Sleep and Circadian Mechanisms in Hypertension

Conditions studied

Hypertension, Cardiovascular Diseases, Cardiovascular Risk Factors, Circadian Rhythms, Sleep

About this study

This study is a mechanistic clinical trial designed to investigate the effects of the circadian system and sleep on non-dipping blood pressure (BP) in people with hypertension (HTN).

Interventions

• Other: At-home Polysomnography — Participants will complete one night of unattended polysomnography in their home environment (SOMNOtouch RESP, SOMNOmedics America Inc., FL, USA).
• Other: Circadian Protocol — Participants will spend 4 days/3 nights in the laboratory to uncover circadian rhythms. After 2 nights for acclimatization and baseline measurements, participants will stay awake for 28 hours in dim light, constant temperature, and semi-recumbent posture. Participants will be provided with standardized snacks regularly. Polysomnography, core body temperature, sleep, finger oximetry, electrocardiogram (ECG), and beat-to-beat BP will (except microneurography) be measured throughout. Blood will be drawn every 2-4h to analyze catecholamines, renin activity, and aldosterone. All other measurements, including BP, heart rate (HR), and flow-mediated dilation will be performed regularly. Salivary samples will be collected every 2hrs (when awake) to analyze melatonin levels. A recovery sleep period will be provided and baseline testing procedures will be performed. Investigators may acquire direct recordings of sympathetic activity using microneurography.
• Other: Rested Wakefulness Trial — Participants will start wearing an ambulatory BP monitor upon admission. Participants will be instrumented with full polysomnography (except leg myogram), and an intravenous catheter will be placed in the non-dominant arm. Participants will receive a standardized snack, and dinner \~4 hours before the start of the trial. Participants will be instrumented for microneurography. Participants will be awake in bed in dim light (\<8 lux). An investigator will constantly be present in the control room to monitor and ensure constant supine posture and wakefulness. Polysomnography, beat-by-beat BP, and neurogram for microneurography will be done throughout each trial into awakening; blood will be sampled before, during, and immediately after each trial (total of 8 samples in each trial). Flow-mediated dilation will be conducted before bed and after bed. The two trials will be conducted \~one month apart to accommodate the menstrual cycle phase in pre-menopausal females.
• Other: Overnight Sleep Trial — Participants will wear an ambulatory BP monitor upon admission. Participants will be instrumented with full polysomnography (except leg myogram), and an intravenous catheter will be placed in the non-dominant arm, and then participants will receive a standardized snack, and dinner 4 hours before the start of the trial. Polysomnography, beat-by-beat BP, and neurogram for microneurography will be done throughout each trial into awakening; blood will be sampled before, during, and immediately after each trial (total of 8 samples in each trial). Participants will be instrumented for microneurography. Participants will begin an 8-hour sleep opportunity (\<0.1 lux) at their chosen sleep time. At the end of the sleep episode, participants will be gently awoken in a standardized fashion by use of a mild auditory stimulus. Flow-mediated dilation will be conducted before bed and after sleep. The two trials will be conducted one month apart to accommodate the menstrual cycle.
• Behavioral: Regularized Sleep Schedule — All participants will be asked to maintain a self-selected bedtime (sleep duration not controlled) for two weeks as an intervention after the completion of the constant routine and both the resting wakefulness and overnight sleep trials. During this time, participants will be asked to call a time-stamped voicemail box upon waking and going to bed, as well as complete a daily sleep diary and wear an Actigraph device on their wrist. Ambulatory blood pressure will be measured at home before and at the end of the two-week intervention.

Primary outcomes

• Sleep duration (At-home Polysomnography) (1-2 nights)
• Sleep Episodes (At-home Polysomnography) (1-2 nights)
• Blood pressure (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)
• Heart rate (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)
• Heart rate variability (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)
• Epinephrine (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)
• Norepinephrine (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)
• Aldosterone (Circadian and Overnight sleep vs. rested wakefulness trial) (7 days)

Eligibility information

Study locations

• Oregon Health and Science University, Portland, Oregon 97239 United States