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

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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.