Waking up to sleep-disordered breathing.

In 1997 Wright and colleagues published a systematic review on the health effects of obstructive sleep apnoea syndrome (OSA) and the effectiveness of treatment with continuous positive airway pressure (CPAP). They concluded that there was limited evidence of increased mortality or morbidity in patients with OSA, and that the evidence linking the condition to cardiovascular risk factors and motor vehicle crashes was conflicting and inconclusive. They also concluded that, although CPAP had been shown to improve daytime sleepiness, there were insufficient data to determine its effect on quality of life, morbidity or mortality. This review generated much controversy, but was a wake-up call to investigators in this field that all were not convinced that OSA was an important condition that always warranted treatment. At that time, our understanding of OSA and the impact of CPAP treatment was at a similar stage to where we were with cardiovascular risk factors such as systemic hypertension, diabetes and hypercholesterolaemia several decades ago. Considerable progress has been made since this review, and many of the issues which it raised have subsequently been addressed in papers published in Thorax. Systemic hypertension has been reported in epidemiological and hospitalbased studies of patients with OSA, and is independent of obesity and the other common risk factors for hypertension which are also frequently present in this patient population. There have been conflicting data as to whether nasal CPAP can effectively reduce blood pressure in patients with OSA. Hui and associates performed a randomised controlled study in 56 patients with moderate to severe OSA and daytime sleepiness which showed that 12 weeks of therapeutic CPAP reduced 24 h mean and diastolic blood pressure by 3.8 mmHg and 3.5 mmHg, respectively. No predictors of the change in blood pressure with CPAP treatment have been convincingly identified. Robinson and coworkers performed a prospective study to determine predictors of blood pressure change. 24 h blood pressure monitoring was performed on 86 patients with OSA and daytime sleepiness prior to and 6 months after CPAP treatment. The mean 24 h blood pressure decreased from 101.0 mmHg to 96.1 mmHg. The decrease in Epworth sleepiness score and the body mass index were the only significant independent predictors of the decrease in 24 h blood pressure. Baseline severity of OSA and overnight hypoxaemia were not independent predictors of the decrease in blood pressure. These results suggest that sleep fragmentation and its effects may be more important than hypoxaemia in the pathogenesis of the hypertension associated with OSA. Type 2 diabetes is a condition of impaired glucose tolerance and insulin resistance which also has a strong causal relationship with central obesity. West and associates surveyed 1682 men with type 2 diabetes from hospital and primary care practitioner databases. Selected respondents had overnight oximetry to establish whether they had OSA. OSA was highly prevalent in men with type 2 diabetes, most of whom were undiagnosed at the time of the study. Recognition and treatment of OSA in this patient population would be beneficial, especially if they have daytime sleepiness. Excessive daytime sleepiness, obesity and insulin resistance occur frequently in patients with OSA. Ronksley and colleagues performed a cross-sectional analysis of diabetes and subjective sleepiness in 2149 patients referred for suspected OSA. The prevalence of diabetes increased with greater OSA severity. After correcting for confounding factors, severe OSA was only associated with diabetes in patients with excessive daytime sleepiness. Excessive daytime sleepiness may be a useful clinical marker to identify patients with OSA at risk of metabolic syndrome. Barcelo and coworkers examined insulin resistance in 44 patients with OSA with and without excessive daytime sleepiness matched for age, body mass index and severity of OSA and 23 healthy controls. Patients with OSA were re-examined after 3 months of CPAP treatment. Patients with excessive daytime sleepiness had higher plasma levels of glucose and insulin as well as evidence of insulin resistance compared with patients without excessive daytime sleepiness or healthy controls. CPAP treatment reduced insulin resistance in patients with excessive daytime sleepiness but not in those without excessive daytime sleepiness. These findings are analogous to the blood pressure studies described above whereby the decrease in subjective sleepiness predicted the decline in 24 h blood pressure with CPAP treatment. West and colleagues reported a double-blind randomised placebo controlled trial of CPAP treatment in 42 patients with OSA and diabetes over 3 months. Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups. Cross and associates performed a randomised double-blind placebo controlled crossover trial to compare vascular function and examine the impact ofCPAP treatment in 46 patients with OSAwith and without sleep hypoxaemia. Patients with OSA and sleep hypoxaemia had impaired endothelial vasodilation that was proportional to their hypoxaemia and improved with CPAP therapy. Kohler and colleagues reported no change in cardiovascular inflammatory markers in a randomised controlled trial of 100 men with moderate to severe OSA treated with CPAP for 4 weeks. These outcomes represent surrogate markers, and the changes in themcannot be extrapolated to infer a reduction in cardiovascular events. The effectiveness of drug treatments such as thrombolysis, aspirin and lipid-lowering treatment in reducing cardiovascular events has been assessed in large long-term randomised controlled trials. Preliminary results of such a trial of CPAP treatment in patientswithOSAhave recently been presented. Barbé and colleagues performed a randomised controlled trial of CPAP versus conservative treatment over 4 years in 724 non-sleepy patients with OSA to evaluate the effect of CPAP treatment on a compositemeasure of incident cardiovascular events and hypertension. There were 58 cardiovascular events and 148 new cases of hypertension. CPAP treatment significantly reduced the incidence of cardiovascular events and hypertension in those patients who used CPAP for at least 4 h/night. The hallmark symptom of OSA is daytime sleepiness, and there is increasing evidence that OSA is associated with an Correspondence to J A Fleetham, The Lung Centre, Respiratory Division, Vancouver Hospital, 7th Floor, 2775 Laurel Street, Vancouver, BC, Canada V5Z 1M9; [email protected]