Circadian Misalignment is Associated With Impaired Heart Rate Variability in Adolescents

Introduction: Adequate sleep has been recognized by AHA as part of Life’s Essential 8 in the prevention of cardiovascular disease (CVD). The circadian system, which governs the sleep-cycle, is also involved in cardiac, metabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict CVD. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may impact CAM and be a potential risk factor for adverse CVD outcomes in early life. Hypothesis: We hypothesize that deviations in the circadian timing of sleep are associated with blunted HRV in adolescents. Methods: We analyzed data from 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-sleep duration and sleep midpoint (SM) were calculated as the intra-individual mean total sleep time and midpoint of the sleep period, respectively. ACT-sleep variability and sleep regularity (SR) were calculated as the intra-individual standard deviation of sleep duration and sleep midpoint across nights, respectively. Frequency and time-domain HRV indices, including HR oscillations at high frequencies (HF), standard deviation between normal heart beats or R-R intervals (SDNN), and root mean square of successive differences between normal heartbeats (RMSSD), were primary outcomes. Linear regression models tested SM and SR as predictors of HRV indices, while accounting for sex, race/ethnicity, age, body mass index, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results: While there were no meaningful associations between SM or SR with daytime HRV, there were significant associations between SM with nighttime HRV. A later SM was associated with lower nighttime Log-HF, SDNN and RMSSD, yet higher nighttime LF/HF (all p<0.03). For each standard deviation increase in SM (i.e., 1.5 hours later), there was a decrease of -5.50ms (1.92) in nighttime RMSSD (p=0.004). More specifically, the nighttime RMSSD of adolescents with a SM at 5:30 (i.e., sleep onset at 2:00, sleep offset at 9:00), was 18.2ms (6.7) lower (p=0.007) than that of adolescents with a SM at 2:30 (i.e., sleep onset at 23:00, sleep offset at 6:00). Conclusions: A delayed sleep phase is associated with impaired CAM in adolescents. These data support that circadian misalignment of the sleep-wake cycle may independently contribute to CVD risk.