LAUSR

The circadian timing system, which governs the sleep-wake cycle, is involved in cardiometabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict cardiovascular morbidity. Therefore, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents and may express differently if youth are in school or free-days, is likely to impact CAM. We examined whether deviations in the circadian timing of sleep are associated with blunted HRV in adolescents as a function of being entrained to school or not. We studied 337 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-measured sleep midpoint (SM) was calculated as the midpoint of the sleep period for weekdays (5-nights) and weekends (2-nights), whereas ACT-measured sleep regularity (SR) was calculated as the intra-individual standard deviation of the SM across 5- and 7-nights. Frequency and time-domain HRV indices were primary outcomes. Linear regression models were stratified by “in school” and “on break” to test SM and SR as predictors of HRV indices while accounting for sex, race/ethnicity, age, BMI percentile, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Lower SR on schooldays was associated with lower nighttime Log-HF, Log-LF and SDNN, yet higher HR (all p< 0.01); e.g., each standard deviation increase in SR on schooldays (i.e., 45m higher) was associated with -7.15ms (2.57) in nighttime SDNN (p=0.006). A later SM on free weekends was associated with lower nighttime Log-HF, Log-LF, SDNN and RMSSD, yet higher HR and LF-HF ratio (all p< 0.03); e.g., each standard deviation increase in SM on free weekends (i.e., 1.5h later) was associated with -7.33ms (2.85) in nighttime RMSSD (p=0.011). A delayed and an irregular sleep midpoint during breaks and during schooldays, respectively, were associated with impaired CAM in adolescents. These data suggest that not only circadian misalignment contributes to adverse cardiovascular outcomes but its distinct metrics require measurement under different entrainment conditions in adolescents. NIH (R01HL136587,R01MH118308,UL1TR000127), American Heart Association (23PRE1011962).