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

Abstract

<b>Rationale:</b> The apnea-hypopnea index (AHI), used for the diagnosis of obstructive sleep apnea, captures only the frequency of respiratory events and has demonstrable limitations. <b>Objectives:</b> We propose a novel automated measure, termed "ventilatory burden" (VB), that represents the proportion of overnight breaths with less than 50% normalized amplitude, and we show its ability to overcome limitations of AHI. <b>Methods:</b> Data from two epidemiological cohorts (EPISONO [Sao Paolo Epidemiological Study] and SHHS [Sleep Heart Health Study]) and two retrospective clinical cohorts (DAYFUN; New York University Center for Brain Health) were used in this study to <i>1</i>) derive the normative range of VB, <i>2</i>) assess the relationship between degree of upper airway obstruction and VB, and <i>3</i>) assess the relationship between VB and all-cause and cardiovascular disease (CVD) mortality with and without hypoxic burden that was derived using an in-house automated algorithm. <b>Measurements and Main Results:</b> The 95th percentiles of VB in asymptomatic healthy subjects across the EPISONO and the DAYFUN cohorts were 25.2% and 26.7%, respectively (median [interquartile range], VB_EPISONO, 5.5 [3.5-9.7]%; VB_DAYFUN, 9.8 [6.4-15.6]%). VB was associated with the degree of upper airway obstruction in a dose-response manner (VB_untreated, 31.6 [27.1]%; VB_treated, 7.2 [4.7]%; VB_{suboptimally treated}, 17.6 [18.7]%; VB_{off-treatment}, 41.6 [18.1]%) and exhibited low night-to-night variability (intraclass correlation coefficient [2,1], 0.89). VB was predictive of all-cause and CVD mortality in the SHHS cohort before and after adjusting for covariates including hypoxic burden. Although AHI was predictive of all-cause mortality, it was not associated with CVD mortality in the SHHS cohort. <b>Conclusions:</b> Automated VB can effectively assess obstructive sleep apnea severity, is predictive of all-cause and CVD mortality, and may be a viable alternative to the AHI.