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

项目摘要/摘要 这项提案将确定运动计时疗法是否能改善老年人的夜间血压。 患有高血压。高血压是心血管疾病的主要可改变的危险因素，这是 高血压是美国主要的死因。据估计，75%的老年人会受到高血压的影响。虽然通常 通过药物治疗和改变生活方式相结合的方式进行管理，估计只有21%的成年人 高血压患者的血压得到了控制。因此，优化成人高血压患者的治疗方案是 最重要的是。夜间BP是BP管理中的一个新兴目标，因为它与 对心血管结果的影响。时辰疗法与高血压药物联合治疗对降低血压有效 夜间血压和未来心血管风险，晚上服药比晚上服药更有效 早上吃的药。初步证据表明，时间疗法与运动相结合(即， 有计划的体力活动)可能会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，并指导锻炼的时机 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。目标1将综合评估年龄和 高血压对大血管和微血管昼夜节律的影响。内皮功能，微血管 功能和动脉僵硬将与48小时动态血压监测和体力活动一起进行评估 对患有和不患有高血压的年轻人和老年人进行跟踪。目的2将研究急性血压和血管 在一天中的不同时间对运动的反应，重点是运动后低血压，在 特别是夜间活动的BP。患有高血压的老年人将完成有氧和等长距离训练 早晚进行握力练习。将评估基线和运动后的BP反应 运动结束后立即进行24小时动态血压监测。内皮功能和 微血管功能也将在基线和运动后12小时进行评估。目标3将决定 运动计时疗法对夜间运动训练时间效应的远期影响 绝经后女性高血压患者的血压和血管功能。参与者将完成为期8周的 早晚进行有氧和等长握力练习。动态血压和血管 将在培训前和培训后对功能进行评估。最重要的假设是高血压是 以血管功能的昼夜节律减少和晚间锻炼为特征 在降低血压和改善血管健康方面，人群将比晨练更有效 经过一次单次运动和8周的运动训练。这一提议将促进 高血压的治疗应将时间疗法纳入运动建议，优化治疗 高血压的选择，这反过来将改善老年人的健康。

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.