Ventilatory Burden as a Measure of Obstructive Sleep Apnea Severity Is Predictive of Cardiovascular and All-Cause Mortality

Rationale: Apnea-hypopnea index (AHI) used for the diagnosis of obstructive sleep apnea (OSA) captures only the frequency of respiratory events and has demonstrable limitations. Objective: We propose a novel automated measure termed ventilatory burden (VB) that represents the proportion of overnight breaths with less than 50% normalized amplitude and show its ability to overcome limitations of AHI. Methods: Data from two epidemiological cohorts (Sao Paolo Epidemiological Study (EPISONO), and Sleep Heart Health Study (SHHS)) and two retrospective clinical cohorts (DAYFUN; NYU Center for Brain Health), were used in this study to a) derive the normative range of VB, b) asses the relationship between degree of upper airway obstruction and VB, and c) assess the relationship between VB and all-cause and cardiovascular (CVD) mortality with and without hypoxic burden (HB) that was derived using an in-house automated algorithm. Results: The 95th percentile of VB in asymptomatic healthy subjects across the EPISONO and the DAYFUN cohorts was 25.2% and 26.7% respectively (VBEPISONO=5.5[3.5-9.7]%, VBDAYFUN=9.8[6.4-15.6]%; median[interquartile range]). VB was associated with the degree of upper airway obstruction in a dose-response manner (VBuntreated=31.6(27.1)%, VBtreated=7.2(4.7)%, VBsuboptimally-treated=17.6(18.7)%, VBoff-treatment=41.6(18.1)%) and exhibited low night-to-night variability (ICC[2,1]=0.89). VB was predictive of all-cause and CVD mortality in the SHHS cohort, before and after adjusting for covariates including HB. While AHI was predictive of all-cause mortality, it was not associated with CVD mortality in SHHS cohort. Conclusion: Automated ventilatory burden can effectively assess OSA severity, is predictive of all-cause and CVD mortality, and may be a viable alternative to the AHI.