The Effect of Sleep Apnea on Cardiovascular Events in Different Acute Coronary Syndrome Phenotypes.

Rationale: Obstructive sleep apnea (OSA) is associated with increased cardiovascular disease (CVD) risk. Conversely, OSA has not been shown to increase recurrent cardiovascular events in patients with acute coronary syndrome (ACS). This lack of homogeneity could suggest that the deleterious effect of OSA and its contribution to CVD could depend on specific patient profiles.Objectives: To evaluate the effect of OSA on cardiovascular risk for patients with different ACS phenotypes.Methods:Post hoc analysis of the ISAACC (Continuous Positive Airway Pressure in Patients with ACS and OSA) study, including 1,701 patients admitted for ACS (NCT01335087). To evaluate the presence of OSA (apnea-hypopnea index ≥ 15 events · h-1), all patients underwent polygraphy. Patients were followed up for a minimum period of 1 year. We performed nonsupervised clustering using latent class analysis to identify subgroups of patients on the basis of 12 clinical factors associated with cardiovascular risk. The effect of OSA on recurrent cardiovascular event risk was evaluated for each phenotype identified.Measurements and Main Results: Two phenotypes were identified: patients without previous heart disease and without previous ACS ("no-previous-CVD" phenotype; 81%) and patients with previous heart disease and previous ACS ("previous-CVD" phenotype; 19%). The median (interquartile range) at follow-up was 2.67 (3.8) years. For the no-previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio (95% confidence interval) of 1.54 (1.06-2.24; P value = 0.02), whereas for the previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio of 0.69 (0.46-1.04; P value = 0.08).Conclusions: For patients with ACS and a specific phenotype, OSA is associated with an increased risk of recurrent cardiovascular events. These patients are mainly characterized by no previous heart disease and admission for a first ACS occurrence.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study.

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/m2 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.

Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

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.

Primary versus Specialist Care for Obstructive Sleep Apnea: A Systematic Review and Individual-Participant Data-Level Meta-Analysis.

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.

Long-Term Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients with Acute Coronary Syndrome: A Clinical Trial.

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/m2, 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).

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

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 (SaO2), average duration of events and percentage of time with SaO2 < 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 SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 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.

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

Reorganizing the respiratory high dependency unit for pandemics.

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.

Weight Loss Interventions as Treatment of Obesity Hypoventilation Syndrome. A Systematic Review.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Weight loss is an important component of management based on clinical rationale, but the evidence supporting weight loss has not been summarized and the optimal approach has not been determined.Objectives: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. The panel asked, "Should a weight loss intervention be performed in patients with OHS?"Methods: Medline, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that assessed weight loss interventions in obese adults with confirmed OHS, suspected OHS, or hypercapnia. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: The search identified 2,994 articles. Six studies were selected, including two randomized trials and four nonrandomized studies without a comparator. Sample size ranged from 16 to 63 subjects. The studies found that a comprehensive weight loss program (including motivational counseling, dieting, and exercise) can reduce weight by 6% to 7% but confers no clinically significant effects compared with standard care. Bariatric surgery, on the other hand, is associated with more robust weight loss (15-64.6%, depending on the type of intervention), reduction of obstructive sleep apnea severity (18-44% reduction of the apnea-hypopnea index), and improvement in gas exchange (17-20% reduction in partial pressure of carbon dioxide in the arterial blood), ultimately leading to the resolution of OHS. Moreover, daytime sleepiness and pulmonary artery pressure also improve with significant weight loss. Bariatric surgery is associated with adverse effects in roughly one-fifth of patients, but serious adverse effects are very rare. The level of certainty in the estimated effects was very low for most outcomes.Conclusions: The guideline panel for which the systematic review was performed made a conditional (i.e., weak) recommendation suggesting a weight loss intervention for patients with OHS, targeting a sustained weight loss of 25% to 30% of actual body weight. This recommendation was based on very low-quality evidence. Although the weight loss target is based on the observation that greater weight loss is associated with better outcomes, there is a need for better-quality studies to ascertain the degree of weight loss necessary to achieve improvement in clinically relevant outcomes in patients with OHS.

The Role of Positive Airway Pressure Therapy in Adults with Obesity Hypoventilation Syndrome. A Systematic Review and Meta-Analysis.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable complication of severe obesity. Although weight loss is an accepted component of management, it is difficult to achieve and sustain the degree of weight loss necessary to reverse OHS. As such, positive airway pressure (PAP) during sleep has become the cornerstone therapy for most patients with OHS. However, the value of PAP therapy remains uncertain.Objective: To perform a systematic review to determine whether adults with OHS should be treated with PAP therapy or not.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared PAP therapy (i.e., continuous PAP or noninvasive ventilation) to no PAP therapy in patients with OHS. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence.Results: The search identified 2,994 unique articles. The full text of 56 articles was reviewed, and 25 studies were selected, including 3 randomized trials, 12 nonrandomized comparative studies, and 10 randomized and nonrandomized studies without a comparator group. Sample size ranged from 21 to 1,527 patients. PAP was associated with increased resolution of OHS and improvements in mortality, gas exchange, daytime sleepiness, sleep quality, quality of life, and emergency department visits. Nearly half of patients experienced trivial adverse effects related to PAP therapy. Certainty in the estimated effects was low or very low for most outcomes.Conclusions: The panel made a conditional (i.e., weak) recommendation that PAP therapy during sleep be offered to patients with OHS to improve outcomes. This recommendation was based on very low-quality evidence.

