Is the time below 90% of SpO2 during sleep (T90%) a metric of good health? A longitudinal analysis of two cohorts.

BACKGROUND: Novel wireless-based technologies can easily record pulse oximetry at home. One of the main parameters that are recorded in sleep studies is the time under 90% of SpO2 (T90%) and the oxygen desaturation index 3% (ODI-3%). We assessed the association of T90% and/or ODI-3% in two different scenarios (a community-based study and a clinical setting) with all-cause mortality (primary outcome). METHODS: We included all individuals from the Sleep Heart Health Study (SHHS, community-based cohort) and Santiago Obstructive Sleep Apnea (SantOSA, clinical cohort) with complete data at baseline and follow-up. Two measures of hypoxemia (T90% and ODI-3%) were our primary exposures. The adjusted hazard ratios (HRs) per standard deviation (pSD) between T90% and incident all-cause mortality (primary outcome) were determined by adjusted Cox regression models. In the secondary analysis, to assess whether T90% varies across clinical factors, anthropometrics, abdominal obesity, metabolic rate, and SpO2, we conducted linear regression models. Incremental changes in R2 were conducted to test the hypothesis. RESULTS: A total of 4323 (56% male, median 64 years old, follow-up: 12 years, 23% events) and 1345 (77% male, median 55 years old, follow-up: 6 years, 11.6% events) patients were included in SHHS and SantOSA, respectively. Every 1 SD increase in T90% was associated with an adjusted HR of 1.18 [95% CI: 1.10-1.26] (p value < 0.001) in SHHS and HR 1.34 [95% CI: 1.04-1.71] (p value = 0.021) for all-cause mortality in SantOSA. Conversely, ODI-3% was not associated with worse outcomes. R2 explains 62% of the variability in T90%. The main contributors were baseline-mean change in SpO2, baseline SpO2, respiratory events, and age. CONCLUSION: The findings suggest that T90% may be an important marker of wellness in clinical and community-based scenarios. Although this nonspecific metric varies across the populations, ventilatory changes during sleep rather than other physiological or comorbidity variables explain their variability.

Association between Acute Respiratory Distress Syndrome Due to COVID-19 and Long-Term Sleep and Circadian Sleep-Wake Disorders.

Current studies agree on the impact of sleep and circadian rest-activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest-activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest-activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest-activity rhythm between four and twelve months or between the groups.

The U-Shaped Association between Sleep Duration, All-Cause Mortality and Cardiovascular Risk in a Hispanic/Latino Clinically Based Cohort.

Sleep is essential for life, and inappropriate sleep duration patterns may lead to chronic consequences regarding human health. Several studies have confirmed the presence of a U-shaped association between sleep duration and mortality. Moreover, many consequences related to cardiometabolic aspects have been suggested in patients with abnormal sleep durations. In this study, we analyzed the associations between sleep duration, total sleep time (TST), the risk of all-cause mortality, and 10-year cardiovascular risk in a cohort of patients at a sleep medicine center in Santiago, Chile. We conducted a prospective cohort study of patients (SantOSA). A short TST was defined as ≤6 h, a normal TST as 6 to 9 h, and a long TST as ≥9 h. Adjusted hazard ratios (aHRs) for all-cause mortality were calculated. A cross-sectional analysis between TST and 10-year cardiovascular risk (calculated using the Framingham 2008 formula) was determined using logistic regression models. A total of 1385 subjects were included in the results (78% male; median age: 53, interquartile range (IQR): 42-64 years; median BMI: 29.5, IQR: 16.7-33.1). A total of 333 subjects (24%) reported short TSTs, 938 (67.7%) reported normal TSTs, and 114 (8.3%) reported long TSTs. In the fully adjusted model, the association remained significant for short (aHR: 2.51 (1.48-4.25); p-value = 0.01) and long TSTs (aHR: 3.97 (1.53-10.29); p-value = 0.04). Finally, a U-shaped association was found between short and long TSTs, with an increase in cardiovascular risk at 10 years. Compared with normal TSTs, short (≤6 h) and long (≥9 h) TSTs were significantly associated with all-cause mortality and increased 10-year cardiovascular risk.

