To ascertain whether objectively measured obstructive sleep apnea (OSA) independently increases the risk of all cause death, cardiovascular disease (CVD), coronary heart disease (CHD), stroke or cancer. Community-based cohort. 400 residents of the Western Australian town of Busselton. OSA severity was quantified via the respiratory disturbance index (RDI) as measured by a single night recording in November-December 1990 using the MESAM IV device, along with a range of other risk factors. Follow-up for deaths and hospitalizations was ascertained via record linkage to the end of 2010. We had follow-up data in 397 people and then removed those with a previous stroke (n = 4) from the mortality/ CVD/CHD/stroke analyses and those with cancer history from the cancer analyses (n = 7). There were 77 deaths, 103 cardiovascular events (31 strokes, 59 CHD) and 125 incident cases of cancer (39 cancer fatalities) during 20 years follow-up. In fully adjusted models, moderate-severe OSA was significantly associated with all-cause mortality (HR = 4.2; 95% CI 1.9, 9.2), cancer mortality (3.4; 1.1, 10.2), incident cancer (2.5; 1.2, 5.0), and stroke (3.7; 1.2, 11.8), but not significantly with CVD (1.9; 0.75, 4.6) or CHD incidence (1.1; 0.24, 4.6). Mild sleep apnea was associated with a halving in mortality (0.5; 0.27, 0.99), but no other outcome, after control for leading risk factors. Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality, incident stroke, and cancer incidence and mortality in this community-based sample.

Background:. Previously published cohort studies in clinical populations have suggested that obstructive sleep apnea (OSA) is a risk factor for mortali

Mirtazapine is an α_2A antagonist and mixed 5-HT₂/5-HT₃ antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials. Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10–40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA. Two patients withdrew from Study 1 after complaints of unacceptable lethargy. Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects. No measurement of sleep apnea improved due to mirtazapine in either study. Weight gain was significantly greater on mirtazapine than on placebo in both trials. Mirtazapine did not improve sleep apnea in either trial. Mirtazapine caused weight gain, which may further worsen OSA. Therefore, mirtazapine is not recommended for the treatment of OSA.

Background: Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2–4% of the middle aged population. Meta-analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5–30/hour). Methods: A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5–30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness. Results: Meta-analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit −0.2 minutes, 95% CI −1.0 to 0.6, p = 0.6). The two significant effects were small (effect size <0.30). Conclusions: CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.