Elsevier

The Lancet

Volume 365, Issue 9464, 19–25 March 2005, Pages 1046-1053
The Lancet

Articles
Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study

https://doi.org/10.1016/S0140-6736(05)71141-7Get rights and content

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.

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, 4, 5, 6, 7, 8, 9, 10 However, the epidemiological studies that provided evidence for this association3, 4, 5 had important methodological limitations. These studies were either retrospective3, 4 or did not take into account the role of potential confounding factors, such as the presence of comorbidity.3, 4, 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, 15, 16, 17, 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.

Section snippets

Patients

We recruited men with obstructive sleep apnoea-hypopnoea or simple snorers from those referred to our sleep unit between Jan 1, 1992, and Dec 31, 1994. During this inclusion period, in keeping with the guidelines of the Spanish Society of Pneumology and Thoracic Surgery,19 nasal CPAP was recommended to all patients who had more than 30 episodes of apnoea or hypopnoea per hour of sleep (ie, apnoea-hypopnoea index [AHI] >30).19 CPAP was also recommended if the AHI was between 5 and 30 and the

Results

We enrolled 277 age-matched and BMI-matched healthy men, 389 men with simple snoring, 409 patients with mild-moderate obstructive sleep apnoea-hypopnoea, and 667 patients with severe disease (or mild-moderate disease plus severe daytime sleepiness [n=38]). CPAP was declined by 241 patients, and 52 patients (43 with AHI >30, and nine with AHI 5–30) were judged non-compliant with CPAP treatment and were excluded from the final analysis (figure 1). However, mean age, BMI, and AHI for this subgroup

Discussion

We have shown that incidence of fatal and non-fatal cardiovascular events in untreated patients with severe obstructive sleep apnoea-hypopnoea is significantly higher than in healthy participants recruited from the general population matched individually for age and BMI. Furthermore, there seems to be a dose-effect relation for this association. Treatment with CPAP significantly reduces cardiovascular risk in patients with severe obstructive sleep apnoea-hypopnoea. Simple snoring does not

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