Sleep Disorder Increases Risk of Mortality
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Obstructive sleep apnea increases the risk of death from stroke or other causes, whether the sleeper has hypertension or not, according to research reported today.
Equally disquieting was the news that in patients with both central sleep apnea and heart failure, continuous positive airway pressure (CPAP) improves both sleep and cardiovascular function, but does not improve survival.
Those findings were reported in separate sleep apnea studies published in the Nov. 10 issue of the New England Journal of Medicine.
Obstructive sleep apnea, the more common form, is caused by narrowing or collapse of the airway during sleep due to failure of mechanisms that maintain muscle tone. Central sleep apnea is caused by a neurologic dysfunction originating in the brain stem that causes cessation of breathing during sleep, with episodes lasting up to two minutes, and recurring anywhere from a few to hundreds of times per night.
Sleep apnea has been shown to increase the risk of stroke and transient ischemic attacks, and is associated with coronary heart disease, heart failure, arrhythmias, heart attack, and hypertension.
Whether obstructive sleep apnea is an independent risk factor for stroke or death examined by Vahid Mohsenin, M.D., and colleagues at the Yale Center for Sleep Medicine here.
They conducted an observational cohort study in 1,022 patients. 697 of whom had obstructive sleep apnea, and 325 of whom served as controls.
The patients all underwent polysomnography, and the incidence of strokes and death was recorded. Obstructive sleep apnea was defined as a score on an apnea-hyopnea index of 5 or more, indicating 5 or more episodes per hour. At baseline, the mean index score was 35 among patients with obstructive apnea, compared with two among controls.
Conducting an unadjusted analysis, the authors found that patients with obstructive apnea had a greater than two-fold risk of stroke or death from any cause compared with controls (hazard ratio, 2.24; 95% confidence interval, 1.30 to 3.86; P=0.004).
Even when the data were adjusted for factors such as age, sex, race, smoking status, alcohol-consumption, body-mass index, diabetes mellitus, hyperlipidemia, atrial fibrillation, and hypertension, the obstructive apnea syndrome remained as a statistically significant risk factor for the combined end point of stroke or death (HR, 1.97; 95% CI, 1.12 to 3.48; P=0.01).
“In a trend analysis, increased severity of sleep apnea at baseline was associated with an increased risk of the development of the composite end point (P=0.005),” the investigators wrote.
In the second study, T. Douglas Bradley, M.D., of the department of medicine at the University of Toronto and colleagues at other Canadian centers looked at whether continuous positive airway pressure (CPAP) could help to improve survival in patients with heart failure who also suffer from central sleep apnea.
They randomly assigned a group of 258 heart-failure patients (mean age 63 + 10 years, mean ejection fraction 24.5% + 7.7%) and sleep apnea (40 + 16 episodes per hour) to receive CPAP or no CPAP.
Patients were followed for a mean of two years, until heart transplantation, death, or study end. All patients were assessed at regular intervals for left-ventricular ejection fraction (LVEF), distance walked in six minutes, and quality of life. In addition, at three centers plasma levels of norepinephrine and atrial natriuretic peptide were obtained at three, six, and 24 months.
The investigators found that while the CPAP group appeared to do better on various measures of function, it didn’t make a whit of difference in terms of the major study endpoints.
Specifically, patients who slept with a CPAP device had greater reductions in the frequency of episodes of apnea and hypopnea (-21 ± 16 vs. -2 ±18 per hour for control P< 0.001), and lower norepinephrine levels (-1.03 ± 1.84 vs. 0.02 ± 0.99 nmol per liter, P=0.009).
Patients in the CPAP group also had significantly greater increases in mean nocturnal oxygen saturation (1.6 ± 2.8% vs. 0.4 ± 2.5 percent, P<0.001), LVEF (2.2 ± 5.4% vs. 0.4 ± 5.3 percent, P=0.02), and the distance walked in six minutes (20.0±55 vs. -0.8±64.8 m, P=0.016).
Despite these differences, however, there were no differences between the control group and the CPAP group in the number of hospitalizations, quality of life, or atrial natriuretic peptide levels.
“An early divergence in survival rates without heart transplantation favored the control group, but after 18 months the divergence favored the CPAP group, yet the overall event rates (death and heart transplantation) did not differ (32 vs. 32 events, respectively; P=0.54),” the authors wrote.
They noted that the trial was not large enough to determine whether the physiologic improvements they saw in the CPAP-treated patients could translate into a clinically important benefit.
Although their study “ultimately lacked the power to conclude with certainty that CPAP is ineffective in this patient population, our data do not support its routine use to extend life in patients with central sleep apnea and heart failure,” Bradley et al wrote.
“However, this recommendation may not be applicable to patients with heart failure who have obstructive sleep apnea, the pathophysiology of which, arising from pharyngeal occlusion, differs from that of central sleep apnea,” they concluded.
“Sleep occupies a third of our lives,” wrote Virend K. Somers, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., in an editorial accompanying the studies. “The cardiovascular implications of normal and disturbed sleep, and of sleep apnea in particular, have only recently gained prominence.”
He added, “Perhaps CPAP is simply not a viable therapeutic option for death-rate reduction in patients with heart failure, On the other hand, alternative approaches such as newer, more effective positive airway pressure devices, cardiac resynchronization therapy, and pharmacologic interventions may enable a more complete resolution of central sleep apnea and improved sleep quality and may conceivably translate into good outcomes.”
Primary source: New England Journal of Medicine
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