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Context: Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear.Objective: To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA.Design, Setting, and Patients: Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009.Intervention: Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice.Main Outcome Measures: Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).Results: Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20).Conclusions: In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference.Trial Registration: clinicaltrials.gov Identifier: NCT00127348. [ABSTRACT FROM AUTHOR]

RATIONALE: Home respiratory polygraphy (HRP) is an alternative to polysomnography (PSG) for sleep apnea-hypopnea syndrome (SAHS) diagnosis. However, therapeutic decision-making is a different process than diagnosis. OBJECTIVES: This study aimed to determine the agreement between HRP and in-hospital PSG for therapeutic decision-making in a large sample. METHODS: Patients with an intermediate or high SAHS suspicion were included in a multicenter study (eight sleep centers) and assigned to home and hospital protocols in a random order. Therapeutic decisions (continuous positive airway pressure, no continuous positive airway pressure, or impossible decision) were made by an investigator in each center, based on using either HRP or PSG and a single set of auxiliary clinical variables. Patients and diagnostic methods (HRP and PSG) were assessed in random order using an electronic database. After a month the same therapeutic decision-making procedure was repeated with the same method. MEASUREMENTS AND MAIN RESULTS: Of 366 randomized patients, 348 completed the protocol. The 'impossible decision' case was not observed with either PSG or HRP. Therapeutic decisions using HRP had a sensitivity of 73%, a specificity of 77%, and an agreement level (sum of true positives and negatives) of 76%. Patients with higher HRP apnea-hypopnea index (AHI) scores (>= 30; 41% of the total sample) had a sensitivity of 94%, a specificity of 44%, and the agreement level was 91%. CONCLUSIONS: The HRP-based therapeutic decision was adequate when AHI was high, but deficient in the large population of patients with mild to moderate AHI. Therefore, both selecting patients with a high suspicion and severity of SAHS and future prospective cost-effectiveness studies are necessary. [ABSTRACT FROM AUTHOR]

RATIONALE: Continuous positive airway pressure (CPAP) is the current treatment for patients with symptomatic obstructive sleep apnea (OSA). Its use for all subjects with sleep-disordered breathing, regardless of daytime symptoms, is unclear. Objectives: This multicenter controlled trial assesses the effects of 1 year of CPAP treatment on blood pressure (BP) in nonsymptomatic, hypertensive patients with OSA. METHODS: We evaluated 359 patients with OSA. Inclusion criteria consisted of an apnea-hypopnea index (AHI) greater than 19 hour(-1), an Epworth Sleepiness Scale score less than 11, and one of the following: under antihypertensive treatment or systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 mm Hg. Patients were randomized to CPAP (n = 178) or to conservative treatment (n = 181). BP was evaluated at baseline and at 3, 6, and 12 months of follow-up. MEASUREMENTS AND MAIN RESULTS: Mean (SD) values were as follows: age, 56 +/- 10 years; body mass index (BMI), 32 +/- 5 kg x m(-2); AHI, 45 +/- 20 hour(-1); and Epworth Sleepiness Scale score, 7 +/- 3. After adjusting for follow-up time, baseline blood pressure values, AHI, time with arterial oxygen saturation less than 90%, and BMI, together with the change in BMI at follow-up, CPAP treatment decreased systolic blood pressure by 1.89 mm Hg (95% confidence interval: -3.90, 0.11 mm Hg; P = 0.0654), and diastolic blood pressure by 2.19 mm Hg (95% confidence interval: -3.46, -0.93 mm Hg; P = 0.0008). The most significant reduction in BP was in patients who used CPAP for more than 5.6 hours per night. CPAP compliance was related to AHI and the decrease in Epworth Sleepiness Scale score. CONCLUSIONS: In nonsleepy hypertensive patients with OSA, CPAP treatment for 1 year is associated with a small decrease in BP. This effect is evident only in patients who use CPAP for more than 5.6 hours per night. Clinical trial registered with www.clinicaltrials.gov (NCT00127348). [ABSTRACT FROM AUTHOR]

