Sleep, Hypertension, and Nocturia: a Multicomponent Approach for Comorbid Illnesses

The investigators posit that a vicious cycle operates between nocturia, poor sleep, and nighttime hypertension (HTN). HTN act through the pressure-natriuresis mechanism that links sodium (Na) and BP homeostasis: periodic increases in BP drive compensatory renal excretion of Na (natriuresis) and water (diuresis) to reduce blood volume and BP. Normally, BP and natriuresis declines during sleep, decreasing nighttime urine volume (NUV). Elevated nighttime BP increases nocturnal natriuresis causing an increase in nighttime urine volume and hence, NP: the major etiologic factor for nocturia in the elderly. In a recently completed study (AG050892, PI:Tyagi), it was found that poor sleep blunts the normal nighttime rise in antidiuretic hormone-a potent Na conserving hormone, which leads to nocturnal natriuresis and, as a result, NP. Hence, our model incorporates the effects of poor sleep and nighttime HTN on natriuresis, NP, and nocturia. The investigators postulate that treatments targeted towards these etiologies will help break this vicious cycle. Traditionally, antihypertensive medications are dosed in the morning targeting daytime BP. However, some research suggests that nighttime BP best predicts risk for major cardiovascular events. Several clinical trials of bedtime dosing of BP medication-chronotherapy- show better nighttime BP control. However, no clinical studies have considered or tested chronotherapy as a treatment for nocturia. With respect to poor sleep, the investigators have shown that brief behavioral treatment of insomnia (BBTI) significantly improves not only sleep but also self-reported nocturia among the elderly. Therefore, the investigators envision a multicomponent approach with chronotherapy (bedtime dosing of certain antihypertensives) and behavioral sleep intervention (BBTI) to concurrently address the prevalent and chronic, mutually exacerbating conditions: nocturia, poor sleep, and HTN. The current proposal aims to collect pilot data for a definitive randomized clinical trial. In the proposed pilot study 30 community-dwelling older adults (aged \>65) who take at ≥1 daily non-diuretic antihypertensive medication, have a mean SBP \>135 mm Hg, and awaken ≥2 times nightly to void will be randomly assigned to one of the 3 groups of 10 participants each to 1) morning (am) HTN medication dosing, 2) BBTI with am HTN medication dosing, 3) nighttime non-diuretic HTN medication dosing (chronotherapy) for 6 weeks. At baseline and 6 weeks, participants will undergo 48-hour ambulatory BP monitoring, in-home sleep study, complete a 3-day bladder diary. This protocol will allow the investigators to accomplish following Aims: Aim1: To assess the feasibility and effect of chronotherapy and BBTI in older adults with multiple comorbidities: HTN and nocturia Hypothesis 1: Chronotherapy and BBTI will be (a) feasible treatment options among comorbid older adults, and (b) nocturia and nighttime urine volume, and (c) nighttime systolic blood pressure (SBP) will have a greater decrease in BBTI and chronotherapy groups than usual care. Aim 2: Assess safety and treatment compliance with chronotherapy. Hypothesis 2: The investigators will assess treatment compliance and also collect data on nocturnal lightheadedness and falls to begin to address the safety of HTN chronotherapy.