Clinical Application of the Multicomponent Grading System for Sleep Apnea Classification and Incident Cardiovascular Mortality.

Objective To evaluate the clinical utility of the Baveno classification in predicting incident cardiovascular mortality after five years of follow-up in a clinic-based cohort of patients with obstructive sleep apnea (OSA). Materials and Methods We evaluated the reproducibility of the Baveno classification using data from the Santiago Obstructive Sleep Apnea (SantOSA) study. The groups were labeled Baveno A (minor symptoms and comorbidities), B (severe symptoms and minor comorbidities), C (minor symptoms and severe comorbidities), and D (severe symptoms and comorbidities). Within-group comparisons were performed using analysis of variance (ANOVA) and post hoc tests. The associations between groups and incident cardiovascular mortality were determined through the Mantel-Cox and Cox proportional hazard ratios (HRs) adjusted by covariables. Results A total of 1,300 OSA patients were included (Baveno A: 27.7%; B: 28%; C: 16.8%; and D: 27.5%). The follow-up was of 5.4 years. Compared to Baveno A, the fully-adjusted risk of cardiovascular mortality with Baveno B presented an HR of 1.38 (95% confidence interval [95%CI]: 0.14-13.5; p = 0.78); with Baveno C, it was of 1.71 (95%CI: 0.18-16.2; p = 0.63); and, with Baveno D, of 1.04 (95%CI: 0.12-9.2; p = 0.98). We found no interactions involving Baveno group, sex and OSA severity. Discussion Among OSA patients, the Baveno classification can describe different subgroups. However, its utility in identifying incident cardiovascular mortality is unclear. Long-term follow-up studies and the inclusion of demographic variables in the classification could improve its ability to detect a high-risk phenotype associated with cardiovascular mortality. Conclusion The Baveno classification serves as a valuable method for categorizing varying groups of patients afflicted with OSA. Nevertheless, its precision in identifying occurrence of cardiovascular mortality is still unclear.

Undiagnosed sleep disorder breathing as a risk factor for critical COVID-19 and pulmonary consequences at the midterm follow-up.

INTRODUCTION: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB). OBJECTIVES: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis. METHODS: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed. RESULTS: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT. CONCLUSION: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm. STUDY REGISTER: ISRCTN16865246.

Fenotipos clínicos en el síndrome de apnea obstructiva del sueño / Clinical phenotypes in obstructive sleep apnea

El síndrome de apnea e hipopnea obstructiva del sueño se caracteriza por episodios repetitivos de obstrucción de vía aérea superior y es reconocida cada vez más, como un trastorno heterogéneo y complejo, proponiéndose múltiples fenotipos en base a su mecanismo patogénico, alteraciones polisomnográficas y la presentación clínica. El fenotipo clínico se enfoca en identificar características de un paciente basándose en signos, síntomas, antropometría, comorbilidades, medidas fisiológicas, anatómicas o respuesta al tratamiento. Al ser una enfermedad sub diagnosticada, de alta prevalencia y que produce elevada morbi-mortalidad, se debe estar atento a la pesquisa precoz y en las poblaciones de riesgo. Su diagnóstico se basa en el índice de apnea-hipopnea (IAH) y se requiere un IAH •5 eventos/hora para confirmar el diagnóstico. Sin embargo, cada vez hay más evidencia que el IAH por sí solo es insuficiente para comprender la presentación clínica, respuesta al tratamiento, calidad de vida y mortalidad de los pacientes con apnea del sueño. El fenotipo clínico puede servir de este modo, para entender mejor las diferentes formas de presentación teniendo como finalidad la medicina personalizada con el objetivo de favorecer la conducta terapéutica individualizada. El objetivo de esta revisión es abordar los fenotipos clínicos y proponer una huella digital en los pacientes con apnea del sueño

