Effect of Acute Intermittent CPAP Depressurization during Sleep in Obese Patients

Background

Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.

Methods

Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic (11.1 ± 0.6 cm H₂0) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.

Results

8/9 subjects tolerated CPAP withdrawal. The average AHI during CPAP-on and CPAP-off periods was 3.6 ± 0.6 and 15.8 ± 3.6 respectively (p<0.05). The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).

Conclusion

Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP.     

Socio-Economic Status: A Barrier to Access to Mandibular Advancement Device Therapy for Patients with Obstructive Sleep Apnea Syndrome in France

Background

Obstructive sleep apnea syndrome (OSAS) is a major public health problem which affects between 5 to 10% of the general population. OSAS is known to be associated with high rates of morbidity and mortality mainly due to cardiovascular diseases and traffic accidents. The burden of illness is high for the individual and society. There are 2 treatment options for OSAS, Continuous Positive Airway Pressure (CPAP) and Mandibular Advancement Device therapy (MAD). CPAP is known to be an effective but very constraining treatment. Patients are usually poorly adherent. MAD is a more recent treatment easier to use and consequently better tolerated, but MAD can only be prescribed to patients with satisfactory oral hygiene. Oral health constitutes a real issue particularly among underprivileged groups in France. Through this link, the question of whether low socio-economic status constitutes a barrier to access to care for patients with OSAS is raised.

Methods and Principal Findings

In a multicenter prospective cohort of 2822 consecutive OSAS patients in whom MAD has been proposed as an alternative to CPAP between May 15, 2007 and December 1st, 2014, we identified the factors that lead to a patient diagnosed with OSAS to be treated by MAD instead of CPAP. A logistic regression was performed using a stepwise forward procedure. The main outcome of the study was that treatment by MAD was significantly associated with both educational attainment, as determined by the age at which the patient left full-time education, ≥18 years compared with <18 (adjusted odds ratio (aOR): 1.64, 95% CI 1.23 to 2.20), and the patient''s occupational category. Executives and higher intellectual professions, intermediate professions, technicians, foremen and employees were significantly more likely to be treated by MAD than workers (aOR: 2.21, 95% CI 1.88 to 2.58; aOR: 1.74, 95% CI 1.15 to 2.63; aOR: 1.96, 95% CI 1.11 to 3.47, respectively).

Conclusions

Overall, these results suggest that low socio-economic status constitutes a barrier to access to MAD for patients with OSAS in France. MAD use in patients with OSAS highlights inequalities in health care access.     

Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives

1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design

Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting

Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients

Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions

Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes.

Measurements and Results

An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%).

Conclusions

The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.     

Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial

Objective

This study aimed to examine the effects of carbocysteine in OSAS patients.

Methods

A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group.

Results

The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18±4.28 vs. 6.82±3.66; P≤0.01), apnea-hypopnea index (55.34±25.03 vs. 47.56±27.32; P≤0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P≤0.01), and lowest oxygen saturation level (65.88±14.86 vs. 70.41±14.34; P≤0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71±0.15 vs. 0.66±0.15; P≤0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group.

Conclusions

Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02015598","term_id":"NCT02015598"}}NCT02015598     

Characterization of Sleep Breathing Pattern in Patients with Type 2 Diabetes: Sweet Sleep Study

Background

Although sleep apnea-hypopnea syndrome (SAHS) is highly prevalent in patients with type 2 diabetes (T2D), it is unknown whether or not subjects with and without T2D share the same sleep breathing pattern.