Standard practice for continuous positive airway pressure (CPAP) treatment in sleep apnea and hypopnea syndrome (SAHS) requires pressure titration during attended laboratory polysomnography. However, polysomnographic titration is expensive and time-consuming. The aim of this study was to ascertain, in a large sample of CPAP-naive patients, whether CPAP titration performed by an unattended domiciliary autoadjusted CPAP device or with a predicted formula was as effective as CPAP titration performed by full polysomnography. The main outcomes were the apnea-hypopnea index and the subjective daytime sleepiness. We included 360 patients with SAHS requiring CPAP treatment. Patients were randomly allocated into three groups: standard, autoadjusted, and predicted formula titration with domiciliary adjustment. The follow-up period was 12 weeks. With CPAP treatment, the improvement in subjective sleepiness and apnea-hypopnea index was very similar in the three groups. There were no differences in the objective compliance of CPAP treatment and in the dropout rate of the three groups at the end of the follow-up. Autoadjusted titration at home and predicted formula titration with domiciliary adjustment can replace standard titration. These procedures could lead to considerable savings in cost and to significant reductions in the waiting list. [ABSTRACT FROM AUTHOR]

Background: The sleep apnea-hypopnea syndrome is defined by a pathologic number of respiratory events during sleep (the apnea-hypopnea index, defined as the number of apnea and hypopnea episodes per hour) and daytime symptoms (mostly, excessive sleepiness). In patients with the sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP) normalizes both the apnea-hypopnea index and diurnal symptoms. However, the effect of CPAP in persons with a pathologic apnea-hypopnea index without daytime sleepiness is unclear.Objective: To investigate the short-term effects of CPAP on quality of life, objective sleepiness, cognitive function, and arterial blood pressure in nonsleepy patients with a pathologic apnea-hypopnea index.Design: Multicenter randomized, placebo-controlled, parallel-group study.Setting: Six teaching hospitals in Spain.Patients: 55 patients with an apnea-hypopnea index of 30 or greater who did not have daytime sleepiness (Epworth Sleepiness Scale score Intervention: Patients were randomly assigned to receive optimal (n = 29) or sham (n = 25) CPAP and were observed for 6 weeks.Measurements: Quality of life, objective sleepiness (Multiple Sleep Latency Test score), cognitive function, and arterial blood pressure.Results: The intervention and control groups were similar in terms of mean (+/-SE) age (54 +/- 2 vs. 52 +/- 2 years), apnea-hypopnea index (54 +/- 3 vs. 57 +/- 4), Epworth Sleepiness Scale score (7.0 +/- 0.4 vs. 7.0 +/- 0.4) and adherence to CPAP treatment (5.0 +/- 0.4 vs. 4.0 +/- 0.5 hours/d). Other variables, such as quality of life, cognitive function, and arterial blood pressure, were also similar in both groups before treatment. After 6 weeks of CPAP or sham CPAP, none of these variables changed significantly.Conclusion: In patients with an apnea-hypopnea index of 30 or greater and no subjective daytime sleepiness, CPAP does not modify quality of life, objective sleepiness, vigilance, attention, memory, information processing, visuomotor coordination, or arterial blood pressure. Treatment with CPAP is therefore not indicated in nonsleepy patients with a pathologic apnea-hypopnea index. [ABSTRACT FROM AUTHOR]

