BACKGROUND: In people with obstructive sleep apnea (OSA), adverse cardiovascular events, such as myocardial infarction, occur more commonly in the middle of the night than at other times of the day. These events could occur as a result of the nighttime physiological changes in OSA, but the endogenous circadian system has been implicated in increased cardiovascular risk in OSA. Vascular endothelial function is a marker of prospective cardiovascular risk and is impaired in OSA. We hypothesized that the nighttime risk in OSA could be due to a circadian system-driven nighttime impairment in vascular endothelial function.
METHODS: Twelve adults (healthy except for untreated moderate to severe OSA, 8 men and 4 women, 51± SD 7 years; apnea/hypopnea index, 29±19 hours of sleep) completed a 5-day circadian protocol consisting of 10 recurring 5-hour 20-minute periods (2 hours 40 minutes each of wake periods and sleep opportunities) to separate the circadian system's effects from those of behaviors such as exercise, meal intake, and sleep. We measured flow-mediated dilation of the brachial artery during each wake period in each participant.
RESULTS: We discovered a significant circadian rhythm in flow-mediated dilation (=0.019), and flow-mediated dilation normalized to shear rate (=0.037) with a trough at the circadian phase corresponding to ≈3:00 am with a peak-to-trough change of 2.5 percentage points, or 82%. There was no significant circadian rhythm in the baseline diameter (=0.39). P P P
CONCLUSIONS: These data suggest that the circadian system impairs vascular endothelial function during the biological night, potentially increasing vascular vulnerability in people with untreated OSA.
REGISTRATION: URL: https://clinicaltrials.gov/; Unique Identifier: NCT02202811.
Circadian Biology