanics have a high HF risk factor burden, worse diastolic function and higher LV stiffness. ECHO-SOL 2 (ES2) (PI: Rodriguez) obtained serial echo exams with preliminary data showing significant worsening of several echo parameters over an average of 4.5 years of follow-up. Mechanism(s) for the high susceptibility of Hispanics to HF and HF complications are incompletely understood and not well-accounted for by standard HF risk factors. Researchers have come to understand that vascular function contributes at both the early and advanced stages of HF pathogenesis. LV stroke volume depends on the important interaction of myocardial contractility with loading conditions from arterial system compliance.7 Ventricular-arterial stiffness has emerged as a powerful predictor of HF risk. There has been no study of comprehensive vascular assessment concurrent with a detailed echocardiographic exam. Thus, we propose to leverage the unique resources of ES1 and ES2 by characterizing vascular function in ECHO-SOL participants, examining key domains of vascular function phenotypes: (1) flow-mediated artery dilation (FMD) and reactive hyperemia; and (2) aortic pulse wave velocity (PWV) with pressure flow relations concurrently with a detailed third echocardiogram assessment [ECHO-SOL 3 (ES3)] 8-9 years post- baseline including 2D, color, spectral and tissue Doppler, strain and speckle tracking. Our goal is to determine how vascular function relates to cardiac abnormalities (including myocardial mechanics) and understand the ventricular-arterial relations in the development of cardiac dysfunction among Hispanics/Latinos, taking advantage of a rich database of clinical, sociocultural, and psychosocial risk factors from HCHS/SOL. Furthermore, we will also link datasets to leverage two NIH-funded cohorts with detailed vascular function data to address disparities among racial-ethnic minorities allowing us to compare vascular function in ES3 participants with non-Hispanic whites and blacks from the Framingham Heart Study and Jackson Heart Study. ES3 represents an innovative and cost-effective approach to advance our understanding of the links between vascular and myocardial function on HF progression. Our proposed study will provide the largest and most comprehensive dataset of vascular function parameters among Hispanics/Latinos in the US. In ES1 we found a high prevalence of diastolic dysfunction and LV stiffness, thus signaling Hispanics as a population at high risk for HF with preserved EF (HFpEF). Importantly, arterial–ventricular function has not been studied in Hispanics and may play an important role in predisposing this population to a higher risk for HFpEF. Assessment of vascular function can let us know who is at risk for developing clinical HFpEF. ES3 will facilitate the screening and identification of Hispanics who are at greatest HF risk, and can then be targeted for aggressive risk factor control to lower the burden of clinical HF in this vulnerable population.

Project Narrative This is the first ever study to comprehensively assess cardiac and vascular interaction / function / mechanics in a population-based cohort of Hispanics, incorporating novel serial STE-based analyses (LV strain and LV twist) to complement conventional assessment of LV systolic / diastolic function. The proposed research is highly relevant to public health because it offers the opportunity for comparative analysis of vascular structure / function / mechanics among African-Americans, Hispanic and Caucasians making this aspect of the project highly relevant to NIH's mission of Big Data to Knowledge research priority initiatives, as we will establish a potentially powerful dataset for future collaboration. In addition, the proposed research also represents a novel approach to understanding how patterns of progression of HF risk factors (from pre-DM to DM, pre-HTN to HTN or from normal BMI to obesity) relate to changes in cardiac phenotypes and potentially to clinical HF. Investigation into these very important areas will be extremely promising in learning about Hispanic cardiovascular health and highly relevant to future public health planning.