Chrono-exercise is Medicine: Improving Blood Pressure and Vascular Function through Chronotherapy

项目总结/摘要 这项提案将确定运动时间疗法是否能改善老年人的夜间血压（BP） 高血压高血压是心血管疾病的主要可改变的危险因素， 高血压是美国人死亡的主要原因。据估计，高血压影响75%的老年人。尽管通常 使用药物和生活方式改变相结合的管理，估计只有21%的成年人 高血压患者的血压得到控制。因此，优化成人高血压患者的治疗方案是 至关重要夜间BP是BP管理中的一个新兴目标， 心血管疾病的后果。时间疗法与高血压药物联合使用可有效降低 夜间血压和未来的心血管风险，晚上服用的药物比 早上服用的药物初步证据表明，时间疗法与运动相结合（即， 计划的身体活动）可能影响对运动的急性和慢性反应。这项研究将 描述不同年龄和疾病的血管健康结果的昼夜节律，并指导运动时间 干预和结果评估，这将导致改善BP管理和血管功能。 三个具体目标将实现这一目标。目的1将综合评价年龄和 高血压对大血管和微血管昼夜节律的影响。微血管内皮功能 将通过48小时动态血压监测和体力活动，对功能和动脉硬度进行沿着评价 跟踪患有和不患有高血压的年轻人和老年人。目的2研究急性BP与血管性高血压的关系 对一天中不同时间进行的运动的反应，重点是运动后低血压， 尤其是夜间血压患有高血压的老年人将完成一个有氧运动和等长收缩训练 早上和晚上的手握练习。将评估基线和运动后BP反应 运动后立即和24小时使用动态血压监测。内皮功能和 还将在基线和运动后12小时评估微血管功能。目标3将决定 通过评估运动训练时间对夜间睡眠的影响， 绝经后妇女高血压患者的血压和血管功能。参与者将完成为期8周的 早晚有氧和等长握力训练。动态血压和血管 将在培训前和培训后对职能进行评估。总体假设是高血压是 其特征是血管功能的昼夜节律减少， 在降低血压和改善血管健康方面， 在一次运动回合和8周的运动训练后。这一建议将有助于在 高血压的治疗包括在运动建议中的时间疗法，优化治疗 高血压的选择，这反过来又会改善老年人的健康。

PROJECT SUMMARY/ABSTRACT This proposal will determine if exercise chronotherapy improves nocturnal blood pressure (BP) in older adults with hypertension. Hypertension is the leading modifiable risk factor for cardiovascular disease, which is the leading cause of death in the U.S. Hypertension is estimated to affect 75% of older adults. While typically managed using a combination of medications and lifestyle modifications, it is estimated that only 21% of adults with hypertension have controlled BP. Therefore, optimizing treatment options for adults with hypertension is of paramount importance. Nocturnal BP is an emerging target in the management of BP, given its association with cardiovascular outcomes. Chronotherapy combined with hypertension medications is effective at lowering nocturnal BP and future cardiovascular risk, with medications taken in the evening being more effective than medications taken in the morning. Preliminary evidence suggests chronotherapy combined with exercise (i.e., planned physical activity) may impact the acute and chronic responses to exercise. This research will characterize diurnal rhythms of vascular health outcomes across age and disease and guide timing of exercise intervention and outcome assessment, which will lead to improved BP management and vascular function. Three specific aims will accomplish this goal. Aim 1 will comprehensively evaluate the effect of age and hypertension on macrovascular and microvascular diurnal rhythms. Endothelial function, microvascular function and arterial stiffness will be evaluated along with 48-hr ambulatory BP monitoring and physical activity tracking in young and older adults with and without hypertension. Aim 2 will study the acute BP and vascular responses to exercise performed at different times of the day, focusing on post-exercise hypotension, in particular nocturnal BP. Older adults with hypertension will complete a session of aerobic and isometric handgrip exercise in the morning and evening. Baseline and post-exercise BP responses will be evaluated immediately following exercise and for 24-hr using ambulatory BP monitoring. Endothelial function and microvascular function will also be assessed at baseline and 12-hr post-exercise. Aim 3 will determine the long-term impacts of exercise chronotherapy by evaluating exercise training time of day effects on nocturnal BP and vascular function in postmenopausal women with hypertension. Participants will complete 8 weeks of aerobic and isometric handgrip exercise training in the morning and evening. Ambulatory BP and vascular function will be assessed pre- and post-training. The overarching hypothesis is that hypertension is characterized by the reduction of diurnal rhythms in vascular function and that evening exercise in this population will be more effective than morning exercise at lowering BP and improving vascular health both after a single exercise bout and 8 weeks of exercise training. This proposal will facilitate a paradigm shift in the treatment of hypertension to include chronotherapy in the exercise recommendations, optimizing treatment options for hypertension which in turn will improve the health of older adults.