Obstructive sleep apnea and hypopnea syndrome is characterized by repetitive episodes of upper airway obstruction and is increasingly recognized as a heterogeneous and complex disorder, proposing multiple phenotypes based on its pathogenic mechanism, polysomnographic alterations, and clinical presentation. The clinical phenotype focuses on identifying a patient's characteristics based on signs, symptoms, anthropometry, comorbidities, physiological, anatomical measures or response to treatment. As it is an underdiagnosed disease of high prevalence associated to high morbidity and mortality, we must be alert to early screening and risk populations. Diagnosis is based on the apnea-hypopnea index (AHI) AHI •5 events/hour is required to confirm it, however, there is increasing evidence that AHI alone is insufficient to understand the clinical presentation, the response to treatment, the quality of life and the mortality of patients with sleep apnea. In this way, the clinical phenotype can serve to better understand the different forms of presentation and looks for a personalized medicine that favors an individualized therapeutic behavior. The aim of this review is to address clinical phenotypes and propose a fingerprint in patients with sleep apnea

Telemedicine interventions for CPAP adherence in obstructive sleep apnea patients: Systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the preferred therapy in patients with obstructive sleep apnea (OSA). However, data suggests treatment adherence is low. In recent years, telemedicine-based intervention (TM) has been evaluated to increase adherence. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we evaluated the efficacy of TM on CPAP adherence in patients with OSA. Two independent reviewers explored five databases; the risk of bias (RoB) was evaluated using the Cochrane tool. Outcomes were defined as the mean difference (MD) in CPAP use per night and the proportion of patients with increased CPAP adherence of ≥4 h/night. The meta-analysis was conducted following the DerSimonian-Laird method, and the certainty of the evidence was rated according to GRADE. We included 16 RCTs including 3039 participants. The RoB was low in 12/16 studies. TM was associated with an increase in CPAP adherence of 29.2 min/night, I2 =75% (p < 0.01), and CPAP adherence ≧4 h/night, RR: 1.09 (1.02-1.17), I2 =22%. Subgroup analyses reported better results between three and 6 months, in the sleepy subgroup. Finally, based on the results obtained in this systematic review, there is favorable evidence regarding the treatment with TM in patients with OSA using CPAP. REVIEW REGISTRATION NUMBER: CRD42020165367.

A Validation Study of Four Different Cluster Analyses of OSA and the Incidence of Cardiovascular Mortality in a Hispanic Population.

BACKGROUND: Previous studies reported a strong association between sleepiness-related symptoms and comorbidities with poor cardiovascular outcomes among patients with moderate to severe OSA (msOSA). However, the validation of these associations in the Hispanic population from South America and the ability to predict incident cardiovascular disease remain unclear. RESEARCH QUESTION: In Hispanic patients with msOSA, are four different cluster analyses reproducible and able to predict incident cardiovascular mortality? STUDY DESIGN AND METHODS: Using the SantOSA cohort, we reproduced four cluster analyses (Sleep Heart Health Study [SHHS], Icelandic Sleep Apnea Cohort [ISAC], Sleep Apnea Cardiovascular Endpoints [SAVE], and The Institute de Recherche en Sante Respiratoire des Pays de la Loire [IRSR] cohorts) following a cluster analysis similar to each training dataset. The incidence of cardiovascular mortality was constructed using a Kaplan-Meier (log-rank) model, and Cox proportional hazards models were adjusted by confounders. RESULTS: Among 780 patients with msOSA in our cohort, two previous cluster analyses (SHHS and ISAC) were reproducible. The SAVE and IRSR cluster analyses were not reproducible in our sample. We identified the following subtypes for SHHS: "minimally symptomatic," "disturbed sleep," "moderate sleepiness," and "severe sleepiness." For ISAC, three different subtypes ("minimally symptomatic," "disturbed sleep," and "excessive sleepiness") were similar to the original dataset. Compared with "minimally symptomatic," we found a significant association between "excessive sleepiness" and cardiovascular mortality after 5 years of follow-up in SantOSA, hazard ratio (HR), 5.47; 95% CI, 1.74-8.29; P < .01; and HR, 3.23; 95% CI, 1.21-8.63; P = .02, using the SHHS and ISAC cluster analyses, respectively. INTERPRETATION: Among patients with msOSA, a symptom-based approach can validate different OSA patient subtypes, and those with excessive sleepiness have an increased risk of incident cardiovascular mortality in the Hispanic population from South America.

Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): Systematic review and meta-analysis.

Approximately 70-85% of patients with resistant hypertension (RH) report obstructive sleep apnea (OSA). However, whether therapy with continuous positive airway pressure (CPAP) improves blood pressure (BP) in this population is not clear. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy of CPAP in patients with OSA and RH. Two reviewers performed the literature search, risk of bias analysis, and data extraction. The pooled data were analyzed in a meta-analysis using the DerSimonian-Laird method. We calculated the mean difference (MD) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured at 24 h and in the daytime and nighttime. We also evaluated changes in aortic stiffness and aldosterone excretion. A total of 10 RCTs and 606 participants were included. CPAP was associated with changes in 24-h SBP (-5.06 mmHg; CI, -7.98, -2.13), 24-h DBP (-4.21 mmHg; CI, -6.5, -1.93), daytime SBP (-2.34 mmHg; CI, -6.94, +2.27), daytime DBP (-2.14 mmHg; CI, -4.96, -0.67), nighttime SBP (-4.15 mmHg; CI, -7.01, -1.29), and nighttime DBP (-1.95 mmHg; CI, -3.32, -0.57). We found no benefit for aortic stiffness, but it did lead to a mild reduction in aldosterone secretion. CPAP therapy improved BP, especially nighttime BP, in this population.

Risk of mortality among patients with moderate to severe obstructive sleep apnea and diabetes mellitus: results from the SantOSA cohort.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) and comorbid diabetes mellitus (DM) are reported to have an increased risk of cardiovascular (CV) outcomes; however, data on CV mortality are scant. AIM: This study aimed to evaluate if patients with comorbid OSA and DM have an increased risk of CV mortality that is higher than the two diseases in isolation. METHODS: In this prospective cohort study, we included patients referred for a sleep study with and without DM at baseline. We developed four study groups as follows: group 1 (reference group), OSA (-) DM (-); group 2, OSA (-) DM (+); group 3, OSA (+) DM (-); group 4, OSA (+) DM (+). Intergroup differences were evaluated using the t test and χ2 test, and multivariate analysis was performed using logistic regression. The incidence rates of CV mortality were calculated using the Kaplan-Meier (log-rank) model, and adjusted HRs were calculated using the Cox regression model. RESULTS: A total of 1447 patients were included in the analysis-group 1: 441 participants; group 2: 141 participants; group 3: 736 participants; group 4: 151 participants. The mean follow-up was 5 years. The association between OSA + DM showed an independent risk of incident CV mortality (HR 2.37, CI 1.16-4.82, p = 0.02) and an increased prevalence of coronary heart disease (OR 3.44, CI 1.73-5.59, p < 0.01). In addition, T90% was also associated with CV mortality. CONCLUSION: The coexistence of OSA + DM was associated with an independent risk of CV mortality. In addition, T90% was also associated with CV mortality.

Hypoxemic features of obstructive sleep apnea and the risk of mortality: a cluster analysis.

