Link strengthened between sleep apnea and mortality risk

Washington -- Evidence is building that sleep apnea poses an independent risk for dying, particularly from cardiovascular disease. Two studies in the Aug. 1 issue of the journal Sleep came to the same conclusion: Untreated obstructive sleep apnea can be lethal.

In addition, a joint statement from the American Heart Assn. and the American College of Cardiology, in recognition of this apparent connection between heart disease and sleep apnea, called for large-scale studies to determine possible mechanisms for this link.

The statement was published online July 28 in Circulation: The Journal of the American Heart Assn. and The Journal of the American College of Cardiology.

An estimated 12 million to 18 million Americans have moderate to severe sleep-disordered breathing, or sleep apnea, according to the National Heart Lung and Blood Institute. But since sleep apnea is strongly linked to obesity, the nation's collective weight gain may signal that even more people will be affected.

Obstructive sleep apnea involves a reduction in breathing, called hypopneas, or a complete halt in airflow, called apneas, during sleep. Most pauses last 10 to 30 seconds, but some may persist for one minute or longer, according to the American Academy of Sleep Medicine.

This condition can lead to abrupt reductions in blood oxygen saturation, with oxygen levels falling by 40% or more in severe cases.

In the larger of the two recent studies, people with severe sleep apnea had three times the risk of dying due to any cause compared with people who did not have sleep apnea. The researchers controlled for age, sex and body mass index. Additionally, when those who used continuous positive airway pressure therapy -- a first-line treatment for severe apnea -- were removed from the statistical analysis, the risk of dying was found to be four times greater among those with untreated apnea than for those without.

The study was part of an 18-year follow-up of 1,522 participants in the ongoing Wisconsin Sleep Cohort Study, which was established in 1988 and involved a random sample from the community. Participants were between the ages of 30 and 60 when the study began.

After spending one night at the University of Wisconsin School of Medicine and Public Health in Madison for assessment, participants were categorized by apnea-hypopnea index, or the average number of breathing pauses and reductions per hour of sleep. Sixty-three were found to have severe sleep apnea and about 1,157 had no apnea. The rest exhibited an intermediate range of apnea.

To follow up, state and national death records were reviewed to identify participants who had died and to note the cause of death on the death certificate. Eighty deaths were recorded, including 37 attributed to cancer and 25 attributed to cardiovascular disease. About 19% of participants with severe sleep apnea died, compared with about 4% of those with no sleep apnea.

Strong findings

"I was surprised by the strength of the risk," said lead researcher Terry Young, PhD, professor of epidemiology at the University of Wisconsin-Madison. "In epidemiology you rarely get such strong, robust findings. This strong association between sleep apnea and increased risk of all-cause mortality and cardiovascular risk was striking."

The second study in Sleep also found that moderate-to-severe sleep apnea was an independent risk factor for dying. Fourteen years after collecting initial data on sleep apnea for 380 men and women in the state of Western Australia, researchers found that about 33% of those with moderate to severe apnea had died, or six of 18 participants, compared with 7.7%, or 22 of the 285 without apnea.

"The size of the increased mortality risk was surprisingly large," said Nathaniel Marshall, PhD, a postdoctoral fellow at Australia's Woolcock Institute of Medical Research. "In our particular study a six-fold increase means that having significant sleep apnea at age 40 gives you about the same mortality risk as somebody aged 57 who doesn't have sleep apnea."

Michael Twery, PhD, director of the NHLBI's National Center on Sleep Disorder Research, wasn't surprised by the high mortality rates. "When people have difficulty getting air into their lungs it has an impact on their physical well-being," he noted. "We know that the desaturation of blood oxygen levels is a stressor."

What is yet unclear is how sleep apnea contributes to heart disease, said Virend Somers, MD, PhD, professor of medicine and cardiovascular diseases at Mayo Clinic and Mayo Foundation in Rochester, Minn. Dr. Somers chaired the writing committee for the AHA/ACC joint statement.

But despite this missing information, the cardiovascular community is concerned enough to recommend that treating apnea may also help prevent and treat heart disease.

This first step toward effective treatment also is likely to be taken by primary care physicians.

"Primary care is clearly where the action is," said Dr. Twery. However, recognizing and diagnosing patients with sleep apnea may be difficult. Physicians may want to pay more attention to those who complain of excessive daytime sleepiness. Sleep apnea may impair daytime vigilance, he added.

Individualizing treatment is important, said Dr. Somers. Among those patients at the top of the list are heavy snorers and those who have been told they stop breathing at night.

Patients who have cardiovascular disease, high blood pressure, heart failure or atrial fibrillation, and those who are obese or snore may also have sleep apnea. And the disorder should be considered among patients with cardiovascular disease who don't respond well to standard therapy. "This suggests there is something going on in the disease process that we are not treating," Dr. Somers said.