Evaluation of Racial Differences in Cardiorespiratory Fitness Decline with Aging & Underlying Biological Mechanisms

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Project Abstract: Heart failure (HF) with preserved ejection fraction (HFpEF) is common in older adults and increasing in prevalence. Furthermore, there are substantial racial disparities in the burden of HF, including HFpEF, such that African American (AA) have much higher prevalence of HF than other races. In a series of epidemiological studies, we have demonstrated that low cardiorespiratory fitness (CRF), measured as peak oxygen uptake (peak VO2) on a maximal stress test, is a strong independent predictor of higher risk of HF, particularly HFpEF, in older adults. Furthermore, CRF levels among AA are consistently lower as compared with other races. Taken together, low CRF and accelerated age-related decline in CRF may be key contributors to the racial differences in the burden of HF. A better understanding of the mechanisms underlying the racial disparities in prevalence of low CRF and age-related CRF decline is key to developing novel, effective approaches to prevention of HF in older AA adults. Accordingly, in this study, we aim to evaluate the racial differences in age-related decline in CRF and their underlying biological mechanisms. To this end, we will perform a nested case-control study within the Dallas Heart Study (DHS), a multi-ethnic cohort of community- dwelling individuals, including older AA and white adults matched for age, sex, and risk factors (BMI, systolic blood pressure, diabetes status) who underwent CRF testing in middle-age (mean age 50-55) as part of the DHS phase 2 visit (2007-09) and are participating in the DHS phase 3 10-years later (2019-2022). Participants will undergo repeat CRF assessment and comprehensive state-of-the-art phenotyping to comprehensively evaluate the potential mechanisms of racial differences in CRF, including the following: stroke volume reserve by echocardiogram, heart rate reserve, myocardial perfusion, myocardial energetics by cardiac MRI, skeletal muscle energetics assessment by 7T MRI, and regional adipose tissue by whole body MRI. Peak VO2 combined with its central and peripheral determinants will be compared among matched AA and white participants in the DHS phase 3. Successful completion of these two aims will quantify the CRF decline in AA versus white older individuals for the first time and elucidate specific mechanisms, thereby, providing critical insight into the underlying pathophysiologic mechanisms of low CRF.