INTRODUCTION: Patients with moderate to severe obstructive sleep apnea (OSA) have an increased risk of cardiovascular comorbidities and mortality. Although different subtypes of OSA have been described, data about oximetric parameters and their suitability to identify a different phenotype are scant. In this study, we evaluate the association between moderate to severe OSA and oximetric parameters included in the home sleep apnea test (HSAT) and the risks of all-cause mortality, cardiovascular mortality, and cancer mortality. METHODS: Adult patients with moderate to severe OSA from a clinical cohort in Chile were included (SantOSA study). We developed a latent class analysis (LCA) incorporating oximetric measures commonly reported on HSAT. Differences between the groups were evaluated using ANOVA and the chi-squared test. Survival curves were constructed using a Kaplan-Meier (log-rank) model, and adjusted hazard ratios of mortality were calculated using a Cox regression model following a confounder analysis of cardiovascular comorbidities. RESULTS: A total of 889 patients were included in the analysis. LCA identified three different clusters: Cluster 1, "nonhypoxemic" (n = 591); cluster 2, "moderately hypoxemic" (n = 297); and cluster 3, "severely hypoxemic" (n = 115). The mean follow-up was 4.7 years. The hypoxemic groups showed an increased risk of cardiometabolic comorbidities and an independent risk of all-cause mortality (adjusted HR 1.67 (CI 1.0-2.64) p value = 0.027). The moderately hypoxemic group had an adjusted HR of 2.92 (CI 1.00-8.58), p value = 0.05, while the severely hypoxemic group had an adjusted HR of 2.55 (CI 1.08-6.02), p value = 0.031. For cardiovascular mortality, we found an HR of 2.03 (CI 0.50-8.136), p value = 0.31, and for cancer mortality, we found an HR of 5.75 (CI 1.03-32.17), p value = 0.042. CONCLUSION: Oximetric parameters are useful for describing a different phenotype with a high risk of mortality among patients with moderate to severe OSA, beyond the apnea-hypopnea index.

A clinic-based cluster analysis in patients with moderate-severe obstructive sleep apnea (OSA) in Chile.

RATIONALE: Patients commonly report differences in either clinical or symptomatic profiles, despite having the same severity of obstructive sleep apnea (OSA). OBJECTIVE: To identify clinical and symptomatic phenotypes and to evaluate cardiovascular mortality in each phenotype. METHODS: Data from 1370 participants (788 with moderate-severe OSA and 582 controls as a reference group) were extracted using the SantOSA database. Sixteen variables were analyzed using latent class analysis to define clinical subtypes. The association between subtypes and cardiovascular mortality was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Adjusted hazard ratios (HRs) with confidence intervals (CIs) were modified by cardiovascular confounders. RESULTS: The median observation period was 5.2 years. We found four clusters: cluster #1: symptomatic men with major comorbidities (n = 252); cluster #2: symptomatic women with comorbidities (n = 154); cluster #3: asymptomatic men with comorbidities (n = 143); and cluster #4: symptomatic young men without major comorbidities (n = 239). In cluster #1, mortality was 4.76% and was independently associated with age (HR 1.12; CI 1.07-1.17), type 2 diabetes mellitus (HR 3.37; CI 1.29-8.78) and coronary heart disease (HR 3.85; CI 1.27-11.56); in cluster #2, mortality was 3.89% and was independently associated with age (HR 1.12; CI 1.06-1.19) and the oxygen desaturation index (ODI, HR 1.02; CI 1.01-1.04); and in cluster #3, mortality was 3.49% (HR 3.50; CI 1.03-11.90) and was independently associated with age (HR 1.19; CI 1.10-1.29). In cluster #4, mortality was 1.25% and showed nonsignificant associations. CONCLUSION: In patients with moderate-severe OSA, we described four phenotypes of patients according to clinical features with different risks of cardiovascular mortality. STUDY REGISTER: ISRCTN62293645.

Clinical utility of oximetric parameters to identify a high-risk phenotype of moderate-severe Obstructive Sleep Apnea (OSA).

