Mild to Moderate Sleep Apnea Increases Stroke Risk

Janis C. Kelly

April 15, 2010

April 15, 2010 — Data from the Sleep Heart Health Study show that even moderate levels of sleep apnea carry significant risk for stroke for men and that severe sleep apnea can also increase stroke risk for women.

This study, led by Susan Redline, MD, MPH, of Case Western Reserve University in Cleveland, Ohio, is the first to establish a link between obstructive sleep apnea (OSA) and ischemic stroke in a community-based sample of men and women across a wide range of sleep apnea.

It was published online March 25 in the American Journal of Respiratory and Critical Care Medicine.

The study authors report that men with the most severe OSA were twice as likely to have a stroke as men in the quartile with the least severe OSA during a median 8.7 years of follow-up.

"Our findings provide compelling evidence that obstructive sleep apnea is a risk factor for stroke, especially in men," Dr. Redline said. "Overall, the increased risk of stroke in men with sleep apnea is comparable to adding 10 years to a man’s age. Importantly, we found that increased stroke risk in men occurs even with relatively mild levels of sleep apnea."

Common Disorder

OSA is a common disorder in which the upper airway is intermittently narrowed or blocked, disrupting sleep and breathing during sleep.

The Sleep Heart Health Study was the first to find a link between sleep apnea and increased risk for stroke in women. It was conducted in 9 medical centers across the United States and included 5422 participants 40 years and older without a history of stroke at study entry. All patients had baseline polysomnography at home, were assessed with the obstructive apnea hypopnea index (OAHI), and were followed up for a median of 8.7 years.

During this period, 193 participants had a stroke: 85 of 2462 men and 108 of 2960 women. After adjusting for several cardiovascular risk factors, the researchers found that the effect of sleep apnea on stroke risk was stronger in men than in women.

In men, a progressive increase in stroke risk was observed as sleep apnea severity increased from mild levels (baseline OAHI, 5) to moderate to severe levels (OAHI, 25). The risk for stroke increased 6% with every unit increase in baseline OAHI. In women, however, the increased risk for stroke was significant only with severe levels of sleep apnea (OAHI, 25).

Men in the highest OAHI quartile (>19) were nearly 3 times more likely to have a stroke than men without sleep apnea or with mild sleep apnea (adjusted hazard ratio, 2.86; 95% confidence interval, 1.1 – 7.4). The was independent of other risk factors, such as weight, high blood pressure, race, smoking, and diabetes.

For women, stroke risk was not significantly associated with OAHI quartiles, but an increased risk was seen with severe apnea (OAHI, >25).

The researchers suggest that the differences between men and women might be because men are more likely to develop sleep apnea at younger ages and so tend to have untreated sleep apnea for longer periods than women. "It’s possible that the stroke risk is related to cumulative effects of sleep apnea adversely influencing health over many years," said Dr. Redline.

The new results support earlier findings that have linked sleep apnea to stroke risk (Stroke. 2006;37:2317-2321; Am J Respir Crit Care Med. 2005;172:1447-1451).

Unexpected Observation

An unexpected observation in this study was that greater numbers of cortical arousals per hour of sleep were associated in women with lower risk for stroke. Women who had an arousal index greater than 12 had a 40% to 60% lower hazard rate for ischemic stroke than women with a lower arousal index. Benzodiazepines, which reduce arousal frequency, also increased stroke risk in women.

According to Dr. Redline, the next logical step is to determine whether treating sleep apnea can lower a person’s risk for these leading killers. The researchers will conduct the first National Institutes of Health–funded comparative effectiveness study of treatments for sleep apnea. The 2-year multicenter pilot study will compare the cardiovascular effects of adding either continuous positive airway pressure or supplemental oxygen during sleep to standard care in patients with moderate to severe sleep apnea who are at high risk for cardiovascular disease events, including myocardial infarction and stroke.

Dr. Redline told Medscape Neurology that that study began recruiting patients in January and has randomized about 25 patients to date. "We will continue recruitment through April 2011. We hope to screen about 1400 patients, randomizing 360 and following each for 3 months for intermediate markers of cardiovascular disease," Dr. Redline said. The primary endpoint is 24-hour blood pressure.

Strong Evidence

John Heffner, MD, past president of the American Thoracic Society, said in a statement, "We now have strong evidence from this study that obstructive sleep apnea increases stroke risk directly. But we also have emerging evidence from other studies that sleep apnea may further increase stroke risk by causing, or at least accelerating, other diseases, such as diabetes, that contribute to cerebrovascular disease.

"The importance of diagnosing and treating obstructive sleep apnea requires greater emphasis in general clinical practice, considering it is still underrecognized by primary care physicians," he adds.

"Although scientists have uncovered several risk factors for stroke, such as age, high blood pressure and atrial fibrillation, and diabetes, there are still many cases in which the cause or contributing factors are unknown," said National Heart, Lung, and Blood Institute acting director Susan B. Shurin, MD, in a statement.

"This is the largest study to date to link sleep apnea with an increased risk of stroke. The time is right for researchers to study whether treating sleep apnea could prevent or delay stroke in some individuals."

This study was supported by the National Heart, Lung, and Blood Institute. Dr. Redline has disclosed no relevant financial relationships.

Am J Respir Crit Care Med. Published online March 25, 2010.

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