Thomas Gaisl

CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis

IMPORTANCE Obstructive sleep apnea is associated with higher levels of blood pressure (BP), which can lead to increased cardiovascular risk. OBJECTIVE To compare the association of continuous positive airway pressure (CPAP), mandibular advancement devices (MADs), and inactive control groups (placebo or no treatment) with changes in systolic BP (SBP) and diastolic BP (DBP) in patients with obstructive sleep apnea. DATA SOURCES The databases of MEDLINE, EMBASE, and the Cochrane Library were searched up to the end of August 2015 and study bibliographies were reviewed. STUDY SELECTION Randomized clinical trials comparing the effect of CPAP or MADs (vs each other or an inactive control) on BP in patients with obstructive sleep apnea were selected by consensus. Of 872 studies initially identified, 51 were selected for analysis. DATA EXTRACTION AND SYNTHESIS Data were extracted by one reviewer and checked by another reviewer. A network meta-analysis using multivariate random-effects meta-regression was used to estimate pooled differences between each intervention. Meta-regression was used to assess the association between trial characteristics and the reported effects of CPAP vs inactive control. MAIN OUTCOMES AND MEASURES Absolute change in SBP and DBP from baseline to follow-up. RESULTS Of the 51 studies included in the analysis (4888 patients), 44 compared CPAP with an inactive control, 3 compared MADs with an inactive control, 1 compared CPAP with an MAD, and 3 compared CPAP, MADs, and an inactive control. Compared with an inactive control, CPAP was associated with a reduction in SBP of 2.5 mm Hg (95% CI, 1.5 to 3.5 mm Hg; P < .001) and in DBP of 2.0 mm Hg (95% CI, 1.3 to 2.7 mm Hg; P < .001). A 1-hour-per-night increase in mean CPAP use was associated with an additional reduction in SBP of 1.5 mm Hg (95% CI, 0.8 to 2.3 mm Hg; P < .001) and an additional reduction in DBP of 0.9 mm Hg (95% CI, 0.3 to 1.4 mm Hg; P = .001). Compared with an inactive control, MADs were associated with a reduction in SBP of 2.1 mm Hg (95% CI, 0.8 to 3.4 mm Hg; P = .002) and in DBP of 1.9 mm Hg (95% CI, 0.5 to 3.2 mm Hg; P = .008). There was no significant difference between CPAP and MADs in their association with change in SBP (-0.5 mm Hg [95% CI, -2.0 to 1.0 mm Hg]; P = .55) or in DBP (-0.2 mm Hg [95% CI, -1.6 to 1.3 mm Hg]; P = .82). CONCLUSIONS AND RELEVANCE Among patients with obstructive sleep apnea, both CPAP and MADs were associated with reductions in BP. Network meta-analysis did not identify a statistically significant difference between the BP outcomes associated with these therapies.

Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis

BACKGROUND Excessive daytime sleepiness is the most important symptom of obstructive sleep apnoea and can affect work productivity, quality of life, and the risk of road traffic accidents. We aimed to quantify the effects of the two main treatments for obstructive sleep apnoea (continuous positive airway pressure and mandibular advancement devices) on daytime sleepiness and to establish predictors of response to continuous positive airway pressure. METHODS We searched MEDLINE and the Cochrane Library from inception to May 31, 2015, to identify randomised controlled trials comparing the effects of continuous positive airway pressure, mandibular advancement devices or an inactive control (eg, placebo or no treatment) on the Epworth Sleepiness Scale (ESS, range 0-24 points) in patients with obstructive sleep apnoea. We did a network meta-analysis using multivariate random-effects meta-regression to assess the effect of each treatment on ESS. We used meta-regression to assess the association of the reported effects of continuous positive airway pressure versus inactive controls with the characteristics of trials and their risk of bias. FINDINGS We included 67 studies comprising 6873 patients in the meta-analysis. Compared with an inactive control, continuous positive airway pressure was associated with a reduction in ESS score of 2·5 points (95% CI 2·0-2·9) and mandibular advancement devices of 1·7 points (1·1-2·3). We estimated that, on average, continuous positive airway pressure reduced the ESS score by a further 0·8 points compared with mandibular advancement devices (95% CI 0·1-1·4; p=0·015). However, there was a possibility of publication bias in favour of continuous positive airway pressure that might have resulted in this difference. We noted no evidence that studies reporting higher continuous positive airway pressure adherence also reported larger treatment effects (p=0·70). INTERPRETATION Continuous positive airway pressure and mandibular advancement devices are effective treatments for reducing daytime sleepiness in patients with obstructive sleep apnoea. Continuous positive airway pressure seemed to be a more effective treatment than mandibular advancement devices, and had an increasingly larger effect in more severe or sleepier obstructive sleep apnoea patients when compared with inactive controls. However, mandibular advancement devices are an effective alternative treatment should continuous positive airway pressure not be tolerated. FUNDING Swiss National Science Foundation and the University of Zurich Clinical Research Priority Program Sleep and Health.

Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patients phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism which can be analysed by mass spectrometry within minutes. The objective of this study was to identify a breath profile in OSA recurrence by use of secondary-electrospray-ionization-mass spectrometry (SESI-MS). Methods Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Exhaled breath analysis by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. The primary outcome was the change in exhaled molecular breath pattern. Results 30 patients with OSA were randomised and 26 completed the trial according to the protocol. CPAP withdrawal led to a recurrence of OSA (mean difference in change of oxygen desaturation index between groups +30.3/h; 95% CI 19.8/h,40.7/h, p<0.001) which was accompanied by a significant change in 62 exhaled features (16 metabolites identified). The panel of discriminating mass-spectral features allowed differentiation between treated and untreated OSA with a sensitivity of 92.9% and a specificity of 84.6%. Conclusion Exhaled breath analysis by SESI-MS allows rapid and accurate detection of OSA recurrence. The technique has the potential to characterise an individuals metabolic response to OSA and thus makes a comprehensible phenotyping of OSA possible. Trial registration number NCT02050425 (registered at ClinicalTrials.gov).

The impact of obstructive sleep apnoea on the aorta

Obstructive sleep apnoea (OSA) has been shown to be a causal factor in the pathogenesis of vascular dysfunction and hypertension, conditions which can promote dilation and subsequent aortic dissection and rupture. The objective of this review is to summarise the current literature on the possible association between OSA and aortic disease and delineate the underlying mechanisms. Relevant studies were found by searching for terms including “obstructive sleep apnoea” in combination with “aortic aneurysm, dissection, and dilation” in the MEDLINE and EMBASE databases. Observational studies consistently reported that OSA is highly prevalent among patients with aortic aneurysms and aortic dissections. Patients with co-occurring OSA and Marfans syndrome as well as patients at the more severe end of the spectrum of OSA seem to be especially vulnerable to aortic disease. Several mechanisms are discussed concerning the link between OSA and aortic disease: nocturnal negative intrathoracic pressure surges leading to mechanical stretching of the aorta and ultimately aortic distension; arousal-induced reflex sympathetic activation with subsequent hypertension; and intermittent hypoxia associated with autonomic nervous system activation and consequently increased oxidative stress. Further well controlled studies are needed in order to define the exact role of OSA as a risk factor for aortic disease. Several studies have shown an association between obstructive sleep apnoea and aortic aneurysms/dissections http://ow.ly/Nh9jc

Detection and Quantification of Benzothiazoles in Exhaled Breath and Exhaled Breath Condensate by Real-Time Secondary Electrospray Ionization-High-Resolution Mass Spectrometry and Ultra-High Performance Liquid Chromatography

2-Subtituted benzothiazoles are widely used industrial chemicals whose occurrence in environmental samples has been shown to be ubiquitous. However, knowledge about human exposure to these compounds and their excretion route is still scarce. Here, we demonstrate for the first time the detection of benzothiazole derivatives in exhaled breath. Real-time analysis of breath was carried out by means of secondary electrospray ionization coupled to high-resolution mass spectrometry. This coupling allowed not only the detection of these compounds in breath with a sensitivity in the pptv range but also their robust identification by comparing tandem high-resolution mass spectra from breath and standards. For further confirmation, benzothiazoles were also determined in exhaled breath condensate samples by means of ultra high-performance liquid chromatography. This approach strengthened the identification as a result of excellent matches in retention times and also allowed quantification. An estimated total daily exhalation of ca. 20 μg day(-1) was calculated for the six benzothiazole derivatives found in breath.