Rationale: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated., Objective: To characterize the molecular pathways that relate OSA with CVE recurrence., Methods: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology., Results: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m 2 ). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes., Conclusion: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients., Methods: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years., Results: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m 2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects., Conclusions: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking., Methods: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed., Results: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h -1 . The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up., Conclusion: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients., Competing Interests: Conflict of interest: F. Barbé received research grants from Philips Respironics Inc. and ResMed (companies that develop products related to sleep apnoea), the Health Research Fund, the Spanish Ministry of Health, and the Spanish Respiratory Society to develop the SARAH study. Philips Respironics Inc. and ResMed partly funded the SARAH study but did not participate in nor were they involved in decisions regarding study development or the present manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored., Research Question: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma?, Study Design and Methods: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome., Results: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90)., Interpretation: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To evaluate the impact of positive airway pressure (PAP) therapy on body mass index (BMI) in patients with obesity hypoventilation syndrome (OHS) associated with obstructive sleep apnea (OSA)., Methods: A systematic review using the following terms: "obesity hypoventilation syndrome" AND "treatment" AND "randomized" using Cochrane Central Register of Controlled Trials, Medline and Web of Science was performed from the first data available until February 10, 2023. The inclusion criteria were: (1) original article; (2) adult OHS with concomitant OSA (apnea-hypopnea index or AHI ≥5 events/h); (3) randomized trial with PAP arm and standard care (control); (4) BMI evaluation at baseline and after the first months. We performed an individual participant data meta-analysis of randomized controlled trials., Results: Our initial search retrieved 32 articles and 3 randomized studies fulfilled study criteria and were included in the final analysis, leading to a total of 342 participants. Patients were predominantly females (62%) and had OHS associated with at least mild OSA. As compared to baseline, a decrease in BMI was observed at study endpoint but this difference was not different intergroups (-0.50 ± 1.49 and -0.50 ±1.83, in control and PAP groups respectively (p=0.939)). Weight change was not associate with PAP adherence, OSA severity or use of supplemental oxygen., Conclusions: In contrast to treatment of eucapnic OSA with PAP that is associated with weight gain, treatment of OSA+OHS patients with or without PAP is associated with weight loss. Future studies are necessary to elucidate the mechanism by which weight loss occurs., Competing Interests: Conflicts of interest No potential conflict of interest exists with any companies/organizations whose products or services may be discussed in this article., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea-hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases., Methods: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE., Results: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m 2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems., Conclusion: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management., Competing Interests: Conflict of interest statement FB received a research grant from ResMed (an Australian company that develops products related to sleep apnea), the Health Research Fund, the Spanish Ministry of Health, the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin (Spain), Oxigen Salud (Spain), and ALLER to develop the ISAACC trial. ResMed partly funded the ISAACC study but did not participate in nor was involved in decisions regarding study development or the present manuscript. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Rationale: Obstructive sleep apnea (OSA) is prevalent in patients with acute coronary syndrome (ACS) and is a cause of secondary hypertension. Objectives: To explore the long-term effects of OSA and continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in patients with ACS. Methods: Post hoc analysis of the ISAACC study (Continuous Positive Airway Pressure in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea; NCT01335087) included 1,803 patients admitted for ACS. Patients with OSA (apnea-hypopnea index [AHI], ⩾15 events/h) were randomly assigned to receive either CPAP or usual care and were seen in follow-up for 1-5 years. Office BP was determined at each visit. Results: We included 596 patients without OSA, 978 patients in the usual care or poor CPAP adherence group, and 229 patients in the good CPAP adherence group. At baseline, 52% of the patients were diagnosed with hypertension. Median (25th to 75th percentile) age and body mass index were 59 (52.0 to 67.0) years and 28.2 (25.6 to 31.2) kg/m 2 , respectively. After a median (25th to 75th percentile) follow-up of 41.2 (18.3 to 59.6) months, BP changes were similar in the OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI, >40 events/h), with a maximum difference in mean BP of +3.3 mm Hg at 30 months. Patients with OSA with good CPAP adherence (⩾4 h/night) reduced mean BP after 18 months compared with patients with usual care/poor CPAP adherence, with a maximum mean difference (95% confidence interval) of -4.7 (-6.7 to -2.7) mm Hg. In patients with severe OSA, we observed a maximum mean difference of -7.1 (-10.3 to -3.8) mm Hg. Conclusions: In patients with ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT01335087).

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS., Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO 2 ), average duration of events and percentage of time with SaO 2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components., Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO 2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO 2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p -value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events., Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zapater, Solelhac, Sánchez-de-la-Torre, Gracia-Lavedan, Benitez, Torres, De Batlle, Haba-Rubio, Berger, Abad, Duran-Cantolla, Urrutia, Mediano, Masdeu, Ordax-Carbajo, Masa, De la Peña, Mayos, Coloma, Montserrat, Chiner, Mínguez, Pascual, Cortijo, Martínez, Dalmases, Lee, McEvoy, Barbé, Heinzer and Sánchez-de-la-Torre.)

