Understanding Racial Differences in Vascular Function and Ventricular-Vascular Coupling in Heart Failure with Preserved Ejection Fraction

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PROJECT ABSTRACT Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk for poor clinical outcomes including death and hospitalization, and there are no medical therapies that have definitively shown a reduction in the risk of death in this population. HFpEF involves multiple pathophysiological mechanisms, resulting in the heterogeneous phenotypes that are evident clinically, and which have potentially confounded previous HFpEF trials. Patients with HFpEF typically have comorbidities such as obesity, diabetes mellitus, and hypertension that are associated with endothelial dysfunction, increased oxidative stress (OS), and reduced nitric oxide (NO) bioavailability. Oxidative stress (OS) plays an important role in HF progression, as increasing OS disrupts NO signaling, inducing endothelial dysfunction and arterial stiffness that augment the workload for the failing heart. Importantly, Black patients develop HF at younger ages and are at higher risk for HF hospitalizations and death. Our prior data suggest that Blacks have higher levels of OS, lower NO bioavailability, and impaired vascular function as compared to Whites. Moreover, the higher prevalence of comorbidities like hypertension, obesity, and diabetes in Blacks compared to other race/ethnic groups further exacerbates these abnormalities, contributing to the earlier onset of HF and a more severe HF phenotype. Recent data suggest that Blacks display more adverse changes in ventricular structure and function in response to arterial stiffness. Although it is assumed the higher OS and lower NO observed in Blacks contributes to these changes, this has not been definitively shown in clinical studies. Our research proposal seeks to add to the pathophysiologic understanding of HFpEF by examining the association of biomarkers of NO and OS with noninvasive measurements of vascular function. Further, we will examine ventricular-arterial coupling in patients with HFpEF by describing the central pressure–flow relationship with noninvasive tools to allow for a comprehensive assessment of the arterial properties that contribute to ventricular afterload and abnormal ventricular-arterial coupling. Finally, we will specifically examine if there are racial differences in the measured biomarkers and assessments of ventricular-arterial coupling, to determine new targets for intervention that may help decrease racial disparities in heart failure severity and clinical outcomes.