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Background: The healthy adherer effect has gained increasing attention as a potential source of bias in observational studies examining the association of positive airway pressure (PAP) adherence with health outcomes in OSA., Research Question: Is adherence to PAP associated with healthy behaviors and health care resource use prior to device prescription?, Study Design and Methods: Data from the Institut de Recherche en Santé Respiratoire (IRSR) des Pays de la Loire Sleep Cohort were linked to health administrative data to identify proxies of heathy behaviors, including adherence to cardiovascular (CV) drugs (medical possession ratio), cancer screening tests, influenza vaccination, alcohol and smoking consumption, and drowsiness-related road accidents during the 2 years preceding PAP onset in patients with OSA. Multivariable regression analyses were conducted to evaluate the association of heathy behaviors with subsequent PAP adherence. Health care resource use was evaluated according to subsequent PAP adherence., Results: We included 2,836 patients who had started PAP therapy between 2012 and 2018 (65% of whom were PAP adherent with mean daily use ≥ 4 h/night). Being adherent to CV active drugs (medical possession ratio ≥ 80%) and being a person who does not smoke were associated with a higher likelihood of PAP adherence (OR, 1.43; 95% CI, 1.15-1.77 and OR, 1.37; 95% CI, 1.10-1.71, respectively). Patients with no history of drowsiness-related road accidents were more likely to continue PAP (OR, 1.39; 95% CI, 1.04-1.87). Patients who were PAP adherent used less health care resources 2 years before PAP initiation than patients who were nonadherent (mean number of outpatient consultations: 19.0 vs 17.2, P = .003; hospitalization days: 5.7 vs 5.0; P = .04; ED visits: 30.7% vs 24.0%, P = .0002, respectively)., Interpretation: This study indicated that patients who adhere to PAP therapy for OSA were more health-seeking and used less health care resources prior to device initiation than patients who were nonadherent. Until the healthy adherer effect associated with PAP adherence is better understood, caution is warranted when interpreting the association of PAP adherence with CV health outcomes and health care resource use in nonrandomized cohorts., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: C. L. reports lecture honoraria from Resmed. W. T. reports lecture honoraria from Astra Zeneca and travel support from Asten. F. Gagnadoux reports grants from Resmed; consulting fees from Resmed, Sefam, Inspire, and bioprojet; lecture honoraria from Philips Respironics, Inspire, Resmed, Bioprojet, and Asten Sante; and travel support from Asten Sante, MSD, and Bioprojet. None declared (S. B., A. S., T. P., C. H., P. M., A. B.-T., N. M., S. K., F. Goupil)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  Previous studies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and incident venous thromboembolism (VTE). More specifically, the association between OSA and unprovoked VTE was barely evaluated. We aimed to evaluate whether apnea hypopnea index (AHI) and nocturnal hypoxemia markers were associated with unprovoked VTE incidence in patients investigated for OSA., Material and Methods:  Data from the Pays de la Loire Sleep Cohort were linked to the French health administrative data to identify incident unprovoked VTE in patients suspected for OSA and no previous VTE disease. Cox proportional hazards models were used to evaluate the association of unprovoked VTE incidence with AHI and nocturnal hypoxemia markers including the time spent under 90% of saturation (T90), oxygen desaturation index, and hypoxic burden (HB), a more specific marker of respiratory events related to hypoxia. The impact of continuous positive airway pressure (CPAP) was evaluated in the subgroup of patients who were proposed the treatment., Results:  After a median [interquartile range] follow-up of 6.3 [4.3-9.0] years, 104 of 7,355 patients developed unprovoked VTE, for an incidence rate of 10.8 per 1,000 patient-years. In a univariate analysis, T90 and HB predicted incident VTE. In the fully adjusted model, T90 was the only independent predictor (hazard ratio: 1.06; 95% confidence interval: [1.01-1.02]; p  = 0.02). The CPAP treatment has no significant impact on VTE incidence., Conclusion:  Patients with more severe nocturnal hypoxia are more likely to have incident unprovoked VTE., Competing Interests: W.T. reports support for attending meetings by ASTEN SANTE. C.G.-P. has nothing to disclose. B.H. has nothing to disclose. M.B. has nothing to disclose. N.M. reports support for attending meetings by ASTEN SANTE. M.J. has nothing to disclose. S.K. has nothing to disclose. R.L.M. received support for attending meetings by Astra Zeneca, GSK and Orkyn, and consulting fees from Astra Zeneca and GSK, outside the submitted work. E.M. has nothing to disclose. J.-L.R. has nothing to disclose. A.S. has nothing to disclose. J.T. received fees from Laboratoire Pierre Fabres, outside the submitted work. F.C. received consulting fees from Bayer, Pfizer, Astra, MSD, GSK, Leopharma, outside the submitted work. F.G. received support for attending meetings by ASTEN SANTE and ACTELION and consulting fees from NYXOAH, SEFAM, RESMED, CIDELEC, ASTEN SANTE, and BOEHRINGER INGELHEIM, outside the submitted work., (Thieme. All rights reserved.)

