BACKGROUNDObstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. METHODSAfter a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-tosevere obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTSMost of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P = 0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. 920T h e ne w e ngl a nd jou r na l o f m e dicine O bstructive sleep apnea causes episodic hypoxemia and nocturnal sympathetic nervous system activation 1 and elevates blood pressure 2 and markers of oxidative stress, inflammation, and hypercoagulation. 3,4

Rationale: The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized. Objectives: To define carefully the proportion of key anatomic and nonanatomic contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA. Methods: Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway [Pcrit]) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA. Measurements and Main Results: Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 [21.5 Conclusions: This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.

Short and long self-reported sleep durations are independently associated with a modestly increased risk of coronary events.

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Short-term sleep restriction results in impaired glucose tolerance. To test whether habitually short sleep duration increases the risk of developing diabetes, we studied a cohort of 70,026 women enrolled in the Nurses Health Study, without diabetes at baseline, and who responded to a question about daily sleep duration in 1986. Subjects were followed until 1996 for the diagnosis of diabetes (1,969 cases). Long and short sleep durations were associated with an increased risk of diabetes diagnosis. The relative risks (RRs) for short (slept Յ5 h per day) and long (slept Ն9 h per day) sleepers were 1.57 (95% CI 1.28 -1.92) and 1.47 (1.19 -1.80), respectively. After adjustment for BMI and a variety of confounders, the RR was not significantly increased for short sleepers (1.18 [0.96 -1.44]) but remained modestly increased for long sleepers (1.29 [1.05-1.59]). We then performed a similar analysis using only symptomatic cases (n ϭ 1,187). Adjusted RRs for symptomatic diabetes were modestly elevated in both short (1.34 [1.04 -1.72]) and long (1.35 [1.04 -1.75]) sleepers. Our data suggest that the association between a reduced self-reported sleep duration and diabetes diagnosis could be due to confounding by BMI, or sleep restriction may mediate its effects on diabetes through weight gain. Sleep restriction may be an independent risk factor for developing symptomatic diabetes.

These results confirm previous findings that mortality risk in women is lowest among those sleeping 6 to 7 hours. Further research is needed to understand the mechanisms by which short and long sleep times can affect health.

Pharyngeal collapse in obstructive sleep apnea patients is likely a product of a sleep-related decrement in pharyngeal dilator muscle activity superimposed upon abnormal airway anatomy. We postulate that during wakefulness, increased pharyngeal dilator muscle activity in apnea patients compensates for diminished airway size thus maintaining patency. We studied the waking genioglossus (GG) electromyogram (EMG) activity in 11 OSA patients and 14 age-matched controls to determine if GG activity is higher in the awake state in apnea patients than controls. To make this determination, we developed a reproducible methodology whereby true maximal GG EMG could be defined and thus basal activity quantitated as a percentage of this maximal value. Therefore, direct comparisons of basal activity between individuals was possible. We observed apnea patients to have significantly greater basal genioglossal activity compared to controls (40.6±5.6% vs. 12.

Physiologic studies suggest that sleep restriction has metabolic effects that predispose to weight gain. The authors investigated the association between self-reported usual sleep duration and subsequent weight gain in the Nurses' Health Study. The 68,183 women who reported habitual sleep duration in 1986 were followed for 16 years. In analyses adjusted for age and body mass index, women sleeping 5 hours or less gained 1.14 kg (95% confidence interval (CI): 0.49, 1.79) more than did those sleeping 7 hours over 16 years, and women sleeping 6 hours gained 0.71 kg (95% CI: 0.41, 1.00) more. The relative risks of a 15-kg weight gain were 1.32 (95% CI: 1.19, 1.47) and 1.12 (95% CI: 1.06, 1.19) for those sleeping 5 and 6 hours, respectively. The relative risks for incident obesity (body mass index: >30 kg/m(2)) were 1.15 (95% CI: 1.04, 1.26) and 1.06 (95% CI: 1.01, 1.11). These associations remained significant after inclusion of important covariates and were not affected by adjustment for physical activity or dietary consumption. These data suggest that short sleep duration is associated with a modest increase in future weight gain and incident obesity. Further research is needed to understand the mechanisms by which sleep duration may affect weight.