Rationale: Continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) therapy are commonly used to treat obstructive sleep apnea (OSA). Differences in efficacy and compliance of these treatments are likely to influence improvements in health outcomes. Objectives: To compare health effects after 1 month of optimal CPAP and MAD therapy in OSA. Methods: In this randomized crossover trial, we compared the effects of 1 month each of CPAP and MAD treatment on cardiovascular and neurobehavioral outcomes. Measurements and Main Results: Cardiovascular (24-h blood pressure, arterial stiffness), neurobehavioral (subjective sleepiness, driving simulator performance), and quality of life (Functional Outcomes of Sleep Questionnaire, Short Form-36) were compared between treatments. Our primary outcome was 24-hour mean arterial pressure. A total of 126 patients with moderate-severe OSA (apnea hypopnea index [AHI], 25.6 [SD 12.3]) were randomly assigned to a treatment order and 108 completed the trial with both devices. CPAP was more efficacious than MAD in reducing AHI (CPAP AHI, 4.5 ± 6.6/h; MAD AHI, 11.1 ± 12.1/h; P < 0.01) but reported compliance was higher on MAD (MAD, 6.50 ± 1.3 h per night vs. CPAP, 5.20 ± 2 h per night; P < 0.00001). The 24-hour mean arterial pressure was not inferior on treatment with MAD compared with CPAP (CPAP-MAD difference, 0.2 mm Hg [95% confidence interval, −0.7 to 1.1]); however, overall, neither treatment improved blood pressure. In contrast, sleepiness, driving simulator performance, and disease-specific quality of life improved on both treatments by similar amounts, although MAD was superior to CPAP for improving four general quality-of-life domains. Conclusions: Important health outcomes were similar after 1 month of optimal MAD and CPAP treatment in patients with moderate-severe OSA. The results may be explained by greater efficacy of CPAP being offset by inferior compliance relative to MAD, resulting in similar effectiveness. Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415).

Objective: To systematically analyze the studies that have examined the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with resistant hypertension and obstructive sleep apnea (OSA). Methods: Design – meta-analysis of observational studies and randomized controlled trials (RCTs) indexed in PubMed and Ovid (All [email protected]). participants: individuals with resistant hypertension and OSA; interventions – CPAP treatment. Results: A total of six studies met the inclusion criteria for preintervention to postintervention analyses. The pooled estimates of mean changes after CPAP treatment for the ambulatory (24-h) SBP and DBP from six studies were −7.21 mmHg [95% confidence interval (CI): −9.04 to −5.38; P < 0.001; I² 58%) and −4.99 mmHg (95% CI: −6.01 to −3.96; P < 0.001; I² 31%), respectively. The pooled estimate of the ambulatory SBP and DBP from the four RCTs showed a mean net change of −6.74 mmHg [95% CI: −9.98 to −3.49; P < 0.001; I² 61%] and −5.94 mmHg (95% CI: −9.40 to −2.47; P = 0.001; I² 76%), respectively, in favor of the CPAP group. Conclusion: The pooled estimate shows a favorable reduction of BP with CPAP treatment in patients with resistant hypertension and OSA. The effects sizes are larger than those previously reported in patients with OSA without resistant hypertension.

Rationale and objectives Impaired insulin sensitivity (ISx), increased visceral abdominal fat (VAF) and liver fat are all central components of the metabolic syndrome and characteristics of men with obstructive sleep apnoea (OSA). The reversibility of these observed changes with continuous positive airway pressure (CPAP) treatment in men with OSA has not been systematically studied in a randomised sham-controlled fashion. Methods 65 men without diabetes who were CPAP naïve and had moderate to severe OSA (age=49±12 years, apnoea hypopnoea index (AHI)=39.9±17.7 events/h, body mass index=31.3±5.2 kg/m²) were randomised to receive either real (n=34) or sham (n=31) CPAP for 12 weeks. At 12 weeks, all subjects received real CPAP for an additional 12 weeks. Measurements and main results Main outcomes were the change at week 12 from baseline in VAF, ISx and liver fat. Other metabolic outcomes were changes in the disposition index, total fat, and blood leptin and adiponectin concentrations. The AHI was lower on CPAP compared with sham by 33 events/h (95% CI−43.9 to −22.2, p<0.0001) after 12 weeks. There were no between-group differences at 12 weeks in VAF (−13.0 cm³, −42.4 to 16.2, p=0.37), ISx (−0.13 (min⁻¹)(μU/ml))⁻¹, −0.40 to 0.14, p=0.33), liver fat (−0.5 cm³, −3.8 to 2.7, p=0.74) or any other cardiometabolic parameter. At 24 weeks, ISx (3.2×10⁴ (min⁻¹)(μU/ml))⁻¹, 0.9×10⁴ to 6.0×10⁴, p=0.009), but not VAF (−1.4 cm³, −19.2 to 16.4, p=0.87) or liver fat (−0.2 Hounsfield units, −2.4 to 2.0, p=0.83) were improved compared with baseline in the whole study group. Conclusion Reducing visceral adiposity in men with OSA cannot be achieved with CPAP alone and is likely to require weight-loss interventions. Longer-term effects of CPAP on other cardiometabolic markers such as ISx require further investigation to fully examine time dependencies. Trial Registration Number ACTRN12608000301369.

