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

项目摘要 心力衰竭和射血分数保留（HFpEF）患者的临床结局较差的风险较高 包括死亡和住院治疗，并且没有任何医学治疗明确显示减少 死亡的风险。HFpEF涉及多种病理生理机制，导致 临床上明显的异质性表型，可能混淆既往HFpEF 审判HFpEF患者通常伴有肥胖、糖尿病和高血压等合并症 与内皮功能障碍、氧化应激（OS）增加和一氧化氮（NO）减少相关 生物利用度氧化应激（OS）在HF进展中起重要作用，因为OS增加会破坏NO 信号传导，诱导内皮功能障碍和动脉僵硬，增加衰竭心脏的工作负荷。 重要的是，黑人患者发生HF的年龄较轻，HF住院的风险较高， 死亡我们先前的数据表明，黑人有较高水平的OS，较低的NO生物利用度， 与白人相比的血管功能。此外，高血压等合并症的患病率越高， 与其他种族/民族相比，黑人的肥胖和糖尿病进一步加剧了这些异常， 导致HF的早期发作和更严重的HF表型。最近的数据显示， 显示心室结构和功能对动脉僵硬度的反应更不利。虽然 假设在黑人中观察到的更高的OS和更低的NO有助于这些变化，这还没有被证实。 在临床研究中明确显示。我们的研究计划旨在增加病理生理学 通过检查NO和OS生物标志物与无创性HFpEF的相关性， 测量血管功能。此外，我们还将研究室-动脉耦合在患者 通过无创工具描述中心压力-流量关系， 综合评估导致心室后负荷和异常的动脉特性 心室-动脉耦合最后，我们将具体检查是否有种族差异的测量 心室-动脉耦合的生物标志物和评估，以确定新的干预靶点， 有助于减少心力衰竭严重程度和临床结果的种族差异。

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.