Coronary artery calcification, epicardial fat burden, and cardiovascular events in chronic obstructive pulmonary disease.

Rationale Patients with chronic obstructive pulmonary disease (COPD) suffer from significantly more cardiovascular comorbidity and mortality than would be anticipated from conventional risk factors. The aim of this study was to determine whether COPD patients have a higher coronary artery calcium score (CACS) and epicardial fat burden, compared to control subjects, and their association with cardiovascular events. Methods From a registry of 1906 patients 81 patients with clinically diagnosed COPD were one-to-one matched to 81 non-COPD control subjects with a smoking history, according to their age, sex, and the number of classic cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, family history of premature coronary artery disease). CACS, epicardial fat, and subsequent major adverse cardiovascular events (MACE) during follow-up were compared between groups. Results Patients with COPD (Global Initiative for Chronic Obstructive Lung Disease-classification I: 5%, II: 23%, III: 16% and IV: 56%) showed no difference in CACS (median difference 68 Agatston Units [95% confidence interval -176.5 to 192.5], p=0.899) or epicardial fat volume (mean difference -0.5 cm3 [95% confidence interval -20.9 to 21.9], p=0.961) compared with controls. After a median follow-up of 42.6 months a higher incidence of MACE was observed in COPD patients (RR=2.80, p=0.016) compared with controls. Cox proportional hazard regression identified cardiac ischemias and CACS as independent predictors for MACE. Conclusion COPD patients experienced a higher MACE incidence compared to controls despite no baseline differences in coronary calcification and epicardial fat burden. Other mechanisms such as undersupply of medication seem to account for an excess cardiovascular comorbidity in COPD patients.

Intrathoracic pressure swings induced by simulated obstructive sleep apnoea promote arrhythmias in paroxysmal atrial fibrillation

AIMS There is preliminary evidence for a link between obstructive sleep apnoea (OSA) and arrhythmias such as paroxysmal atrial fibrillation (PAF) and sudden cardiac death but underlying mechanisms remain largely unknown. METHODS AND RESULTS In this interventional crossover study, we evaluated whether intrathoracic pressure changes, induced by simulated OSA, trigger premature cardiac beats, and alter measures of ventricular repolarization [QTc and Tpeak-to-Tend (TpTec) intervals] in patients with PAF. 12-Lead-electrocardiograms were recorded continuously in 44 patients, while simulating obstructive apnoea (Mueller manoeuvre, MM), obstructive hypopnoea (inspiration through a threshold load, ITH), end-expiratory central apnoea (AP), and during normal breathing (NB) in randomized order. The prevalence of OSA in these 44 patients was assessed by a sleep study. Atrial premature beats (APBs) occurred more frequently during MM (55% of patients) and ITH (32%), but not during AP (14%), compared with NB (9%) (P < 0.001, P = 0.006 and P = 0.688, respectively). Mueller manoeuvre led to a significant prolongation of QTc and TpTec intervals (+17.3 ms, P < 0.001 and +4.3 ms, P = 0.005). Inspiration through a threshold load significantly increased QTc (+9.6 ms, P < 0.001) but not TpTec. End-expiratory central apnoea did not alter QTc and TpTec intervals. According to the sleep study, 56% of patients had OSA (apnoea hypopnoea index ≥5). CONCLUSION Simulated OSA induces APBs which may be important in patients with PAF, because the majority of episodes of PAF has been shown to be triggered by APBs. Simulated OSA leads to a significant prolongation of ventricular repolarization.

Simulated Obstructive Sleep Apnea Increases P-Wave Duration and P-Wave Dispersion.