Rationale: Dyslipidemia is common in Obstructive Sleep Apnea (OSA). Postprandial lipidemia (PPL) is a strong marker of cardiovascular risk. Evidence that OSA treatment improves PPL is lacking. Objectives: To investigate the effect of continuous positive airway pressure (CPAP) treatment on postprandial lipidemia (PPL) in patients with obstructive sleep apnea (OSA) in the upper moderate or severe range. Methods: In this randomized, placebo-controlled crossover trial, we compared the effects of 2 months each of therapeutic and placebo CPAP on PPL. Measurements and Main Results: PPL was determined from the area under the 24-hour triglyceride concentration curve (TAG-AUC₂₄) using seven blood samples drawn across both the wake and sleep periods. Secondary outcomes were the difference in other 24-hour lipid profiles. Thirty-eight eligible patients were randomly assigned to a treatment order and 29 patients completed the trial. CPAP reduced PPL compared with placebo with a mean TAG-AUC₂₄ difference of −357 mmol/L/d (95% confidence interval [CI], −687.3 to −26.8; P = 0.035). During both the CPAP and placebo studies, TAG levels peaked during both wakefulness (2:00 p.m.) and sleep (3:00 a.m.). Both peaks were lower during CPAP than placebo: 2:00 p.m., −0.49 mmol/L (95% CI, −0.74 to −0.24; P < 0.0005) and 3:00 a.m., −0.40 mmol/L (95% CI, −0.65 to −0.15; P = 0.002). Moreover, mean 24-hour total cholesterol was −0.19 mmol/L lower on CPAP (95% CI, −0.27 to −0.11; P < 0.00001). Conclusions: This randomized trial demonstrated that treatment of severe OSA with CPAP improves postprandial TAG and total cholesterol levels. These effects may reduce the risk for cardiovascular events. The results imply that the association between OSA and cardiovascular disease may, in part, be caused by direct effects on dyslipidemia. Clinical trial registered with the Australian and New Zealand Clinical Trials Registry at www.anzctr.org.au (ACTRN 12605000066684).

Background: The combination of male gender, obstructive sleep apnoea (OSA) and obesity magnifies cardiometabolic risk. There has been no systematic study evaluating whether testosterone therapy can improve cardiometabolic health in obese men with OSA by improving body composition, visceral abdominal fat and insulin sensitivity.Objective: To assess body compositional and cardiometabolic effects of testosterone treatment in obese men with severe OSA.Design: An 18-week randomised, double-blind, placebo-controlled and parallel group trial in 67 men.Methods: Participants (age=49±12 years, apnoea hypopnoea index=39.9±17.7 events/h, BMI=31.3±5.2 kg/m²) were placed on a hypocaloric diet and received i.m. injections of either 1000 mg testosterone undecanoate (n=33) or placebo (n=34) for 18 weeks. Outcomes were the changes in body composition (total muscle mass, total and abdominal fat, total body dual-energy X-ray absorptiometry and computerised tomography (CT)), weight, insulin sensitivity (homeostasis model assessment), abdominal liver fat (CT), arterial stiffness (pulse wave analysis), resting metabolic rate and respiratory quotient (indirect calorimetry) and blood lipids and metabolic syndrome from baseline to week 18.Results: After 18 weeks, testosterone treatment increased insulin sensitivity (−1.14 units, 95% confidence interval (95% CI) −2.27 to −0.01,P<0.05), reduced liver fat (0.09 Hounsfield attenuation ratio, 95% CI 0.009 to 0.17,P=0.03) and increased muscle mass (1.6 kg, 95% CI 0.69 to 2.5,P=0.0009) to a greater extent than placebo. Other measures of body composition and regional adiposity as well as the number of participants with metabolic syndrome did not change. Testosterone also decreased arterial stiffness (augmentation index) by 3.2% (95% CI −6.01 to −0.46%,P=0.02) and decreased the respiratory quotient (95% CI −0.04, −0.08 to −0.001,P=0.04) after 18 weeks compared with placebo.Conclusion: Eighteen weeks of testosterone therapy in obese men with OSA improved several important cardiometabolic parameters but did not differentially reduce overall weight or the metabolic syndrome. Longer term studies are required.