Rationale: Randomized controlled trials showed no effect of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on cardiovascular (CV) risk. However, patient selection and low PAP adherence preclude the generalization of their data to clinical samples. Objectives: To evaluate the association between hours of PAP use, mortality, and CV morbidity in real-life conditions. Methods: Data from the Pays de la Loire Cohort were linked to health administrative data to identify incident major adverse cardiovascular events (MACEs; a composite outcome of mortality, stroke, and cardiac diseases) in patients with OSA who were prescribed PAP. Cox proportional hazards analyses were conducted to evaluate the association between MACEs and quartiles of average daily PAP use over the study period. Measurements and Main Results: After a median follow-up of 6.6 years, 961 of 5,138 patients experienced MACEs. Considering nonadherent patients (0-4 h/night) as the reference group, adjusted hazard ratios (95% confidence intervals) for MACEs were 0.87 (0.73-1.04) for the 4-6 h/night group, 0.75 (0.62-0.92) for the 6-7 h/night group, and 0.78 (0.65-0.93) for the ⩾7 h/night group ( P  = 0.0130). Sensitivity analyses using causal inference approaches confirmed the association of PAP use with MACEs. The association was stronger in male patients ( P value for interaction = 0.0004), patients without overt CV disease at diagnosis ( P  < 0.0001), and those belonging to the excessively sleepy symptom subtype ( P  = 0.060). Conclusions: These real-life clinical data demonstrate a dose-response relationship between PAP adherence and incident MACEs in OSA. Patient support programs may help improve PAP adherence and CV outcomes in patients with OSA.

Background: Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA., Methods: The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk., Results: After a median (interquartile range) follow-up of 5.4 (3.1-8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78-1.14)., Conclusions: Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated., Competing Interests: Conflict of interest: G. Justeau has nothing to disclose. Conflict of interest: S. Bailly reports consulting fees for methodology and statistical analyses from Institut Recherche en Santé Respiratoire des Pays de la Loire, outside the submitted work. Conflict of interest: C. Gervès-Pinquié has nothing to disclose. Conflict of interest: W. Trzepizur has nothing to disclose. Conflict of interest: N. Meslier has nothing to disclose. Conflict of interest: F. Goupil has nothing to disclose. Conflict of interest: T. Pigeanne has nothing to disclose. Conflict of interest: S. Launois has nothing to disclose. Conflict of interest: L. Leclair-Visonneau has nothing to disclose. Conflict of interest: P. Masson has nothing to disclose. Conflict of interest: A. Bizieux-Thaminy has nothing to disclose. Conflict of interest: J-L. Racineux has nothing to disclose. Conflict of interest: D. Gozal reports NIH grants, outside the submitted work. Conflict of interest: F. Gagnadoux reports support for the present manuscript from Institut Recherche en Santé Respiratoire des Pays de la Loire to the University Hospital of Angers; consulting fees from Nyxoah, Sefam and ResMed; payment or honoraria for lectures from Cidelec, Asten Santé and Boehringer Ingelheim; payment for expert testimony from Boehringer Ingelheim; support for attending meetings and/or travel from Asten Santé and Actelion; participation on a data safety monitoring board or advisory board for Jazz Pharmaceutical; receipt of equipment, materials, drugs, medical writing, gifts or other services from Inspire to the University Hospital of Angers, outside the present work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation <90% were the only predictors of MACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.

