Delayed Arousal Response to Sleep Apnea Encodes Mortality
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Rationale
Conventional measures of obstructive sleep apnea severity, particularly the apnea-hypopnea index, do not adequately capture event-level neurophysiologic responses to respiratory events. Whether post-apnea/hypopnea arousal dynamics provide prognostic information beyond established metrics remains unknown.
Objectives
To determine whether post-apnea/hypopnea arousal dynamics are associated with all-cause and cardiovascular mortality.
Methods
We conducted a retrospective analysis of in-home polysomnography data from 8,053 adults across four community-based cohorts. Peak time (PT; latency to maximal arousal probability), peak height (PH; maximal arousal probability), and area under the curve (AUC; cumulative arousal probability) were derived from peri-stimulus time histograms aligned to event termination. Associations with mortality were examined using multivariable Cox models and random-effects meta-analysis.
Measurements and Main Results
PT, but not PH or AUC, was associated with mortality. In pooled analyses, each 1-second delay in PT was associated with higher all-cause mortality in males (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02–1.06) and females (HR, 1.03; 95% CI, 1.00–1.06). For cardiovascular mortality, each 1-second delay in PT was associated with higher risk in males (HR, 1.05; 95% CI, 1.02–1.08) but not females (HR, 1.04; 95% CI, 0.99–1.10). Associations were driven primarily by non-rapid eye movement sleep and remained materially unchanged after additional adjustment for apnea-hypopnea index, arousal index, and hypoxic burden.
Conclusions
Delayed arousal timing after apnea/hypopnea termination was associated with increased mortality risk independent of conventional measures of obstructive sleep apnea severity. Event-level arousal timing may provide prognostic information beyond count-based and hypoxemia-based metrics.
