Obstructive sleep apnea (OSA) is common in the general population and highly prevalent in patients with cardiovascular disease. In this paper, we review (1) the pathophysiological mechanisms of OSA that may causally contribute to cardiovascular disease; (2) current evidence regarding the association between OSA and hypertension, stroke, ischemic heart disease, heart failure, atrial fibrillation, and cardiovascular mortality; and (3) the impact of continuous positive airway pressure (CPAP) treatment on cardiovascular risk factors and outcomes. We emphasize the importance of obesity as a comorbidity of OSA and a confounder in the association between OSA and cardiovascular disease. We also discuss the importance of addressing obesity in patients with OSA, as a strategy to reduce the burden of cardiovascular risk factors in this population. Implications for the approach of patients' OSA in clinical practice and future research directions are discussed.

on behalf of the HAROSA I Study Group * BACKGROUND: Excessive daytime sleepiness (EDS) in individuals with OSA syndrome persisting despite good adherence to CPAP is a disabling condition. Pitolisant is a selective histamine H3-receptor antagonist with wake-promoting effects.RESEARCH QUESTION: Is pitolisant effective and safe for reducing daytime sleepiness in individuals with moderate to severe OSA adhering to CPAP treatment but experiencing residual EDS? STUDY DESIGN AND METHODS: In a multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was titrated individually at up to 20 mg/day and taken over 12 weeks. The primary end point was change in the Epworth Sleepiness Scale (ESS) score in the intention-totreat population. Key secondary end points were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, Clinical Global Impressions scale of severity, the patient's global opinion, EuroQoL quality-of-life questionnaire score, Pichot fatigue questionnaire score, and safety.RESULTS: Two hundred forty-four OSA participants (82.8% men; mean age, 53.1 years; mean Apnea Hypopnea Index with CPAP, 4.2/h; baseline ESS score, 14.7) were randomized to pitolisant (n ¼ 183) or placebo (n ¼ 61). ESS significantly decreased with pitolisant compared with placebo (À2.6; 95% CI, -3.9 to À1.4; P < .001), and the rate of responders to therapy (ESS # 10 or change in ESS $ 3) was significantly higher with pitolisant (71.0% vs 54.1%; P ¼ .013). Adverse event occurrence (mainly headache and insomnia) was higher in the pitolisant group compared with the placebo group (47.0% and 32.8%, respectively; P ¼ .03). No cardiovascular or other significant safety concerns were reported.INTERPRETATION: Pitolisant used as adjunct to CPAP therapy for OSA with residual sleepiness despite good CPAP adherence significantly reduced subjective and objective sleepiness and improved participant-reported outcomes and physician-reported disease severity.

Background: The best method for titration of continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) syndrome has not yet been established. The 90th or 95th percentiles of the pressure titrated over time by automatic CPAP (A-CPAP) have been recommended as reference for prescribing therapeutic fixed CPAP (F-CPAP). We compared A-CPAP to F-CPAP, which was determined by a common prediction formula. Methods: Forty-five patients who were habituated to F-CPAP underwent titration polysomnography. In a double-blind, randomized order, each patient used an A-CPAP device in the autotitration and in the fixed pressure mode during one half of the night. Apnea-hypopnea index (AHI) and pressure profiles were primary outcomes. Bias and precision were additionally assessed for both CPAP modes. Results: No significant differences in various sleep parameters or in subjective sleep quality evaluation were found. The AHI was effectively lowered in both CPAP modes (A-CPAP 7.7 [10.8] events/h versus F-CPAP 5.4 [9.0] events/h, p = 0.061). Comparison of group means showed that F-CPAP closely paralleled mean (Pmean) and median (P50), but not the 95th percentile (P95) pressure, of A-CPAP. While bias was lowest for Pmean and P50, there was a lack of precision in all A-CPAP pressure categories. Conclusions: We confirm that F-CPAP set by prediction formula is not worse in terms of AHI control than A-CPAP. On average, F-CPAP parallels Pmean and P50 but not P95. However, due to imprecise matching, individual F-CPAP values cannot be derived from Pmean or P50.

No abstract

No abstract

Background Marfan syndrome (MFS) is an inherited connective tissue disorder characterized by ectopia lentis, aortic root dilation and dissection and specific skeletal features. Obstructive sleep apnea (OSA) in MFS has been described earlier but the prevalence and its relation with the cardiovascular risk is still controversial. This study aimed to further investigate these aspects. Methods In this prospective longitudinal study, we performed an attended polysomnography in 40 MFS patients (60% women, 37 ± 12.8 years) and evaluated several cardiovascular parameters through echocardiography, resting electrocardiogram, 24 hr‐Holter monitoring and serum NT‐ProBNP measurements. Results We found that OSA was present in 42.5% of the patients and that higher body mass index was the most important factor associated with the presence of OSA. We observed that overweight was present in 27.5% of the patients in the whole cohort and in 55.6% if >40 years. Furthermore, when evaluating the impact of OSA on the cardiovascular system, we observed that patients with OSA tended to have higher systolic blood pressure, larger distal aortic diameters and a higher prevalence of ventricular arrhythmia. These differences were, however, not significant after adjusting for confounders. Conclusions Our study shows a high prevalence of OSA and a high prevalence of overweight in MFS patients. We found some trends between OSA and cardiovascular features but we could not establish a solid association. Our study, however might be underpowered, and a multicenter collaborative study could be very useful to answer some important open questions.

No abstract

Background: Gamma-hydroxybutyric acid (GHB), well known as a party drug, especially in Europe, is also legally used (sodium oxybate, Xyrem ® ) to treat a rare sleep disorder, narcolepsy with cataplexy. This exploratory study was set up to measure GHB concentrations in dried blood spots (DBS) collected by narcoleptic patients treated with sodium oxybate. Intra-and inter-individual variation in clinical effects following sodium oxybate administration has been reported. The use of DBS as a sampling technique, which is stated to be easy and convenient, may provide a better insight into GHB concentrations following sodium oxybate intake in a real-life setting. Objective:The aim was two-fold: evaluation of the applicability of a recently developed DBS-based gas chromatography-mass spectrometry (GC-MS) method, and of the feasibility of the sampling technique in an ambulant setting. Methods: Seven narcoleptic patients being treated with sodium oxybate at the Department for RespiratoryDiseases of Ghent University Hospital were asked to collect DBS approximately 20 min after the first sodium oxybate (Xyrem ® ; UCB Pharma Ltd, Brussels, Belgium) intake on a maximum of 7 consecutive days. Using an automatic lancet, patients pricked their fingertip and, after wiping off the first drop of blood, subsequent drops were collected on a DBS card. The DBS cards were sent to the laboratory by regular mail and, before analysis, were visually inspected to record DBS quality (large enough, symmetrically spread on the filter paper with even colouration on both sides of the filter paper). Results:Of the seven patients, three patients succeeded to collect five series of DBS, one patient decided to cease participation because of nausea, one was lost during follow-up and two patients stated falling asleep almost immediately after the intake of sodium oxybate. Analysing the DBS in duplicate resulted in acceptable within-DBS card precision. DBS with acceptable quality were obtained by patients without supervision. Conclusion:Our results demonstrate the acceptable precision of the complete procedure, from sampling at home to quantitative analysis in the laboratory. Given the intra-and inter-individual variability in clinical effects seen with sodium oxybate, the easy adaptation of DBS sampling opens the possibility of following up GHB concentrations in patients in real-life settings in future studies.3