Methodology/Principal findings

A cross-sectional study in patients with SAHS according to the presence (n = 132) or not (n = 264) of T2D. Both groups were matched by age, gender, BMI, and waist and neck circumferences. A subgroup of 125 subjects was also matched by AHI. The exclusion criteria included chronic respiratory disease, alcohol abuse, use of sedatives, and heart failure. A higher apnea hypopnea index (AHI) was observed in T2D patients [32.2 (10.2–114.0) vs. 25.6 (10.2–123.4) events/hours; p = 0.002). When sleep events were evaluated separately, patients with T2D showed a significant increase in apnea events [8.4 (0.1–87.7) vs. 6.3 (0.0–105.6) e/h; p = 0.044), as well as a two-fold increase in the percentage of time spent with oxygen saturation <90% [15.7 (0.0–97.0) vs. 7.9 (0.0–95.6) %; <0.001)], higher rates of oxygen desaturation events, and also higher daily sleepiness [7.0 (0.0–21.0) vs. 5.0 (0.0–21.0); p = 0.006)] than subjects without T2D. Significant positive correlations between fasting plasma glucose and AHI, the apnea events, and CT90 were observed. Finally, multiple linear regression analyses showed that T2D was independently associated with AHI (R² = 0.217), the apnea index (R² = 0.194), CT90 (R² = 0.222), and desaturation events.

Conclusions/significance

T2D patients present a different pattern of sleep breathing than subject without diabetes. The most important differences are the severity of hypoxemia and the number of apneas whereas the incidence of hypopnea episodes is similar.     

A prospective cohort study of the long-term effects of CPAP on carotid artery intima-media thickness in Obstructive sleep apnea syndrome

Objective

To examine the long-term effect of CPAP on carotid artery intima-media thickness (IMT) in patients with Obstructive sleep apnea syndrome(OSAS).

Methods

A prospective observational study over 12 months at a teaching hospital on 50 patients newly diagnosed with OSAS who received CPAP or conservative treatment (CT). Carotid IMT was assessed with B-mode Doppler ultrasound from both carotid arteries using images of the far wall of the distal 10 mm of the common carotid arteries at baseline, 6 months and 12 months.

Measurements and results [mean (SE)]

Altogether 28 and 22 patients received CPAP and CT respectively without significant differences in age 48.8(1.8) vs 50.5(2.0)yrs, BMI 28.2(0.7) vs 28.0(1.2)kg/m2, ESS 13.1(0.7) vs 12.7(0.6), AHI 38(3) vs 39(3)/hr, arousal index 29(2) vs 29(2)/hr, minimum SaO₂ 75(2) vs 77(2)% and existing co-morbidities. CPAP usage was 4.6(0.3) and 4.7(0.4)hrs/night over 6 months and 1 year respectively. Carotid artery IMT at baseline, 6 months, and 12 months were 758(30), 721(20), and 705(20)micron for the CPAP group versus 760(30), 770(30), and 778(30)micron respectively for the CT group, p = 0.002.Among those free of cardiovascular disease(n = 24), the carotid artery IMT at baseline, 6 months and 12 months were 722(40), 691(40), and 659(30)micron for the CPAP group (n = 12) with usage 4.5(0.7) and 4.7(0.7) hrs/night over 6 months and 12 months whereas the IMT data for the CT group(n = 12) were 660(20), 685(10), and 690(20)micron respectively, p = 0.006.

Conclusions

Reduction of carotid artery IMT occurred mostly in the first 6 months and was sustained at 12 months in patients with reasonable CPAP compliance.     

Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease

Rationale

There is growing evidence that obstructive sleep apnea is associated with coronary artery disease. However, there are no data on the course of coronary stenosis after percutaneous coronary intervention in patients with obstructive sleep apnea.

Objectives

To determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.

Methods

78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea – Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 ± 3.1 months.

Main results

Angiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 ± 0.69 mm vs. 0.38 ± 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 ± 0.47 mm vs. 0.99 ± 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206).

Conclusion

In summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.     

Effect of Continuous Positive Airway Pressure on Adiponectin in Patients with Obstructive Sleep Apnea: A Meta-Analysis

Objective

Obstructive sleep apnea (OSA) has been suggested to be associated with low levels of adiponectin. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; however, previous studies assessing the effect of CPAP on adiponectin in patients with OSA yielded conflicting results. The present meta-analysis was performed to determine whether CPAP therapy could increase adiponectin levels.

Methods

Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before February 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum adiponectin was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy.

Results

Eleven studies involving 240 patients were included in this meta-analysis, including ten observational studies and one randomized controlled study. The meta-analysis showed that there was no change of adiponectin levels before and after CPAP treatment in OSA patients (SMD = 0.059, 95% confidence interval (CI) = −0.250 to 0.368, z = 0.37, p = 0.710). Subgroup analyses indicated that the results were not affected by age, baseline body mass index, severity of OSA, CPAP therapy duration, sample size and racial differences.