Rationale: Primary care clinicians may be well placed to play a greater role in obstructive sleep apnea (OSA) management. Objectives: To evaluate the outcomes and cost-effectiveness of sleep apnea management in primary versus specialist care, using an individual-participant data meta-analysis to determine whether age, sex, severity of OSA, and daytime sleepiness impacted outcomes. Methods: Data sources were the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP, Scopus, ProQuest, U.S. National Institutes of Health Ongoing Trials Register, and ISRCTN registry (inception until 09-25-2019). Hand searching was undertaken. Two authors independently assessed articles and included trials that randomized adults with a suspected diagnosis of sleep apnea to primary versus specialist management within the same study and reported daytime sleepiness using the Epworth Sleepiness Scale (range 0-24; >10 indicates pathological sleepiness; minimum clinically important difference 2 units) at baseline and follow-up. Results: The primary analysis combined data from 970 (100%) participants (four trials). Risk of bias was assessed (Cochrane Tool). One-stage intention-to-treat analysis showed a slightly smaller decrease in daytime sleepiness (0.8; 0.2 to 1.4), but greater reduction in diastolic blood pressure in primary care (-1.9; -3.2 to -0.6 mm Hg), with similar findings in the per-protocol analysis. Primary care-based within-trial healthcare system costs per participant were lower (-$448.51 U.S.), and quality-adjusted life years and daytime sleepiness improvements were less expensive. Similar primary outcome results were obtained for subgroups in both management settings. Conclusions: Similar outcomes in primary care at a lower cost provide strong support for implementation of primary care-based management of sleep apnea.

Study Objectives: Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS., Methods: In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a P value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea., Results: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO 2 and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98; P = .003 for PaO 2 , and 1.07; 95% confidence interval 1.03 to 1.12; P = .001 for body mass index). In separate analyses, body mass index and PaO 2 were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype., Conclusions: This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population., Clinical Trial Registration: Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976., Citation: Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome. J Clin Sleep Med . 2022;18(4):983-992., (© 2022 American Academy of Sleep Medicine.)

Rationale: Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity., Objective: To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups., Methods: Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI)≥30events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO 2 of 45-49.9 or ≥50mmHg). Repeated measures of PaCO 2 and PaO 2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model., Results: 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO 2 and PaO 2 were similar between CPAP and NIV based on the PaCO 2 severity subgroups., Conclusion: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO 2 ., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558)., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Respiratory high dependency units (RHDUs) set up in European countries in the last decade are based on being a transitional step between the intensive care units (ICUs) and the conventional hospital ward in terms of staffing, level of monitoring, and patients' severity. In the pre-COVID-19 era, its main use has been the treatment of hypercapnic acute-on-chronic respiratory failure with noninvasive respiratory support, and more recently, for hypoxemic acute respiratory failure., Areas Covered: We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, limited to the terms: COVID-19 and RHDU, Respiratory Intermediate care Unit, acute respiratory distress syndrome (ARDS), noninvasive ventilation (NIV), high flow nasal cannula (HFNC), prone position, and monitoring. In this review, we summarize RHDU´s dual purpose: on the one hand, to decrease the number of admissions into ICU, and on the other hand, early discharges of patients from ICU with prolonged admissions due to the need of care or laborious weaning from invasive mechanical ventilation. Although this dual purpose of RHDUs has contributed to decrease the overload of the ICUs during the pandemic, the hundreds of patients admitted in hospitals, with approximately 20%-30% needing critical care, has exceeded the forecasts of many hospitals., Expert Opinion: It seems clear that a reorganization and optimization of the care of patients with severe COVID-19 is necessary, minimizing admissions to the ICU and facilitating an early discharge. During the pandemic, several hospitals have spontaneously created new RHDUs or extended preexisting RHDUs or up-graded respiratory wards in order to receive less sick patients requiring lower levels of monitoring and nurse-to-patient ratios. This article reviews under a European expert perspective this topic and proposes an adaptation and optimization of the RHDUs to meet the emergent needs caused by the pandemic emphasizing the role of the expert application of noninvasive respiratory therapies in preventing intubation and ICU access.

