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WHILE
YOU WERE SLEEPING: SLEEP-DISORDERED BREATHING SYNDROMES INCREASE STROKE RISK
SALT LAKE CITY—Sleep-disordered breathing appears to profoundly affect stroke risk and outcomes, reported Vahid Mohsenin, MD, at the 20th Anniversary Meeting of the Associated Professional Sleep Societies.
Among patients with ischemic stroke, stroke incidence is substantially increased between midnight and noon, pointed out Dr. Mohsenin, Director of the Yale Center for Sleep Medicine in New Haven. By contrast, hemorrhagic stroke risk remains relatively flat over 24 hours, he said.
In 2005, Dr. Mohsenin and colleagues investigated the relationship between sleep-disordered breathing and stroke. Of the 1,022 individuals enrolled in their study, 697 (68%) had obstructive sleep apnea (an apnea-hypopnea index of 5 or higher). The sleep apnea group had a mean apnea-hypopnea index of 35 at baseline versus only 2 for the comparison group of patients without obstructive sleep apnea.
The researchers associated obstructive sleep apnea with a hazard ratio of 2.24 for stroke or death from any cause. After adjustment for age, sex, race, smoking status, alcohol consumption, BMI, and the presence or absence of diabetes, hyperlipidemia, atrial fibrillation, or hypertension, the hazard ratio was still significantly elevated at 1.97. "But you cannot really conclude [from these data] that there might be a causation," acknowledged Dr. Mohsenin.
Dr. Mohsenin also highlighted the results of the 2001 Sleep Heart Health Study, in which investigators examined the cross-sectional relationship between sleep-disordered breathing and self-reported cardiovascular disease among 6,424 individuals. Overnight polysomnography confirmed that mild to moderate sleep-disordered breathing was highly prevalent in this population, as indicated by a median apnea-hypopnea index of 4.4.
Sixteen percent of these individuals reported at least one manifestation of cardiovascular disease, such as myocardial infarction, angina, heart failure, stroke, or the need for coronary revascularization. In the highest quartile of apnea-hypopnea indexes, the relative risk of heart failure, stroke, and coronary artery disease was 2.38 compared to 1.27 in the lowest quartile.
IS SLEEP APNEA A CAUSE?
"We have reason to believe that sleep apnea can potentially cause stroke," said Dr. Mohsenin, explaining that there are numerous plausible mechanisms for a cause-effect relationship between obstructive sleep apnea and stroke. For instance, the decreased cardiac output seen in sleep apnea could set up the patient for a stroke by reducing cerebral perfusion, he suggested. Apnea-induced hypercapnia might precipitate a stroke by increasing intracranial pressure.
Furthermore, hypertension, a major stroke risk factor, is common in sleep apnea. It has also been suggested that obstructive sleep apnea may cause stroke by promoting atherosclerosis and hypercoagulability, altering cerebral autoregulation, and impairing endothelial function.
Several studies support an independent cause-effect relationship between sleep apnea and stroke. In 2000, investigators observed that obstructive apneas and hypopneas remained unchanged after stroke even when patients recovered from their stroke-related neurologic deficits. This finding suggests that obstructive sleep apnea was present prior to the occurrence of stroke, Dr. Mohsenin reasoned.
Similarly, a 2002 study of ischemic stroke patients found no significant difference in the oxygen desaturation index (a substitute for the apnea-hypopnea index) in the acute phase of stroke versus the recovery phase. The oxygen desaturation index did improve during the recovery phase in hemorrhagic stroke patients, however.
Most recently, Munoz et al performed a prospective, longitudinal study in a population of elderly subjects (ages 70 to 100) and found that severe obstructive sleep apnea (apnea-hypopnea index of 30 or greater) increased the risk of ischemic stroke independently of confounding variables.
WORSE POSTSTROKE SURVIVAL
Sleep-disordered breathing syndromes such as sleep apnea appear to compromise survival following a stroke, emphasized Dr. Mohsenin. Among the studies to support that conclusion was an investigation by Parra and colleagues in 2004 of 161 elderly patients who had a stroke or transient ischemic attack.
In that population, multivariate analysis independently associated the apnea-hypopnea index with mortality; age, involvement of the middle cerebral artery, and the presence of coronary disease showed similar relationships to patient survival. The investigators concluded that sleep-related breathing disorders predict mortality after a first episode of stroke.
Subsequently, Bassetti et al evaluated the effect of sleep-disordered breathing on the outcomes of 152 patients during the first six months after acute ischemic stroke (the subacute phase) and an average of five years poststroke. The patients had a mean apnea-hypopnea index of 18 initially, and this fell significantly during the subacute phase.
Older age, male gender, a high BMI, diabetes, hypertension, coronary heart disease, a poor score on the Epworth Sleepiness Scale, and macroangiopathic etiology of stroke were significantly more common in patients with an apnea-hypopnea index of 30 or greater than in those with an apnea-hypopnea index of less than 10. Also, long-term stroke mortality was associated with the initial apnea-hypopnea index as well as with age, hypertension, diabetes, and coronary heart disease.
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—Timothy Begany
Suggested Reading
Bassetti CL, Milanova M, Gugger M. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke. 2006;37:967-972.
Elwood P, Hack M, Pickering J, et al. Sleep disturbance, stroke, and heart disease events: evidence from the Caerphilly cohort. J Epidemiol Community Health. 2006;60:69-73.
Martinez-Garcia MA, Galiano-Blancart R, Roman-Sanchez P, et al. Continuous positive airway pressure treatment in sleep apnea prevents new vascular events after ischemic stroke. Chest. 2005;128:2123-2129.
Munoz R, Duran-Cantolla J, Martinez-Vila E, et al. Severe sleep apnea and risk of ischemic stroke in the elderly. Stroke. 2006;37:2317-2321.
Newman AB, Nieto FJ, Guidry U, et al. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol. 2001;154:50-59.
Parra O, Arboix A, Montserrat JM, et al. Sleep-related breathing disorders: impact on mortality of cerebrovascular disease. Eur Respir J. 2004;24:267-272.
Yaggi HK, Concato J, Kernan WN, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034-2041.
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