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

项目概要/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和老年男性和女性。目的2研究急性BP 以及血管对一天中不同时间进行的运动的反应，重点是夜间BP， 运动性低血压和晨起血管功能。患有高血压的老年男性和女性将完成 在上午和下午/晚上进行有氧和等长握柄练习。英国石油公司将 运动后立即进行评估，并使用动态血压监测持续24小时。内皮和 还将在每次运动后的早晨评估微血管功能。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。参与者将完成两个为期6周的 早晚各一次有氧和等长握力训练 下午/晚上。将在训练前后评估动态血压和血管功能，并进行比较 一天中的某个时间。总体假设是，高血压的特征是降低 昼夜节律的血管功能和晚间锻炼，在这一人群将更有效地比 晨练降低血压和改善血管健康后，单次运动回合和6周 运动训练。该提案有能力优化高血压的治疗选择，包括 时间疗法在运动的建议，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 males and females 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 nocturnal BP, post- exercise hypotension, and morning vascular function. Older males and females with hypertension will complete a session of aerobic and isometric handgrip exercise in the morning and late afternoon/evening. BP will be evaluated immediately following exercise and for 24-hr using ambulatory BP monitoring. Endothelial and microvascular function will also be evaluated the morning after each exercise bout. 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 two 6-week periods of aerobic and isometric handgrip exercise training with one period in the morning and one in the late afternoon/evening. Ambulatory BP and vascular function will be assessed pre- and post-training and compared between time of day. 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 6 weeks of exercise training. This proposal has the capacity to optimize treatment options for hypertension by including chronotherapy in the exercise recommendations, which in turn will improve the health of older adults.