Conclusions

This meta-analysis suggested that CPAP therapy has no impact on adiponectin in OSA patients, without significant changes in body weight. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue.     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.     

Energy Types of Snoring Sounds in Patients with Obstructive Sleep Apnea Syndrome: A Preliminary Observation

Background

Annoying snore is the principle symptom and problem in obstructive sleep apnea syndrome (OSAS). However, investigation has been hampered by the complex snoring sound analyses.

Objective

This study was aimed to investigate the energy types of the full-night snoring sounds in patients with OSAS.

Patients and Method

Twenty male OSAS patients underwent snoring sound recording throughout 6 hours of in-lab overnight polysomnogragphy. Snoring sounds were processed and analyzed by a new sound analytic program, named as Snore Map®. We transformed the 6-hour snoring sound power spectra into the energy spectrum and classified it as snore map type 1 (monosyllabic low-frequency snore), type 2 (duplex low-&mid-frequency snore), type 3 (duplex low- & high-frequency snore), and type 4 (triplex low-, mid-, & high-frequency snore). The interrator and test-retest reliabilities of snore map typing were assessed. The snore map types and their associations among demographic data, subjective snoring questionnaires, and polysomnographic parameters were explored.

Results

The interrator reliability of snore map typing were almost perfect (κ = 0.87) and the test-retest reliability was high (r = 0.71). The snore map type was proportional to the body mass index (r = 0.63, P = 0.003) and neck circumference (r = 0.52, P = 0.018). Snore map types were unrelated to subjective snoring questionnaire scores (All P>0.05). After adjustment for body mass index and neck circumference, snore map type 3–4 was significantly associated with severity of OSAS (r = 0.52, P = 0.026).

Conclusions

Snore map typing of a full-night energy spectrum is feasible and reliable. The presence of a higher snore map type is a warning sign of severe OSAS and indicated priority OSAS management. Future studies are warranted to evaluate whether snore map type can be used to discriminate OSAS from primary snoring and whether it is affected by OSAS management.     

Obstructive Sleep Apnoea Syndrome,Endothelial Function and Markers of Endothelialization. Changes after CPAP

Study objectives

This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy.

Design

Observational study, before and after CPAP therapy.

Setting and Patients

We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process.

Measurements and results

After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together.

Conclusions

CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.     

Symptoms of Obstructive Sleep Apnea,Gastroesophageal Reflux and the Risk of Barrett’s Esophagus in a Population-Based Case-Control Study

Background

Gastroesophageal reflux is overrepresented in people with obstructive sleep apnea (OSA) and it has been suggested that OSA worsens gastroesophageal reflux symptoms. Aggravated reflux might lead to an increased risk of Barrett’s esophagus.

Aim

To assess the association between sleep apnea symptoms and Barrett’s esophagus.

Methods

Included in a case-control study in Brisbane, Australia were 237 patients with histologically confirmed Barrett’s esophagus and 247 population controls. The controls were randomly selected from the electoral roll and frequency-matched to the cases by age and sex. Information on OSA symptoms (excessive daytime sleepiness and sleep related apnea symptoms), gastroesophageal reflux symptoms and anthropometric measures were collected through interviews and written questionnaires. Multivariable logistic regression provided odds ratios (OR) and 95% confidence intervals (CI), adjusted for potential confounding by BMI and gastroesophageal reflux.

Results

The prevalence of Barrett’s esophagus was higher among people with excessive daytime sleepiness than those without (24% vs. 18%; p-value 0.1142) and in participants with sleep-related apnea symptoms (20% vs. 13%; p-value 0.1730). However, there were non-significantly increased ORs of Barrett’s esophagus among people with excessive daytime sleepiness (OR 1.42, 95% CI 0.90–2.34) and sleep related apnea symptoms (OR 1.32, 95% CI 0.74–2.36) when adjusting for age, sex and BMI. After further adjustment for gastroesophageal reflux symptoms, the point ORs were no longer increased (OR 1.02, 95% CI 0.61–1.70 for daytime sleepiness and OR 0.72, 95% CI 0.38–1.38 for sleep related apnea symptoms).

