Duration of Disturbed Breathing During Sleep Predicts Mortality

How long a person with obstructive sleep apnea (OSA) stops breathing may be a better predictor of mortality risk from OSA in both women and men than the number of times they stop breathing, a new study published in the American Journal of Respiratory and Critical Care Medicine concludes.¹

Study participants who had short apneas (stopped breaths) and hypopnea (shallow breaths) were at greater risk of dying over a decade of follow up than those who had long apneas—a counterintuitive conclusion because one would expect longer periods of not breathing to be more severe. But shorter periods of disturbed breathing indicate a low arousal threshold, said study author Matthew P. Butler, PhD, which would be associated with sleep fragmentation, elevated sympathetic tone, and greater risk for hypertension.

Researchers set out to test whether respiratory event duration, a heritable sleep apnea trait reflective of arousal threshold, predicts all-cause mortality. The apnea—hypopnea index (AHI) is the most widely used diagnostic metric for OSA and has been shown to predict mortality risk in some, but not all studies; however, it is a poor predictor of risk and does not capture the range of physiologic variability within and between patients that reflect differences in pathophysiological contributions of airway collapsibility, chemoreceptive negative feedback loop gain, and arousal threshold. It is also not a good predictor for women, the investigators wrote.

The researchers analyzed the records of 5712 adults (average age, 63) who participated in the Sleep Heart Health Study, a prospective community-based cohort sponsored by the National Heart, Lung, and Blood Institute. The study enrolled approximately the same number of men and women and followed them for up to 11 years.

• There were 1290 deaths during follow-up.
• After adjusting for demographic factors, AHI (mean, 13.8; standard deviation, 15.0), smoking, and prevalent cardiometabolic disease, individuals with the shortest-duration events were 31% more likely to die compared with those who had longer duration of breaths.
• The association was strongest in study participants with moderate sleep apnea as measured by the AHI. In this group, participants with the shortest duration of breathing events had a 59% increased risk of dying.

The researchers said their analysis shows that short event duration predicts all-cause mortality over, beyond that predicted by the AHI, in both men and women. Additionally, the duration of abnormal breathing events is easily measured in polysomnography studies—the same studies that patients now undergo to measure AHI—and may help identify subgroups with low arousal threshold who are at risk for adverse outcomes. The researchers say their findings suggest a genetically encoded phenotype of OSA, which agrees with previous studies that have shown that duration of breathing events is highly heritable and that shorter abnormal breathing events are more common in women and African Americans.

Individuals with shorter respiratory events may be predisposed to increased ventilatory instability and/or have augmented autonomic nervous system responses that increase the likelihood of adverse health outcomes, underscoring the importance of assessing physiological variation in obstructive sleep apnea.

The investigators note an important study limitation. Because it was not a randomized controlled trial, the study could not determine causality between shorter events and death. Shorter events may be a marker for underlying problems that result in increased deaths, rather than the cause itself.

“This study shows that a readily available trait that is usually not analyzed—the duration of respiratory disturbances—predicts mortality over and beyond that predicted by AHI in both women and men,” Butler concluded. “Further research is needed to determine how OSA and a low arousal threshold interact as a health risk.”

Reference

Butler MP, Emch JR, Rueschman M, et al. Apnea-hypopnea event duration predicts mortality in men and women in the Sleep Heart Health Study [published online October 19, 2018]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201804-0758OC.