Background A high P-wave duration and dispersion (Pd) have been reported to be a prognostic factor for the occurrence of paroxysmal atrial fibrillation (PAF), a condition linked to obstructive sleep apnea (OSA). We tested the hypothesis of whether a short-term increase of P-wave duration and Pd can be induced by respiratory manoeuvres simulating OSA in healthy subjects and in patients with PAF. Methods 12-lead-electrocardiography (ECG) was recorded continuously in 24 healthy subjects and 33 patients with PAF, while simulating obstructive apnea (Mueller manoeuvre, MM), obstructive hypopnea (inspiration through a threshold load, ITH), central apnea (AP), and during normal breathing (BL) in randomized order. The P-wave duration and Pd was calculated by using dedicated software for ECG-analysis. Results P-wave duration and Pd significantly increased during MM and ITH compared to BL in all subjects (+13.1ms and +13.8ms during MM; +11.7ms and +12.9ms during ITH; p<0.001 for all comparisons). In MM, the increase was larger in healthy subjects when compared to patients with PAF (p<0.05). Conclusion Intrathoracic pressure swings through simulated obstructive sleep apnea increase P-wave duration and Pd in healthy subjects and in patients with PAF. Our findings imply that intrathoracic pressure swings prolong the intra-atrial and inter-atrial conduction time and therefore may represent an independent trigger factor for the development for PAF.

Prevalence and Risk Factors of Sleep Disordered Breathing in Fabry disease: A Prospective Cohort Study.

AbstractExcessive daytime sleepiness (EDS) is a frequently reported and not well-understood symptom in patients with Fabry disease (FD). Sleep-disordered breathing (SDB) is a possible factor. As deposition of glycosphingolipids in the upper airway muscles is likely, we hypothesized that obstructive sleep apnoea (OSA) is highly prevalent in FD and positively associated with its severity.All patients with FD who are followed in the Fabry cohort of the University Hospital Zurich (n = 62) were asked to participate in this prospective cohort study. Eligible patients were prospectively investigated by assessing their daytime sleepiness using the Epworth Sleepiness Scale (ESS), the severity of FD using the Mainz Severity Score Index (MSSI), and by an ambulatory overnight respiratory polygraphy between November 1, 2013, and January 31, 2015. SDB was defined as an apnea/hypopnea index (AHI) of > 5/h.Fifty-two patients (mean ± SD age 42.8 ± 14.7 years, 33% men, mean ± SD BMI 23.4 ± 3.6 kg/m2) with a median (IQR) MSSI of 12 (5–19) were included. Median (IQR) ESS was 6 (2–10) and 7 patients (14%) had an ESS > 10. Thirteen patients (25%) had SDB (78% obstructive sleep apnea, 22% central sleep apnea). In the multivariable analysis, the age was the only statistically significant predictor of SDB (OR 1.11, 95% CI 1.04–1.18, P = 0.001). ESS was associated with depression (P < 0.001) but not AHI nor age.This study shows that SDB, especially obstructive sleep apnea is highly prevalent in patients with Fabry disease. However, EDS in FD seems to be related with depression rather than SDB.ClinicalTrials.gov (identifier: NCT01947634).

Quantification of epicardial and intrathoracic fat volume does not provide an added prognostic value as an adjunct to coronary artery calcium score and myocardial perfusion single-photon emission computed tomography

AIMS To compare the predictive value of epicardial and intrathoracic fat volume (EFV, IFV), coronary artery calcium (CAC) score, and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for major adverse cardiac events (MACE). METHODS AND RESULTS Follow-up was obtained in 275 patients with known or suspected coronary artery disease (CAD), who underwent SPECT-MPI including non-contrast cardiac computed tomography (CT) for attenuation correction to evaluate ischaemic heart disease and in whom EFV, IFV, and CAC score were calculated from non-contrast CT. Associations between fat volume, traditional cardiovascular risk factors, CAC score, and SPECT-MPI results were assessed and MACE predictors identified by Cox proportional hazard regression and global χ(2) statistics. After a median follow-up of 2.9 years, MACE were recorded in 38 patients. In univariate Cox regression analysis, EFV and IFV were predictors of MACE (P = 0.013 and P = 0.004, respectively). In multivariate analysis, EFV and IFV provided incremental predictive value beyond traditional cardiovascular risk factors (P < 0.05 and P < 0.01). However, after adjustment for CAC score and SPECT-MPI results, EFV and IFV fell short of statistical significance as independent outcome predictors. CONCLUSION Quantification of EFV and IFV is associated with MACE and may improve risk stratification beyond traditional cardiovascular risk factors. However, once CAC score and/or SPECT-MPI results are known, EFV and IFV do not provide any added clinically relevant prognostic value. Further studies may identify the subpopulation with the largest relative merit of EFV and IFV as an adjunct to SPECT-MPI and CAC score.