Background: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS)., Methods: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO 2 , PaO 2 and NIV adherence (PROSPERO CRD42019132398)., Findings: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO 2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO 2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome., Interpretation: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks., Competing Interests: Competing interests: ML has no conflict of interest to declare related to the present work. He received speaker fees from Air Liquide Medical System, and Sefam, and non-financial support from Nomics outside the context of the submitted work. He received a salary from Air Liquide Medical System as a medical trainer. A Léotard has no conflict of interest to declare related to the present work. JC Borel is salaried by AGIR à dom, a home-care provider. JL Pépin and his department has received research support and personal fees from Philips Respironics, Sefam, Fisher and Paykel, and ResMed. JLP is supported by the French National Research Agency in the framework of the "Investissements d’avenir” program (ANR-15-IDEX-02) and the “e-health and integrated care and trajectories medicine and MIAI artificial intelligence” Chairs of excellence from the Grenoble Alpes University Foundation. This work has been partially supported by MIAI @ Grenoble Alpes (ANR-19-P3IA-0003). M Dreher has received speaking and advisor fees from companies in the field of mechanical ventilation; in addition, his study group received an open research grant from ResMed. JH Storre reports grants and personal fees for lectures from Heinen und Löwenstein and VitalAire, grants, personal fees for lectures and non-financial support for meeting attendance from Vivisol GmbH, grants from Weinmann Deutschland, personal fees for consultancy/advisory board work from Breas Medical AB regarding the submitted work; personal fees for consultancy and lectures, and non-financial support for meeting attendance from Boehringer Ingelheim Pharma, personal fees for consultancy and lectures from SenTec AG, Keller Medical GmbH, Linde Deutschland and Santis GmbH, outside the submitted work. M Patout reports personal fees from Resmed, Philips Respironics, grants and non-financial support from Fisher & Paykel, non-financial support and personal fees from Asten, research grants from B& D Electromedical and Fisher & Paykel, personal fees and non-financial support from Chiesi outside the submitted work. GC Funk received speaker fees from Draeger and Getinge. PJ Wijkstra reports grants and personal fees from Philips, grants and personal fees from RESMED, grants from Vital Air, grants from VIVISOL, grants from Goedegebuure, personal fees from Synapse, personal fees from Bresotec, outside the submitted work., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated with OSA might be age dependent. Objectives: To evaluate the association of OSA with the aging process and to determine whether this association is maintained across different age groups. Methods: This was an observational, prospective study including 599 patients with suspected OSA. Five hallmarks of aging were evaluated: alteration of cellular communication (serum CRP [C-reactive protein] concentration), deregulation of nutrient sensing (insulin resistance), telomere attrition (leukocyte telomeric length), mitochondrial dysfunction (leukocyte mitochondrial DNA copy number), and genomic instability (urinary 8-hydroxy-2-deoxyguanosine concentration). For age-stratified analyses, subjects were divided into four groups according to the apnea-hypopnea index (AHI) and the median age (50 yr): young patients without OSA (age < 50 yr old, AHI < 15 events/h), young patients with OSA (age < 50 yr old, AHI ⩾ 15 events/h), older patients without OSA (age ⩾ 50 yr old, AHI < 15 events/h), and older patients with OSA (age ⩾ 50 yr old, AHI ⩾ 15 events/h). Results: A dose-response relationship was found between the AHI, arousal index, and time during the night spent with an oxygen saturation less than 90% and the following hallmarks: alteration of cellular communication, deregulation of nutrient sensing, mitochondrial dysfunction, and genomic instability. Considering age-stratified analyses, OSA was associated with an increase in several hallmarks of aging in young patients, but no significant association of OSA was identified in older patients. Conclusions: In subjects under 50 years of age, OSA is associated with an increase in specific hallmarks of aging, independent of several known confounding factors.

Background: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE., Methods: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3-6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP., Results: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96-2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07-15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2-11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05-1.02; p=0.053)., Conclusions: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events., (Copyright © 2021. Publicado por Elsevier España, S.L.U.)

Introduction: Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension., Methods: The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up., Results: Patients were followed up within 59 months [interquartile range (IQR): 44-70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [-3.9 mmHg; 95% confidence interval (CI): -8.1 to 0.3] and diastolic pressure (-3.5 mmHg [95% [CI]: -6.4-0.5]), with a higher magnitude during the night (-5.5 and -4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01)., Conclusion: Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)