It is unclear if oximetric parameters, such as total time of SpO2  < 90%, (T90), oxygen desaturation index-3% (ODI), minimum SpO2 , are able to describe a high-risk subtype of cardiovascular (CV) comorbidities in patients with Obstructive sleep apnea (OSA) beyond the apnea-hypopnea index. OBJECTIVE: To analyzed oximetric variables in patients with moderate-severe OSA to assess their predictive value regarding as hypertension, type 2 diabetes mellitus (T2DM), coronary heart disease (CHD) and CV mortality. METHODS: Using data from SantOSA cohort, we develop receiver operating characteristic curve and area under the curve (AUC) for each parameter, defining the proposed cutoff point in a training set. Then, in a validation set with a 5 years follow-up, we evaluate the clinical differences between groups using the proposed cutoff. We also calculated adjusted Hazard Ratios (HR) of mortality using a Cox regression model. RESULTS: About 965 patients with moderate-severe OSA (525 in training and 440 in validation group) were included. The best AUC was achieved with T90 (AUC = 0.66) and ODI (AUC = 0.61). Proposed cutoffs of T90 were hypertension: 10%, T2DM: 20%, CHD: 15%, meanwhile, proposed cutoff of ODI was ≥ 30 ev for hypertension and T2DM. Regarding CV mortality, T90 ≥ 20% was independently associated with an adjusted HR 2.44 (CI, 1.21-4.94), P-value = 0.01, meanwhile, ODI ≥ 30 ev. reported and adjusted HR 1.59 (CI, 0.75-3.39), P-value = 0.22. CONCLUSION: In patients with moderate-severe OSA, oximetric parameters, especially T90 ≥ 20% remained a predictor of mortality after adjusting for a range of demographic and disease predictors.

Efficacy of CPAP for Improvements in Sleepiness, Cognition, Mood, and Quality of Life in Elderly Patients With OSA: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: OSA is found commonly in the elderly population (≥65 years old), and CPAP improves sleepiness and health-related quality of life (HRQoL) in the middle-aged population; however, data about its efficacy in elderly patients are unclear. The purpose of this study was to evaluate the efficacy of CPAP for sleepiness, HRQoL, mood, and cognition in elderly patients with OSA. RESEARCH QUESTION: In elderly patients (≥65 years old) with OSA, is CPAP, compared with usual care or sham CPAP, effective at improving sleepiness, HRQoL, mood, and neurocognitive function? STUDY DESIGN AND METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that included trials performed in elderly patients with OSA. As an intervention, we compared CPAP vs a control group. Two independent reviewers explored several databases; risk of bias (RoB) was evaluated with the Cochrane tool. Changes in sleepiness (Epworth Sleepiness Scale), HRQoL (Quebec Sleep Questionnaire), mood (Hospital Anxiety-Depression Scale), and neurocognitive tests after treatment were the outcomes. The meta-analysis was conducted according to the DerSimonian-Laird method, and the quality of evidence was rated according to the GRADE guidelines. RESULTS: A total of 4 randomized controlled trials (680 participants) were included. RoB was high for performance and detection bias. CPAP was associated with a 2.62-point improvement in the Epworth Sleepiness Scale (1.93 to 3.30; I2 = 52%). All domains of the Quebec Sleep Questionnaire were improved: hypersomnolence, 0.67 points (0.31 to 1.03; I2 = 75%); diurnal symptoms, -0.71 points (-0.98 to -0.44; I2 = 58%); nocturnal symptoms, 1.09 points (0.9 to 1.27; I2 = 9%); emotions, 0.45 points (0.30 to 0.61; I2 = 11%); and social interaction, 0.55 points (0.1 to 0.99; I2 = 82%). CPAP also improved the Hospital Anxiety-Depression Scale depression domain, and there were reports of a slight improvement in neurocognitive tests. The quality of evidence was low and very low for all outcomes. INTERPRETATION: Although CPAP therapy reportedly results in important clinical differences in sleepiness, HRQoL, and mood and a slight improvement in neurocognitive tests, concerns regarding the RoB and quality of the evidence do not support the benefit in all patients. TRIAL REGISTER: PROSPERO ID CRD42019146947.

