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

项目摘要： 射血分数(HFpEF)保留的心力衰竭(HF)在老年人中很常见，并在 流行率。此外，在高频的负担方面存在很大的种族差异，包括HFpEF，如 非裔美国人(AA)的心力衰竭患病率比其他种族高得多。在一系列流行病学调查中 研究表明，低心肺适合度(CRF)，以最大摄氧量衡量 (最大负荷试验中的VO2峰值)是心力衰竭风险较高的独立预测指标，尤其是 HFpEF，在老年人中。再者，再生障碍性贫血患者的促肾上腺皮质激素释放激素水平始终低于其他 比赛。总而言之，低CRF和CRF随年龄增长而加速下降可能是导致 心力衰竭负担的种族差异。更好地理解种族问题背后的机制 低CRF患病率和年龄相关性CRF下降之间的差异是开发新的、有效的关键 预防老年再生障碍性贫血患者心衰的方法。因此，在这项研究中，我们旨在评估种族 慢性肾功能衰竭年龄相关性下降的差异及其潜在的生物学机制。为此，我们将 在达拉斯心脏研究(DHS)内进行嵌套病例对照研究，DHS是一个多种族的社区队列- 居住的个人，包括老年AA和白人成年人，在年龄、性别和风险因素(BMI、收缩压)方面匹配 血压，糖尿病状况)在中年(平均年龄50-55岁)接受CRF测试 国土安全部第二阶段访问(2007-09)，并将在10年后(2019-2022)参加国土安全部第三阶段。参与者 将进行重复的CRF评估和全面的最先进的表型鉴定，以全面 评估慢性肾功能衰竭的种族差异的潜在机制，包括：每搏量储备 超声心动图、心率储备、心肌灌注、心脏MRI心肌能量学、骨骼 肌肉能量学检测采用7T磁共振成像，局部脂肪组织检测采用全身磁共振成像。峰值VO2 结合其中枢和外周决定因素将在匹配的AA和白色之间进行比较 DHS第三阶段的参与者。成功完成这两个目标将量化再生障碍性贫血患者CRF的下降 首次与白人老年人进行比较，并阐明了具体的机制，从而提供了关键的 深入了解低CRF的潜在病理生理机制。

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.