Apnea-Hypopnea Event Duration Predicts Mortality in Men and Women in the Sleep Heart Health Study.

RATIONALE: Obstructive sleep apnea is a risk factor for mortality, but its diagnostic metric-the apnea-hypopnea index-is a poor risk predictor. This apnea-hypopnea index does not capture the range of physiological variability within and between patients, such as degree of hypoxemia and sleep fragmentation, that reflect differences in pathophysiological contributions of airway collapsibility, chemoreceptive negative feedback loop gain, and arousal threshold.

OBJECTIVE: To test whether respiratory event duration, a heritable sleep apnea trait reflective of arousal threshold, predicts all-cause mortality.

METHODS: Mortality risk as a function of event duration was estimated by Cox proportional hazards in the Sleep Heart Health Study, a prospective community-based cohort. Gender-specific hazard ratios were also calculated.

MEASUREMENTS AND MAIN RESULTS: Among 5712 participants, 1290 deaths occurred over 11 years of follow-up. After adjusting for demographic factors (mean age 63 years old; 52% female), apnea-hypopnea index (mean 13.8; standard deviation 15.0), smoking, and prevalent cardio-metabolic disease, individuals with the shortest duration events had a significant hazard ratio for all-cause mortality of 1.31 [95% confidence interval: 1.11-1.54]. This relationship was observed in both men and women and was strongest in those with moderate sleep apnea (hazard ratio = 1.59 [1.11-2.28]).

CONCLUSIONS: Short respiratory event duration, a marker for low arousal threshold, predicts mortality in men and women. 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.