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Aims  To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women. Methods and results  We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01–2.42), P = 0.038; SHHS-women: HR 1.21 (1.06–1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04–4.50), P = 0.037; SHHS-women: HR 1.60 (1.12–2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94–1.32), P = 0.261; SHHS-men: HR 1.31 (1.06–1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02–1.79), P = 0.034; SHHS-men: HR 1.24 (0.86–1.79), P = 0.271] was less clear. Conclusions Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.

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The dynamic interplay between central and autonomic nervous system activities plays a pivotal role in orchestrating sleep. Macrostructural changes such as sleep-stage transitions or phasic, brief cortical events elicit fluctuations in neural outflow to the cardiovascular system, but the causal relationships between cortical and cardiovascular activities underpinning the microstructure of sleep are largely unknown. Here, we investigate cortical–cardiovascular interactions during the cyclic alternating pattern (CAP) of non-rapid eye movement sleep in a diverse set of overnight polysomnograms. We determine the Granger causality in both 507 CAP and 507 matched non-CAP sequences to assess the causal relationships between electroencephalography (EEG) frequency bands and respiratory and cardiovascular variables (heart period, respiratory period, pulse arrival time and pulse wave amplitude) during CAP. We observe a significantly stronger influence of delta activity on vascular variables during CAP sequences where slow, low-amplitude EEG activation phases (A1) dominate than during non-CAP sequences. We also show that rapid, high-amplitude EEG activation phases (A3) provoke a more pronounced change in autonomic activity than A1 and A2 phases. Our analysis provides the first evidence on the causal interplay between cortical and cardiovascular activities during CAP. Granger causality analysis may also be useful for probing the level of decoupling in sleep disorders. This article is part of the theme issue ‘Advanced computation in cardiovascular physiology: new challenges and opportunities’.

Study Objectives To determine in children with obstructive sleep apnea (OSA) the effect of adenotonsillectomy on the cyclic alternating pattern (CAP) and the relationship between CAP and behavioral, cognitive, and quality-of-life measures. Methods CAP parameters were analyzed in 365 overnight polysomnographic recordings of children with mild-to-moderate OSA enrolled in the Childhood Adenotonsillectomy Trial (CHAT), randomized to either early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC). We also analyzed CAP in a subgroup of 72 children with moderate OSA (apnea-hypopnea index>10) that were part of the CHAT sample. Causal mediation analysis was performed to determine the independent effect of changes in CAP on selected outcome measures. Results At baseline, a higher number of A1-phases per hour of sleep was significantly associated with worse behavioral functioning (caregiver BRIEF GCE: ρ=0.24, P=0.042; caregiver Conners’ Rating Scale Global Index: ρ=0.25, P=0.036) and lower quality of life (OSA-18: ρ=0.27, P=0.022; PedsQL: ρ=-0.29, P=0.015) in the subgroup of children with moderate OSA, but not across the entire sample. At 7-months follow-up, changes in CAP parameters were comparable between the eAT and WWSC arms. CAP changes did not account for significant proportions of variations in behavioral, cognitive and quality-of-life performance measures at follow-up. Conclusions We show a significant association between the frequency of slow, high-amplitude waves with behavioral functioning as well as the quality-of-life in children with moderate OSA. Early adenotonsillectomy in children with mild-to-moderate OSA does not alter the microstructure of NREM sleep compared to watchful waiting after an approximately 7 month period of follow-up. Clinical Trial The study “A Randomized Controlled Study of Adenotonsillectomy for Children With Obstructive Sleep Apnea Syndrome” was registered at Clinicaltrials.gov (#NCT00560859).