Influence of circadian alignment and sleep timing variability on sex-specific inflammatory markers in healthy adults

Sleep and circadian disruption affect inflammatory mechanisms; however, the extent to which sex plays a role in the relationship between the circadian timing of behaviors and markers of inflammation is unclear. We investigated sex-specific associations between circadian alignment, variability in sleep timing, and inflammatory markers in healthy adults. Forty-two volunteers (23 female) underwent an evening in-laboratory dim-light melatonin onset (DLMO) assessment. Plasma C-reactive protein (CRP; all participants) and tumor necrosis factor-α (TNF-α; subset <i>n</i> = 27 [13 female]) were assayed. Circadian alignment (i.e., phase angle) was determined as the time difference between DLMO and average sleep onset for up to 14 days. Participants were categorized into narrow/wide phase angle groups based on median phase angle split. Variability in sleep timing was defined as the standard deviation (SD) of self-reported sleep onset and offset times. Within sex differences in inflammatory markers were compared between phase angle groups. Linear models were used to test the interaction between sex, circadian alignment, and sleep timing variability on markers of inflammation. Females in the narrow phase angle group had higher CRP, whereas males with narrow phase angles had higher TNF-α (<i>P</i> < 0.01). Increased CRP was associated with a narrower phase angle [β(SE) = -0.69 (0.25), <i>P</i> = 0.01] and greater sleep offset timing variability [β(SE) = 2.00 (0.68, <i>P</i> < 0.01)] in females, whereas TNF-α was associated with a narrower phase angle [β(SE) = -0.11 (0.05), <i>P</i> = 0.04] in males. Circadian disruptions and more variable sleep patterns could contribute to inflammatory-related CVD pathology, particularly as it pertains to sex. These data may have implications for sex-specific disease risk assessment and risk reduction strategies.<b>NEW & NOTEWORTHY</b> Disturbances to sleep and the circadian timing system have significant implications for cardiovascular health. Inflammatory markers have been shown to be predictive of CVD risk; however, the extent to which circadian disturbances and sleep timing contribute to sex-specific markers of inflammation is unclear. In this study, we leverage in-laboratory and outpatient biobehavioral data collection to show that the relationships between circadian disruptions and/or sleep timing variability may be differentially linked to inflammatory markers by sex.