The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?

RATIONALE: Placebo responses are complex psychobiological phenomena and often involve patient expectation of benefit. With continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea, greater hours of CPAP use are associated with reduced sleepiness. However, these open-label studies have not controlled for patient expectation of benefit derived from their knowledge of hours of device use. OBJECTIVES: To investigate the relative effectiveness of the use of real or placebo CPAP on daytime sleepiness. METHODS: Patient-level meta-analysis combining data on sleepiness measured by the Epworth Sleepiness Scale from three randomised placebo-controlled crossover trials. Mixed model analysis of variance was used to quantify the effects of real versus placebo device treatment, usage, their interaction and regression to the mean. MEASUREMENTS AND MAIN RESULTS: Duration of real and placebo CPAP use was correlated within patients (r=0.53, p<0.001). High use of real CPAP reduced sleepiness more than high use of placebo (difference 3.0 points; 95% CI 1.7 to 4.3, p<0.001) and more than low use of real CPAP (difference 3.3; 95% CI 1.9 to 4.7, p<0.0001). High use of placebo was superior to low use of placebo (difference 1.5; 95% CI 0.1 to 2.8, p=0.03). Twenty-nine per cent of the effect of high usage of CPAP (4.2 points; 95% CI 3.3 to 5.1) was explained by the expectation of benefit effect associated with high use of placebo (1.2 points ; 95% CI 0.2 to 2.3). CONCLUSIONS: A clinically significant proportion of the effectiveness of high CPAP use in reducing sleepiness is probably caused by patient expectation of benefit.

Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality. Although it was previously assumed that this was due to its relation with obesity, recent data suggest that OSA is independently associated with the cardiovascular risk factors that comprise metabolic syndrome, including hypertension, insulin resistance, impaired glucose tolerance, and dyslipidaemia. However, as previous studies have only considered these variables individually, it has not been possible to determine the overall association of OSA with this syndrome. METHODS AND RESULTS: We recruited 61 male subjects with OSA and 43 controls. Glucose, insulin, lipids, and blood pressure (BP) were measured following an overnight fast. Insulin resistance was estimated using homeostasis model assessment (HOMA). Metabolic syndrome was diagnosed according to National Cholesterol Education Program (NCEP) criteria. Subjects with OSA were more obese, had higher BP and fasting insulin, were more insulin resistant, had lower HDL cholesterol, and an increased incidence of metabolic syndrome (87% vs. 35%, p<0.0001). In order to determine whether these associations were independent of obesity and other known covariates, a regression analysis adjusted for age, BMI, smoking, and alcohol consumption was performed. This demonstrated that OSA was independently associated with increased systolic and diastolic blood pressure, higher fasting insulin and triglyceride concentrations, decreased HDL cholesterol, increased cholesterol:HDL ratio, and a trend towards higher HOMA values. Metabolic syndrome was 9.1 (95% confidence interval 2.6, 31.2: p<0.0001) times more likely to be present in subjects with OSA. CONCLUSIONS: OSA is independently associated with an increase in the cardiovascular risk factors that comprise the metabolic syndrome and its overall prevalence. This may help explain the increased cardiovascular morbidity and mortality associated with this condition.

Plasma adiponectin increases postprandially in obese, but not in lean, subjects.

OBJECTIVE: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. RESEARCH METHODS AND PROCEDURES: We studied 13 lean and 11 obese subjects after a 10-hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. RESULTS: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) microg/mL vs. 8.6 (6.5 to 11.3) microg/mL], but rose 4-fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) microg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) microg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. DISCUSSION: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.