C100-04 Hyperoxic Burden of Central Sleep Apnea and Its Association With Cardiovascular Outcomes

Rationale The role of reoxygenation following respiratory events in central sleep apnea (CSA) remains unclear. We examined whether “hyperoxic burden”—a novel measure of cumulative oxygen levels above baseline during sleep—is associated with major adverse cardiovascular events (MACE) in individuals with CSA. Methods We analyzed 7,530 participants from the Sleep Heart Health Study (SHHS; median age 64 years; 2568 females, 2273 males) and the Osteoporotic Fractures in Men study (MrOS; median age 76 years; 2689 males). Hyperoxic burden was defined as the area under the SpO2 curve above a stable sleep baseline (Figure 1 (A)). Participants were classified as no sleep apnea (controls; AHI<15 events/h and central apnea index[CAI] < 5 events/h), having CSA (AHI≥15 and CAI≥5 events/h), or obstructive sleep apnea (OSA; AHI≥15 and CAI<5 events/h), with further classication of OSA and CSA groups by high versus low hyperoxic burden based on median value. Cox proportional hazard models adjusted for demographic and clinical covariates were used to estimate hazard ratios (HRs) for MACE. Covariates included age, sex, race, body mass index, hypertension, diabetes, smoking status, and prevalent heart failure, myocardial infarction, and stroke. Results Over 8.92 years of follow-up, 2,258 MACE events occurred. Individuals with CSA and high hyperoxic burden had significantly higher MACE incidence (54.6%) compared to controls (25.6%) with an adjusted HR of 1.45 (95% CI: 1.16-1.82; p = 0.001; Figure 1 (B)). Comparison between individuals with CSA and low hyperoxic burden and controls showed no significant increase in MACE risk (HR: 1.09 [0.84-1.42], p = 0.450). Similarly, individuals with OSA, whether with high (HR: 1.04 [0.91, 1.18], p = 0.578) or low (HR: 1.03 [0.94, 1.14], p = 0.535) hyperoxic burden, exhibited MACE rates comparable to those of controls. When modeled continuously, hyperoxic burden showed a dose-response relationship with MACE across the entire cohort, driven primarily by findings in the CSA subgroup; findings remained consistent after adjusting for AHI, central apnea index, loop gain, and hypoxic burden. Conclusions Our findings suggest that hyperoxic burden is a novel marker of cardiovascular risk in individuals with CSA. Further studies are needed to elucidate the underlying mechanisms—such as ventilatory control instability, oxidative stress, and/or underlying cardiopulmonary disease—that may link CSA-related hyperoxic burden to adverse outcomes. These findings may have clinical implications and could inform risk stratification in future clinical trials.