Conclusions

Symptoms of OSA are possibly associated with an increased risk of Barrett’s esophagus, an association that appears to be mediated entirely by gastroesophageal reflux.     

Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

Objective

Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction.

Methods

We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine.

Results

Under 10 cmH₂O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH₂O in the nasal obstruction group but only 1.17 ± 0.29 cmH₂O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups.

Conclusion

This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow velocity was found.     

Obstructive Sleep Apnea Syndrome (OSAS), Metabolic Syndrome and Mental Health in Small Enterprise Workers. Feasibility of an Action for Health

Objective

To determine the frequency of obstructive sleep apnea syndrome (OSAS), metabolic syndrome and common mental disorders in the working population of 11 small enterprises and the feasibility of a program of action for health.

Method

The clinical risk of OSAS, the prevalence of metabolic syndrome, and the level of psychological disorders were assessed during routine medical examination at the workplace in 2012. The response to medical advice was assessed in 2013.

Results

12.3% of the workers were suspected of being affected by OSAS. One or more components of metabolic syndrome were present in 24.5% of cases. OSAS in “healthy” workers was significantly associated with the presence of one or more components of metabolic syndrome (OR = 3.83; 95%CI 1.45–10.13) and with a psychological disorders score in the highest quartile (OR = 4.67; 95%CI = 1.72–12.64). Workers with suspected OSAS were reluctant to follow advice about undergoing further tests under the NHS. However, in some cases, confirmation of the OSAS diagnosis and subsequent treatment led to an improvement in metabolic condition.

Conclusion

Although participation in treatment was limited, anecdotal cases support the idea that prevention of obstructive sleep apnea in the workplace might be useful for workers’ health.     

Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis

Background and Purpose

Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke. Although continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA, whether treating OSA with CPAP reduces the risk of stroke remains unclear. We aimed to evaluate the effects of CPAP on incidence of stroke in patients with OSA.

Materials and Methods

We conducted a systematic review and meta-analysis of all published studies that provided the number of incident strokes in OSA patients in light of their treatment status with CPAP.

Results

We identified 8 relevant studies: one randomized controlled study (RCT), 5 cohort studies, and 2 studies using administrative health data. The two overlapping cohort studies in women and the elderly and the 2 studies using administrative health data had analyzed the impact of CPAP on stroke apart from cardiac events, whereas the others had focused on the overall cardiovascular events. Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14–0.53], and 0.54 [0.38–0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data.

Conclusions

Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence. Such effect was more pronounced in stroke than in cardiac events. Future studies analyzing stroke apart from cardiac disease would be of interest.     

Sleep Related Breathing Disorders and Inflammation — The Missing Link? A Cohort Study Evaluating the Interaction of Inflammation and Sleep Related Breathing Disorders and Effects of Treatment

Introduction

Sleep related breathing disorders (SRBD) are associated with both obesity and systemic inflammation. While the relationship between obesity and SRBD is established, the causality between inflammation and SRBD remains unclear. In this study we investigated the relation between SRBD and C-reactive protein (CRP) as a parameter of inflammation and the influence of SRBD treatment on CRP with additional regard to changes in metabolic and cardiovascular parameters.

Methods

Polysomnography (PSG) and laboratory data of patients diagnosed with SRBD over a period of 5 years were prospectively collected in a database and retrospectively analysed regarding the association of SRBD (according to apnoea-hypopnoea- index (AHI), duration of events and extent of desaturation) to CRP, blood pressure, cholesterol, fasting plasma glucose, HbA1c, quality of life measured via a visual analogue scale (VAS 0–100%), and the effects of SRBD therapy on these parameters.