Objective . Cardiovascular disease (CVD) is one of the leading causes of death worldwide. There are many CVD risk estimators but very few take into account sleep features. Moreover, they are rarely tested on patients investigated for obstructive sleep apnea (OSA). However, numerous studies have demonstrated that OSA index or sleep features are associated with CVD and mortality. The aim of this study is to propose a new simple CVD and mortality risk estimator for use in routine sleep testing. Approach . Data from a large multicenter cohort of CVD-free patients investigated for OSA were linked to the French Health System to identify new-onset CVD. Clinical features were collected and sleep features were extracted from sleep recordings. A machine-learning model based on trees, AdaBoost, was applied to estimate the CVD and mortality risk score. Main results . After a median [inter-quartile range] follow-up of 6.0 [3.5-8.5] years, 685 of 5234 patients had received a diagnosis of CVD or had died. Following a selection of features, from the original 30 features, 9 were selected, including five clinical and four sleep oximetry features. The final model included age, gender, hypertension, diabetes, systolic blood pressure, oxygen saturation and pulse rate variability (PRV) features. An area under the receiver operating characteristic curve (AUC) of 0.78 was reached. Significance . AdaBoost, an interpretable machine-learning model, was applied to predict 6 year CVD and mortality in patients investigated for clinical suspicion of OSA. A mixed set of simple clinical features, nocturnal hypoxemia and PRV features derived from single channel pulse oximetry were used., (© 2021 Institute of Physics and Engineering in Medicine.)

Purpose: We aimed to determine the risk factors of sleepiness at the wheel among patients with obstructive sleep apnea (OSA) and to determine factors that were independently associated with reported sleep-related near-miss accidents or car accidents., Patients and Methods: This retrospective study was conducted on 843 OSA patients from the French Pays de la Loire sleep cohort database. Each patient completed surveys including anthropometric data, medical history, professional status, and data on alcohol and tobacco use. Epworth sleepiness scale (ESS) and sleep quality questionnaires were administered. Regarding driving, data were collected on occurrence of sleepiness-related near-misses or car accidents, and on distance driven per year. The primary dependent variable of interest was reported sleepiness at the wheel., Results: On multivariable regression analysis, reported sleepiness at the wheel (n=298) was independently associated with younger age (p=0.02), male gender (p=0.009), marked nocturnal hypoxemia (p=0.006), lower BMI (p=0.03), absence of cardiovascular disease (p=0.022), executives or high degree jobs (p=0.003) and reported difficulty-maintaining sleep (p=0.03). Only past experience of sleepiness at the wheel (OR 12.18, [6.38-23.25]) and an ESS ≥11 (OR 4.75 [2.73-8.27]) were independently associated with reported car accidents (n=30) or near-miss accidents (n=137)., Conclusion: In patients newly diagnosed with OSA, the risk of car accident seems multifactorial, and its evaluation should include multiple parameters such as patient self-reported sleepiness at the wheel, occurrence of sleepiness-related accidents, anthropometry, professional status, and insomnia complaints. Thus, it is possible to evaluate this risk and advise patients as early as the first visit at the sleep medicine clinic without waiting for the results of the sleep study., Competing Interests: Professor Pierre Philip reports personal fees, non-financial support from Jazz, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Sabil et al.)

