Effects of obstructive sleep apnea on endogenous circadian rhythms assessed during relaxed wakefulness; an exploratory analysis

ABSTRACT

Obstructive sleep apnea (OSA) is associated with hypertension, cardiovascular disease, and a change in the 24 h pattern of adverse cardiovascular events and mortality. Adverse cardiovascular events occur more frequently in the middle of the night in people with OSA, earlier than the morning prevalence of these events in the general population. It is unknown if these changes are associated with a change in the underlying circadian rhythms, independent of behaviors such as sleep, physical activity, and meal intake. In this exploratory analysis, we studied the endogenous circadian rhythms of blood pressure, heart rate, melatonin and cortisol in 11 participants (48 ± 4 years; seven with OSA) throughout a 5 day study that was originally designed to examine circadian characteristics of obstructive apnea events. After a baseline night, participants completed 10 recurring 5 h 20 min behavioral cycles divided evenly into standardized sleep and wake periods. Blood pressure and heart rate were recorded in a relaxed semirecumbent posture 15 minutes after each scheduled wake time. Salivary melatonin and cortisol concentrations were measured at 1–1.5 h intervals during wakefulness. Mixed-model cosinor analyses were performed to determine the rhythmicity of all variables with respect to external time and separately to circadian phases (aligned to the dim light melatonin onset, DLMO). The circadian rhythm of blood pressure peaked much later in OSA compared to control participants (group × circadian phase, p < .05); there was also a trend toward a slightly delayed cortisol rhythm in the OSA group. Rhythms of heart rate and melatonin did not differ between the groups. In this exploratory analysis, OSA appears to be associated with a phase change (relative to DLMO) in the endogenous circadian rhythm of blood pressure during relaxed wakefulness, independent of common daily behaviors.

KEYWORDS:

• Sleep disordered breathing
• circadian rhythms
• circadian clock
• blood pressure
• adverse cardiovascular events
• non-dipping blood pressure

Acknowledgments

We thank the Center for Clinical Investigation staff for expert assistance, and the Harvard Catalyst Clinical and Translational Science Center for support.

Author contributions

MPB, HW, and SAS designed the study; MPB, KH, FAJLS, CS, HW, MVH, MM, and SAS collected data; MPB, SST, KH, FAJLS, PND, and SAS analyzed data; MPB, SST, and SAS drafted manuscript; MPB, SST, and SAS revised manuscript.

Declaration of interests

The authors report no conflicts of interest.

Notes

¹ In this paper, we differentiate daily rhythms of physiological variables (those measures that are rhythmic when measured across a normal 24 hour period with typical daily patterns of eating, waking, and nightly sleep) from endogenous circadian rhythms (those measures that are rhythmic in the absence of external time cues and driven by the internal circadian system). Assuming a simple additive model, the measured daily pattern in a variable such as blood pressure would be the sum of the basal circadian rhythm in blood pressure plus the effects on blood pressure of the daily responses to environmental and behavioral changes.

Additional information

Funding

This work was funded by an American Sleep Medicine Foundation Focused Project Award, T32-HL007901, and R21-HL140377 (MPB); R21-HL092407 and R01-HL125893 (SAS); F32-HL131308, KL2TR002370, and National Space Biomedical Research Institute through NCC 9-58 (SST); 1UL1-RR025758 and 8UL1-TR000170 to the Harvard Catalyst Clinical and Translational Science Center; and by the Oregon Institute of Occupational Health Sciences at Oregon Health & Science University via funds from the Division of Consumer and Business Services of the State of Oregon (ORS 656.630).