Intra- and Inter-Physician Agreement in Therapeutic Decision for Sleep Apnea Syndrome.

BACKGROUND: Large variation in diagnostic procedures and treatment recommendations may hinder the management of obstructive sleep apnea (OSA) and also compromise correct interpretation of the results of multicenter clinical trials, especially in subjects with non-severe OSA. The aim of this study was to analyze the therapeutic decision-making between different sleep physicians in patients with AHI<40events/h. METHODS: Six experienced senior sleep specialists from different sleep centers of Spain were asked to make a therapeutic decision (CPAP treatment) based on anonymized recordings of patients with suspected OSA that has previously performed a sleep study. The clinical data was shown in an online database and included anthropometric features, clinical questionnaires, comorbidities, physical examination and sleep study results. Intra- and inter-observer decision-making were analyzed by the Fleiss' Kappa statistics (Kappa). RESULTS: A total of 720 medical decisions were taken to analyze the agreement between sleep professionals. Overall intra-observer evaluation reliability was almost perfect (Kappa=0.83, 95% CI, 0.75-0.90, p<0.001). However, overall inter-observer concordance decreased to moderate agreement (Kappa=0.46, 95% CI, 0.42-0.51, p<0.001). Nevertheless, it was especially low when considering AHI<15events/h. CONCLUSIONS: This study demonstrates a good intra-observer concordance in the therapeutic decision-making of different sleep physicians treating patients with low/moderate OSA. However, when analyzing inter-observer agreement the results were considerably worse. These findings underline the importance of developing improved consensus management protocols.

The Effect of Hospital Discharge with Empiric Noninvasive Ventilation on Mortality in Hospitalized Patients with Obesity Hypoventilation Syndrome. An Individual Patient Data Meta-Analysis.

Rationale: Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration).Objectives: An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out.Methods: A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality.Results: The literature search identified 2,994 articles. There were no randomized trials. Ten studies met a priori study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low.Conclusions: Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.

Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.

BACKGROUND: Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. METHODS: We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24-72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov, NCT01335087 and is now closed. FINDINGS: Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50-5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68-1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76-1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. INTERPRETATION: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. FUNDING: ResMed (Australia), Fondo de Investigación Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Noninvasive Ventilation versus CPAP as Initial Treatment of Obesity Hypoventilation Syndrome.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Treatment consists of weight loss and positive airway pressure (PAP) therapy. However, the preferred mode of PAP is uncertain.Objectives: To perform a systematic review to determine whether PAP therapy should be initiated as noninvasive ventilation (NIV) or continuous PAP (CPAP) in ambulatory patients with OHS.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared initial treatment with NIV to CPAP in OHS. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of evidence.Results: The search identified 2,994 potentially relevant articles, the full text of 21 articles was reviewed, and five articles were selected. The five articles included three randomized trials (one reported as two articles) and an observational study. The sample size ranged from 36 to 225 subjects. The evidence showed no differences in mortality, cardiovascular events, and healthcare resource use between patients with OHS treated with NIV or CPAP. Both PAP modalities were similarly effective in improving gas exchange, the need for supplemental oxygen, daytime sleepiness, sleep quality, quality of life, dyspnea, and sleep-disordered breathing. There was also no significant difference in adherence to NIV or CPAP therapy. Certainty in the estimated effects was low or very low for some outcomes. Therefore, the conditional recommendation was based on very low-quality evidence.Conclusions: The panel made a conditional (i.e., weak) recommendation that CPAP rather than NIV be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea (OSA). The effectiveness of CPAP is similar to that of NIV, but NIV is more costly and requires more resources than CPAP. Given that approximately 70% of patients with OHS have coexistent severe OSA, this recommendation applies to the great majority of patients with stable OHS, but it should not be extrapolated to patients with OHS without severe OSA. Patients of advanced age, with poor lung function, or with greater or recent acute ventilatory failure may not respond adequately to CPAP.

Prevalence, Characteristics, and Association of Obstructive Sleep Apnea with Blood Pressure Control in Patients with Resistant Hypertension.

Rationale: Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited.Objectives: The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control.Methods: We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants.Results: In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index ≥ 5 events/h); 31.7% (95% CI, 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant.Conclusions: The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.Clinical trial registered with www.clinicaltrials.gov (NCT03002558).

Biomarker panel in sleep apnea patients after an acute coronary event.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. METHODS: Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. RESULTS: Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. CONCLUSIONS: The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. CLINICAL TRIAL REGISTRATION: NCT01335087 (clinicaltrials.gov).

Daytime sleepiness and polysomnography in obstructive sleep apnea patients.

