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Trials are under way to determine the still unclear associations between sleep apnoea and cardiovascular outcomes
The prevalence of obstructive sleep apnoea in its severe form is about 2% and 0.5% in middle aged men and women respectively.1 Pharyngeal collapse during sleep causes recurrent frustrated inspiratory efforts, oscillating levels of blood oxygen, and disturbed sleep, which may, or may not, lead to excessive daytime sleepiness.2 The main treatment for moderate to severe obstructive sleep apnoea and excessive daytime sleepiness (obstructive sleep apnoea syndrome) is nasal continuous positive airway pressure applied during sleep. A meta-analysis3 clearly showed that this treatment is highly effective in preventing apnoea in such patients, thus relieving symptoms and improving self assessed quality of life.4
The main debate over treatment is whether obstructive sleep apnoea is also an important independent risk factor for vascular disease (such as myocardial infarction, heart failure, and stroke), both in those with and without current vascular problems. Some of the potential mechanisms suggested include acute and long term effects on blood pressure, endothelial dysfunction, deoxygenation-reoxygenation injury, increased swings in pleural pressure causing cardiac loading, and increased platelet coagulation. Unfortunately, obstructive sleep apnoea coexists with many features of the metabolic syndrome. Indeed, the condition is common in type 2 diabetes, with a prevalence of 20%,5 and such patients tend to share a similar body shape. Obesity of the upper body provokes obstructive sleep apnoea through deposition of fat in the neck,6 compromising pharyngeal patency, and visceral obesity also provokes insulin resistance, as well as being a better predictor of vascular risk than general obesity.7
This means that cross sectional and cohort studies, apparently linking obstructive sleep apnoea and vascular disease, cannot prove causation (especially as simple indices such as waist to hip ratio do not fully control for visceral fat8), and thus can only generate hypotheses. Obstructive sleep apnoea probably acts partly as a marker for the metabolic syndrome in such studies.
Non-randomised interventional trials have suggested survival advantages from continuous positive airway pressure,9 but the control populations were those who showed poor compliance with the treatment. Unfortunately, patients who are poor compliers with trial treatments have a higher mortality anyway, presumably because of poorer compliance with other treatments. Because of the imperative to treat symptomatic patients, most randomised controlled trials of treatment in obstructive sleep apnoea have been short term, looking only at surrogate end points for vascular disease, such as blood pressure, insulin resistance, inflammatory markers, and cardiac function. Hence they have not yielded robust evidence for an independent effect of obstructive sleep apnoea on vascular outcomes.
Several studies have shown a fall of up to 10 mm Hg in mean 24 h blood pressure in patients treated with continuous positive airway pressure compared with controls3; the largest reductions occurred in the most severe and symptomatic patients.10 Furthermore, echocardiography and gated nuclear scanning have shown improvements in left ventricular ejection fraction11 and indices of diastolic function.12 However, treatment with continuous positive airway pressure does not seem to improve insulin resistance or glycaemic control in patients with both obstructive sleep apnoea and type 2 diabetes.13
Such surrogate end points can only hint at potential additional vascular morbidity and mortality. Thus, the recent appearance of the first mortality study in patients with heart failure (with left ventricular ejection fraction of ≤45%) and obstructive sleep apnoea is interesting, even though treatment was non-randomised.14 This paper compared mortality in three groups: 113 patients with heart failure, but little or no obstructive sleep apnoea; 37 such patients with untreated moderate to severe obstructive sleep apnoea; and 14 with obstructive sleep apnoea treated with continuous positive airway pressure.
The presence of untreated obstructive sleep apnoea seemed to double mortality from heart failure over five years from 12% to 24%, and there were no deaths in the small group treated with continuous positive airway pressure. Although this study would have been subject to unrecognised confounders and non-randomisation bias, the size of the effect suggests that people looking after patients with heart failure should be more aware of the detrimental impact of obstructive sleep apnoea.
How can robust long term evidence be collected in this area? Patients with moderate to severe symptoms cannot be entered into placebo controlled trials because they should be offered treatment. Because no robust evidence indicates that patients with asymptomatic obstructive sleep apnoea should be treated to reduce vascular risk, clinicians can ethically randomise such patients to long term trials of continuous positive airway pressure versus no treatment. Such trials are in their infancy, and outcomes for morbidity and mortality will take a long time to gather. But without them we will not know whether to offer this treatment for vascular benefits to patients with asymptomatic obstructive sleep apnoea.
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.