Articles 1046 www.thelancet.com Vol 365 March 19, 2005 Introduction Obstructive sleep apnoea-hypopnoea affects 4% of middle- aged men and 2% of middle-aged women. 1,2 This disorder is widely accepted to be associated with high rates of morbidity and mortality, mostly due to cardiovascular disease and traffic accidents. 3–10 However, the epidemiological studies that provided evidence for this association 3–5 had important methodological limitations. These studies were either retrospective 3,4 or did not take into account the role of potential confounding factors, such as the presence of comorbidity. 3–5 In fact, after adjustment for age and obesity, studies have not been able to show such increased risk. 6,7,11 Whether there is a link between the severity of obstructive sleep apnoea- hypopnoea and cardiovascular risk; whether simple snoring (ie, snoring without the presence of obstructive sleep apnoea-hypopnoea) increases this risk; and whether effective treatment of the disorder with continuous positive airway pressure (CPAP) can modify or eventually normalise this risk is unclear. These questions have important social and economic implications for public health. 12,13 We did an observational study to address these issues, since a randomised controlled trial, although ideal, would be unethical because the available evidence on the effectiveness of CPAP on symptom control precludes the possibility of withholding treatment for the time needed for the study. 14–18 Since 1992, we have followed up a cohort of patients with obstructive sleep apnoea-hypopnoea and have recorded carefully the incidence of new fatal and non-fatal cardiovascular events. Although all patients with severe obstructive sleep apnoea-hypopnoea were initially offered treatment with CPAP, a substantial proportion refused it; because these individuals were nonetheless followed up in the clinic regularly, they provide information on the natural history of untreated, severe obstructive sleep apnoea-hypopnoea. Methods Patients We recruited men with obstructive sleep apnoea- hypopnoea or simple snorers from those referred to our Lancet 2005; 365: 1046–53 Respiratory Service, Hospital Universitario Miguel Servet, Zaragoza, Spain (J M Marin MD, S J Carrizo MD, E Vicente MD); and Respiratory Service, Hospital Universitario Son Dureta, IUNICS, Palma de Mallorca, Spain (A G N Agusti MD) Correspondence to: Dr Jose M Marin, Servicio de Neurologia, Hospital Universitario Miguel Servet, Isabel la Catolica, 50006 Zaragoza, Spain jmmarint@unizar.es Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study Jose M Marin, Santiago J Carrizo, Eugenio Vicente, Alvar G N Agusti Summary Background The effect of obstructive sleep apnoea-hypopnoea as a cardiovascular risk factor and the potential protective effect of its treatment with continuous positive airway pressure (CPAP) is unclear. We did an observational study to compare incidence of fatal and non-fatal cardiovascular events in simple snorers, patients with untreated obstructive sleep apnoea-hypopnoea, patients treated with CPAP, and healthy men recruited from the general population. Methods We recruited men with obstructive sleep apnoea-hypopnoea or simple snorers from a sleep clinic, and a population-based sample of healthy men, matched for age and body-mass index with the patients with untreated severe obstructive sleep apnoea-hypopnoea. The presence and severity of the disorder was determined with full polysomnography, and the apnoea-hypopnoea index (AHI) was calculated as the average number of apnoeas and hypopnoeas per hour of sleep. Participants were followed-up at least once per year for a mean of 10·1 years (SD 1·6) and CPAP compliance was checked with the built-in meter. Endpoints were fatal cardiovascular events (death from myocardial infarction or stroke) and non-fatal cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, coronary artery bypass surgery, and percutaneous transluminal coronary angiography). Findings 264 healthy men, 377 simple snorers, 403 with untreated mild-moderate obstructive sleep apnoea-hypopnoea, 235 with untreated severe disease, and 372 with the disease and treated with CPAP were included in the analysis. Patients with untreated severe disease had a higher incidence of fatal cardiovascular events (1·06 per 100 person-years) and non-fatal cardiovascular events (2·13 per 100 person-years) than did untreated patients with mild-moderate disease (0·55, p=0·02 and 0·89, p0·0001), simple snorers (0·34, p=0·0006 and 0·58, p0·0001), patients treated with CPAP (0·35, p=0·0008 and 0·64, p0·0001), and healthy participants (0·3, p=0·0012 and 0·45, p0·0001). Multivariate analysis, adjusted for potential confounders, showed that untreated severe obstructive sleep apnoea-hypopnoea significantly increased the risk of fatal (odds ratio 2·87, 95%CI 1·17–7·51) and non-fatal (3·17, 1·12–7·51) cardiovascular events compared with healthy participants. Interpretation In men, severe obstructive sleep apnoea-hypopnoea significantly increases the risk of fatal and non-fatal cardiovascular events. CPAP treatment reduces this risk.