The Influence of Sleep on Cardiovascular Outcomes

Sleep is a fundamental determinant of heath; however, the impact of day-to-day variations in sleep patterns (i.e., sleep regularity) on cardiometabolic and vascular health has been underappreciated. Emerging evidence suggests that less regularity in sleep timing is correlated with cardiometabolic health and is a stronger predictor of mortality risk than sleep duration. In this cohort, the investigators will determine the influence of sleep regularity on mechanisms that impact cardiometabolic, vascular, and autonomic function.

The misalignment of behaviors (e.g., sleep) with the internal timing system (i.e., circadian misalignment) is likely a mechanistic contributor to unfavorable health outcomes. Laboratory experiments have shown that acute circadian misalignment increases markers of inflammation, alters metabolism, and elevates mean arterial pressure. We have shown that poorer overnight blood pressure dipping patterns are associated with circadian disruptions elicited by decreased sleep regularity, which occurs within 90-days of transitioning to a shift work schedule. There is a need to characterize the influence of sleep regularity on the underlying pathways that affect health.

The goal of this study is to determine the effect of an intervention targeting improved sleep regularity on circadian, metabolic, and vascular health markers. Participants within the lowest tertile for sleep regularity will adhere to a consistent sleep onset time (±30 min) for approximately 12-weeks. The outcomes that the investigators will focus on will be indices of hemodynamics (blood pressure, heart rate, autonomic function), blood biomarkers (markers of inflammation, oxidative stress, and triglycerides), energy metabolism, weight, and percent body fat. We will also have a sub-group of individuals with chronic pain to examine the effects of sleep regularity on pain outcomes.

1. Outpatient Biobehavioral Weeks: Actigraphy data will be collected across 2-weeks to assess habitual sleep patterns and calculate a sleep regularity index (SRI). 2. Biobehavioral Laboratory Visit: Participants will be asked to visit the OHSU School of Nursing (SON) Biobehavioral Laboratory space for two in-laboratory visits in dim-light settings, which will involve an evening stay (\~7.5h) to measure circadian markers, body composition, vascular function, and questionnaire data. Saliva samples will also be collected via salivettes in order to measure the hormone melatonin and determine each participants' dim-light melatonin onset (DLMO). Participants lowest SRI tertile (intervention group) will be instructed to maintain a consistent sleep onset time (±30 min self-selected sleep time) for up to 12-weeks. Compliance will be assessed across 6-weeks of outpatient bio-behavioral data collection via sleep logs, actigraphy, and daily surveys (described below). All other participants (control group) will be instructed to maintain their habitual sleep patterns for up to 12-weeks. 3. Ambulatory Monitoring: For participants in the intervention group, biobehavioral data collection will occur at Weeks 1-2, Weeks 6-7, and Weeks 11-12. For the control group, biobehavioral data collection will occur at Weeks 11-12. During these weeks, participants will wear an actigraphy device and keep sleep logs for 2-weeks during the biobehavioral data collection. Participants will also wear an ambulatory blood pressure cuff. Additionally, to measure glucose levels throughout the protocol, participants will be fitted with a continuous glucose monitor. Participants will complete daily surveys each bio-behavioral period to measure self-reported bed and wake times and naps. 4. Blood Biomarkers: At baseline and at Week 12, participants will visit the SON Biobehavioral Laboratory for a blood draw to obtain markers of inflammation, oxidative stress, and lipemic markers that will be measured with an \~10mL blood draw.

• Changes in MDA [Time frame: Week 0 and Week 12]
• Changes in TAC [Time frame: Week 0 and Week 12]
• Changes in CRP [Time frame: Week 0 and Week 12]
• Changes in triglycerides [Time frame: Week 0 and Week 12]
• Changes in percent body fat [Time frame: Week 0 and Week 12]
• Changes in weight [Time frame: Week 0 and Week 12]
• Changes in BMI [Time frame: Week 0 and Week 12]
• Changes in PIPR [Time frame: Week 0 and Week 12]
• Subjective Pain [Time frame: Week 0 and Week 12]