BACKGROUND: Excessive daytime sleepiness (EDS) is the major complaint in subjects with obstructive sleep apnea syndrome (OSAS). However, EDS is not universally present in all patients with OSAS. The mechanisms explaining why some patients with OSAS complain of EDS whereas others do not are unknown. OBJECTIVE: To investigate polysomnographic determinants of excessive daytime sleepiness (EDS) in a large multicenter cohort of patients with obstructive sleep apnea (OSAS). METHODS: All consecutive patients with an apnea-hypopnea index greater than 5h(-1) who were evaluated between 2003 and 2005. EDS was assessed using the Epworth Sleepiness Scale (ESS), and patients were considered to have EDS if the ESS was >10. RESULTS: A total of 1649 patients with EDS ((mean [+/-SD] Epworth 15+/-3) and 1233 without EDS (Epworth 7+/-3) were studied. Patients with EDS were slightly younger than patients without EDS (51+/-12 vs 54+/-13 years, p<0.0001), had longer total sleep time (p<0.007), shorter sleep latency (p<0001), greater sleep efficiency (p<0.0001) and less NREM sleep in stages 1 and 2 (p<0.007) than those without EDS. Furthermore, patients with EDS had slightly higher AHI (p<0.005) and arousal index (p<0.001) and lower nadir oxygen saturation (p<0.01). CONCLUSIONS: Patients with OSAS and EDS are characterized by longer sleep duration and increased slow wave sleep compared to those without EDS. Although patients with EDS showed a mild worsening of respiratory disturbance and sleep fragmentation, these results suggest that sleep apnea and sleep disruption are not the primary determinants of EDS in all of these patients.

[Differences in clinical and polysomnographic variables between male and female patients with sleep apnea-hypopnea syndrome]. / Influencia del sexo en las variables clínicas y polisomnográficas del síndrome de apneas del sueño.

OBJECTIVE: The aim of this study was to compare the clinical, anthropometric, and polysomnographic characteristics of a broad group of patients with sleep apnea-hypopnea syndrome according to sex. PATIENTS AND METHODS: The study, conducted in 6 Spanish university hospitals, included consecutive patients attended from 2003 through 2005 with an apnea-hypopnea index greater than 5. Groups were formed according to sex and then stratified into age subgroups of younger (< or = 45 years) and older patients (> 45 years) for further comparison. RESULTS: The study included 2464 men and 424 women. Women were older (mean [SD] age, 56 [12] years vs 51 [12] years), weighed more (body mass index, 31 [6] kg/m(2) vs 30 [5] kg/m2), and had a larger hip circumference (119 [15] cm vs 111 [12] cm) and smaller neck circumference (38 [3] cm vs 42 [9] cm) than men (P< .001 in all cases). The degree of daytime sleepiness (Epworth scale) and the apnea-hypopnea index were similar in both groups, although women had a longer sleep latency (23 [28] minutes vs 27 [32] minutes; P< .004) and a higher mean oxygen saturation (92% [4%] vs 91% [5%]) and minimum oxygen saturation (78% [11%] vs 75% [12%]; P< .0001) than men. On stratification by age, only weight differences between men and women were observed in the younger group whereas the older group also showed differences in oxygen saturation during sleep. CONCLUSIONS: Women with sleep apnea-hypopnea are more overweight than men and tend to seek medical attention at an older age. The clinical and polysomnographic variables were generally similar for men and womenthe only differences were that sleep latency was longer and hypoxemia during sleep was more accentuated in women.

Lung function impairment is not associated with the severity of acute coronary syndrome but is associated with a shorter stay in the coronary care unit.

BACKGROUND: Previous population-based studies have suggested that lung function impairment (LFI) could be associated with an increase in the mortality of cardiovascular events. METHODS: We evaluated the association between LFI and the severity and short-term prognosis of acute coronary syndrome (ACS). LFI was established through presence of a forced expiratory volume in one second (FEV1) and/or a forced vital capacity (FVC) less than 80% of predicted. RESULTS: Seventy-one LFI subjects (61.45±10.70 years, 83.10% males) and 247 non-LFI subjects (58.98±11.18 years, 80.57% males) with ACS were included. Subjects with LFI exhibited a higher prevalence of systemic hypertension (57.75% vs. 40.89%, P=0.02) and tobacco exposure (28.50±26.67 vs. 18.21±19.83 pack-years, P=0.007). No significant differences between groups were found regarding the severity of ACS (ejection fraction, Killip class, number of affected vessels, and peak plasma troponin). However, in comparison to non-LFI subjects, a significantly shorter length of stay in the coronary care unit (CCU) was observed in the LFI group (1.83±1.10 vs. 2.24±1.21 days, P=0.01) and this was even shorter in subjects with obstructive LFI (1.62±1.17 days, P=0.009). When considering obstructive sleep apnea (OSA), an interaction with length of stay was found, revealing that OSA subjects with obstructive LFI had the shortest length of stay in the CCU (0.60±0.89 days, P=0.05) also in comparison to non-LFI. CONCLUSIONS: This study indicates a possible association between LFI and a shorter length of stay in the CCU but does not show a significant association with ACS severity.