Efficacy of continuous positive airway pressure (CPAP) in the prevention of cardiovascular events in patients with obstructive sleep apnea: Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) commonly occurs in patients with increased cardiovascular (CV) risk, and continuous positive airway pressure (CPAP) is the preferred therapy for these patients. The aim of this review was to evaluate the efficacy of CPAP for CV prevention in OSA patients. We conducted a systematic review of randomized controlled trials (RCTs). Two independent reviewers explored different databases and evaluated the risk of bias. Outcomes were defined as the relative risk (RR) of major CV events (MACEs), CV mortality, myocardial infarction, unstable angina, stroke, atrial fibrillation (Afrib) and heart failure. We performed both subgroup and meta-regression analyses by sleepiness status, adherence, and OSA severity. The certainty of evidence was rated according to GRADE. A total of 8 RCTs and 5817 participants were included. The results showed an RR of 0.87 (CI, 0.70-1.10) for MACEs, an RR of 0.94 (CI, 0.62-1.43) for CV mortality, an RR of 1.04 (CI, 0.79-1.37) for myocardial infarction, an RR of 1.05 (CI, 0.51-2.15) for unstable angina, an RR of 0.92 (CI, 0.68-1.23) for heart failure, an RR of 0.94 (CI, 0.71-1.26) for stroke, and an RR of 0.94 (CI, 0.54-1.64) for Afrib. Subgroup analysis and meta-regression revealed no effect on our proposed outcomes. Although there is no evidence that CPAP therapy improves CV outcomes, concerns regarding risk of bias, CPAP adherence, and the population included in each RCT may have reduced the strength of the findings to support the benefit in all patients, and future research exploring these relevant outcomes is needed. REVIEW REGISTER: PROSPERO CRD42019145803.

Chronic intermittent hypoxia in obstructive sleep apnea: a narrative review from pathophysiological pathways to a precision clinical approach.

Obstructive sleep apnea syndrome (OSAS) is a prevalent condition caused by dynamic upper airway collapse during sleep. The pathological impact and consequences are due to chronic intermittent hypoxia (CIH). Hypoxia increases the expression of several inflammatory stress markers and endothelial dysfunction. Recent studies suggest that patients with a similar AHI but with severe nocturnal hypoxia using oximetric parameters, such as the lowest saturation of oxygen during the night (min SaO2), percentage of total sleep time with oxygen saturation < 90% (T90) or the oxygen desaturation index (ODI-3%), commonly reported during the sleep study, are indicative of the increased expression of inflammatory markers due to severe nocturnal hypoxia and CIH during the night compared to subjects with moderate-severe OSAS without severe nocturnal hypoxia. The aim of this review is to describe physiological pathways involved in OSAS and their clinical consequences, focused in CIH and oximetric parameters showed in sleep study and their potential utility as inflammatory markers.

Differences in patients derived from otolaryngology and other specialties with sleep apnea.

BACKGROUND: Snoring is a main concern in patients who consult an otolaryngologist (ENT physicians) and patients who have cardiovascular comorbidities or excessive daytime sleepiness who usually consult with other specialists. The aim of this study was to describe the clinical differences in patients with obstructive sleep apnea (OSA) referred from ENT or other specialists. METHODS: A prospective study was carried out between June 2015 and July 2018 in a tertiary center. We included patients with suspected OSA referred by the Home Sleep Apnea Test (HSAT) from different specialties such as ENT or other specialties. The main outcome measures of our study were demographic characteristics, clinical characteristics, sleep questionnaire results and HSAT results between OSA patients referred from ENT or other specialists. We used a t-test and chi-squared test for analysis. The diagnostic accuracy of the sleep questionnaires was achieved using receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: A total of 481 patients were included. OSA was occurred in 82.4% of the subjects (90 in ENT and 306 in other specialties). Patients with OSA referred from other specialists were older than ENT patients (55 ± 13 vs 44 ± 12; p < 0.001), there was more obesity (IMC 31 ± 5.0 vs 28.7 ± 3.8; p < 0,001), a larger neck circumference (42.2 cm ± 3.7 vs 40.6 cm ± 3.0; p < 0.001) and more reported comorbidities (p < 0.001). ENT patients reported mild OSA (46% vs 31%, p = 0.015) and more positional apnea (62% vs 39%, p = 0.002). In this group, the STOP-BANG questionnaire showed an AUC 0.695 vs AUC 0.804, and for sensitivity, the best cutoff was 4 points. Patients referred from otorhinolaryngology are different from those referred from other specialties. Clinical evaluation and screening of OSA should be patient-centered according to these clinical findings.