Results

716 patients were included in the study, 171 with mild SRBD (AHI ≥5 to <15/h), 209 with moderate SRBD (AHI 15 to <30/h), 336 with severe SRBD (AHI ≥30/h). Results according to severity of SRBD. Severe SRBD was significantly associated with elevated levels of CRP (3.7 [1.8–7.0] mg/l, vs. moderate (p = 0.001), and mild SRBD (p<0.001), and higher prevalence of hypertension as compared to moderate and mild SRBD (p<0.001, respectively). Results in highly successful treatment. If SRBD treatment was highly successful (AHI <5/h), CRP and quality of life improved significantly (p = 0.001 and p = 0.002), as did blood pressure (p<0.001 for systolic and diastolic values), although BMI increased (p<0.001). Results in partially successful treatment. If success was defined as reduction of AHI of ≥50%, CRP also decreased (p<0.001), as did blood pressure (p<0.001). Again, BMI increased (p<0.001).

Conclusion

This is the first study to show an association of SRBD and CRP independently of BMI in a large cohort. The SRBD therapy-induced CRP decrease was not associated with BMI changes or metabolic changes but rather with the magnitude of AHI improvement.     

The Potential Association between Obstructive Sleep Apnea and Diabetic Retinopathy in Severe Obesity—The Role of Hypoxemia

Background

Obstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications.

Methods

To investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m²) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA−).

Results

Forty-six patients were OSA+: median (95% CI) AHI = 37(23–74)/hour and 47 were OSA–ve (AHI = 7(4–11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA_1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA− groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65–0.95; p<0.05), after adjustment.

Conclusions

The presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of hypoxemia in patients with OSA and diabetic retinal disease are warranted.     

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity

Rationale

Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention.

Objectives

To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences.

Methods

Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography.

Results

Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m² or visceral fat area ≥100 cm²), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R² = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent.

Conclusions

Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation.     

Cephalometric Pattern and Nasal Patency in Children with Primary Snoring: The Evidence of a Direct Correlation

Introduction

Sleep disordered breathing (SDB) might affect craniofacial growth and children with obstructive sleep apnea syndrome present an increase in total and lower anterior heights of the face and a more anterior and inferior position of the hyoid bone when compared to nasal breathers.

Objective

To investigate the correlation between rhinomanometric and cephalometric parameters in children with primary snoring (PS), without apnea or gas exchange abnormalities.

Materials and Methods

Thirty children with habitual snoring (16 females and 14 males) aged 4–8 years (mean age 6.85±1.51 years) were selected by a SDB validate questionnaire. All subjects underwent lateral cephalometric, panoramic radiographies.

Results

In our sample 10 children (33%) had snoring 3 nights/week, 11 (37%) 4–6 nights/week and 9 (30%) every night/week. Overall 7 patients (23.3%) were affected by adenoid hypertrophy (AH), 4 (13.3%) by tonsillar hypertrophy (TH) and 13 (43.3%) by AH and TH. We found a more vertical position of the hyoid bone to the mandibular plane (H⊥VT) in patients with a higher frequency (7.3±2.7 vs 7.6±3.7 vs 10.9±2.5 in children snoring 3 nights/week, 4–6 nights/week and every night/week respectively; p = 0.032). Concerning nasal patency significant correlations were found with ANB (maxillary and jaw position with respect to the cranial base), NS∧Ar (growth predictor), sumangle, FMA (total divergence), SnaSnp∧GoMe (inferior divergence), BaN∧PtGn (facial growth pattern), Phw1_PsP (posterosuperior airway space), AHC3H (the horizontal distance between the most anterosuperior point of the hyoid bone and the third cervical vertebra).

Conclusion

The present study supports the relationship between nasal obstruction and specific craniofacial characteristics in children with primary snoring and lead us to hypothesize that nasal obstruction might explain the indirect link between snoring and cephalometric alterations.     

Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

Background

Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.

Methods and Results

82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P = 0.0002, BMI: P = 0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P = 0.03, stroke volume: P = 0.042), and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 5–14, 66.4±8.8%, 68.5±10.6% [P = ns]; AHI 15–30∶59.8±7.7%, 68.6±9.3% [P = 0.002]; AHI>30∶54.1±12.4%, 68.2±13.6%[P<0.0001]; apical RV-Sl: AHI 5–14: −17.3±8.7%, −16.0±10.8% [P = ns], AHI 15–30: −9.8±6.0%, −15.4±10.9% [P = 0.028], AHI>30: −6.3±5.7%, −17.9±11.2% [P<0.0001]).

Conclusions

OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.