We studied vasoconstrictor sensitivity and cholinergic responsiveness of the forearm vasculature in 10 male patients with obstructive sleep apnea (OSA) and 10 healthy controls. Subjects with regular medication, known arterial hypertension, diabetes mellitus, or dyslipidemia were not included in this study. Age, body mass index, blood pressure, blood glucose, serum lipids, and baseline forearm vascular conductance (derived from venous occlusion plethysmography and intra-arterial blood pressure measurement) did not differ significantly between these two groups. With use of three dosage steps each, angiotensin II and acetylcholine were successively infused into the brachial artery. During infusion of angiotensin II, mean conductance was 39.6% lower (P = 0.002) in the OSA patients compared with that in the control subjects. Vascular responsiveness to increasing dosages of acetylcholine was not significantly altered in the OSA group. These findings suggest an enhanced vasoconstrictor sensitivity in the forearm vasculature in OSA. The hypothesis that endothelial function in OSA is impaired independently of other cardiovascular risk factors is not supported by the present results.

Objective: To address the influence of gender and obstructive sleep apnea (OSA) on development of diabetes mellitus (DM) in a sleep clinic cohort. Design: A longitudinal observational study. Participants: A consecutive middle-aged (30-69 years) sleep clinic cohort from 1991 (n = 318; 254 men, 64 women) with eligible baseline characteristics, clinical charts, and information from the Swedish Hospital Discharge Registry were identified. Ten individuals with DM at baseline and 47 patients who died during the follow-up period were excluded. Measurements: The remaining 261 subjects were asked to complete a postal questionnaire regarding concomitant diseases including DM, diagnosed by a physician. Results: In total, 168 patients (64.4%) replied. The incidence of DM was 24.9% in patients with OSA (overnight oxygen de-saturations ≥ 30 in 1991) compared with 10.8% in subjects without OSA (p = 0.020). New-onset DM in men was 19.1% in OSA vs 11.1% in non-OSA (n.s.), while the corresponding values in women were 50.0% in OSA and 9.5% in non-OSA (p = 0.022). In a multivariate analysis, DM was predicted by OSA in women with an odds ratio (OR) of 11.8, but not by age, body mass index (BMI) at baseline, or weight change at followup. In men, only BMI (OR 1.16) predicted DM. Conclusion:The contribution of OSA to DM development seems to be gender-dependent and higher in women than in men.

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.

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