Rationale: Nocturnal hypoxemia and sympathetic/parasympathetic imbalance might contribute to the occurrence or atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA). During sleep recordings, pulse rate variability (PRV) derived from oximetry might provide an accurate estimation of heart rate variability, which reflects the autonomic cardiovascular control. Objectives: We aimed to evaluate whether indices of oxygen desaturation and PRV derived from nocturnal oximetry were associated with AF incidence in patients investigated for OSA. Methods: Data from a large multicenter cohort of AF-free patients investigated for OSA between May 15, 2007, and December 31, 2017, were linked to health administrative data to identify hospitalized and nonhospitalized patients with new-onset AF. Cox proportional hazards models were used to evaluate the association between AF incidence and oximetry-derived indices automatically generated from sleep recordings. Results: After a median (interquartile range) follow-up of 5.34 (3.3-8.0) years, 181 of 7,205 patients developed AF (130 were hospitalized for AF). After adjusting for confounders, including anthropomorphic data, alcohol intake, cardiac, metabolic and respiratory diseases, β blocker/calcium channel blocker medications, type of sleep study, study site, and positive airway pressure adherence, AF risk was associated with increasing nocturnal hypoxemia ( P trend = 0.004 for quartiles of percentage of recording time with oxygen saturation <90%) and PRV ( P trend < 0.0001 for quartiles of root mean square of the successive normal-normal beat interval differences), and decreasing sympathetic/parasympathetic tone ( P trend = 0.0006 for quartiles of low-frequency power/high-frequency power ratio). The highest risk of AF was observed in patients with the highest quartiles of both the percentage of recording time with oxygen saturation <90% and the root mean square of the successive normal-normal beat interval differences compared with those with neither of these conditions (adjusted hazard ratio, 3.61; 95% confidence interval, 2.10-6.22). Similar associations were observed when the analyses were restricted to hospitalized AF. Conclusions: In patients investigated for OSA, nocturnal hypoxemia and PRV indices derived from single-channel pulse oximetry were independent predictors of AF incidence. Patients with both marked nocturnal hypoxemia and high PRV were at higher risk of AF. Oximetry may be used to identify patients with OSA at greatest risk of developing AF.

Study Objectives: To assess, in a large cohort of patients with obstructive sleep apnea, the factors that are independently associated with positional obstructive sleep apnea (POSA) and exclusive POSA (e-POSA) and determine their prevalence. The secondary objective was to evaluate the outcome of positive airway pressure (PAP) therapy for patients with POSA and e-POSA., Methods: This retrospective study included 6,437 patients with typical mild-to-severe OSA from the Pays de la Loire sleep cohort. Patients with POSA and e-POSA were compared to those with non-POSA for clinical and polysomnographic characteristics. In a subgroup of patients (n = 3,000) included in a PAP follow-up analysis, we determined whether POSA and e-POSA phenotypes were associated with treatment outcomes at 6 months., Results: POSA and e-POSA had a prevalence of 53.5% and 20.1%, respectively, and were independently associated with time in supine position, male sex, younger age, lower apnea-hypopnea index and lower body mass index. After adjustment for confounding factors, patients with POSA and e-POSA had a significantly lower likelihood of treatment adherence (PAP daily use ≥ 4 h) at 6 months and were at higher risk of PAP treatment withdrawal compared to those with non-POSA., Conclusions: The prevalence and independent predictors of POSA and e-POSA were determined in this large clinical population. Patients with POSA and e-POSA have lower PAP therapy adherence, and this choice of treatment may not be optimal. Thus, there is a need to offer these patients an alternative therapy., (© 2020 American Academy of Sleep Medicine.)

Background: Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans., Research Question: Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA?, Study Design and Methods: Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia., Results: After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P < .0005) and nocturnal hypoxemia (log-rank test, P < .0001 for both oxygen desaturation index and percent night time with oxygen saturation < 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs < 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies., Interpretation: Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)