Journal Article Epublish 1 citation
PubMed: 42675346 DOI: 10.1007/s44470-026-00161-0
Oxygen overshoot burden of central sleep apnea and its association with cardiovascular outcomes.
J Clin Sleep Med 22(1)
Authors: Ali Azarbarzin, Scott McKane, Katie L Stone, Robin Germany, Susan Redline, Atul Malhotra
Affiliations
- Division of Sleep and Circadian Disorders, Brigham and Hospital and Harvard Medical School, Boston, MA, USA.
- Sleep Apnea Health Outcomes Research Group, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA, 02115, USA.
- ZOLL Respicardia, Inc. Minnetonka, MN, USA.
- Research Institute, California Pacific Medical Center, San Francisco, CA, USA.
- Division of Sleep and Circadian Disorders, Brigham and Hospital and Harvard Medical School, Boston, MA, USA.
- Division of Pulmonary, Critical Care, Sleep Medicine and Physiology, San Diego (UCSD), University of California, La Jolla, CA, USA.
Abstract
PURPOSE
The role of oxidative stress in central sleep apnea (CSA) remains unknown. We examined whether "oxygen overshoot burden"-a measure of cumulative oxygen saturation levels above baseline-is associated with major adverse cardiovascular events (MACE) in CSA.
METHODS
We analyzed 7530 participants from the Sleep Heart Health Study (SHHS; age 64 years; 47.0% male) and the Osteoporotic Fractures in Men Study (MrOS; age 76 years; 100% male). Oxygen overshoot burden was defined as the area under the SpO 2 curve above a stable sleep baseline (wakefulness baseline was also considered). In primary analysis, oxygen overshoot burden was modeled continuously. In secondary analyses, participants were classified as having CSA, obstructive sleep apnea (OSA), or no sleep apnea, and stratified by high (≥ median) versus low oxygen overshoot burden. Cox models adjusted for covariates were used to estimate hazard ratios (HRs) for MACE.
RESULTS
Over a follow-up of 8.92 years, 2258 MACE events occurred. Oxygen overshoot burden (continuous) was associated with increased MACE risk, with stronger associations among individuals with any central apneas (p = 0.003 and p = 0.02 for sleep and wakefulness baselines, respectively). In secondary analyses, participants with CSA and high oxygen overshoot burden had higher MACE incidence (54.6%) than controls (25.6%; HR 1.45 [95%CI = 1.16,1.82]; p = 0.001). In contrast, CSA with low oxygen overshoot burden and OSA with high or low oxygen overshoot burden showed MACE risk comparable to controls. Results were robust to adjustment for AHI, central apnea index, loop gain, and hypoxic burden.
CONCLUSIONS
Oxygen overshoot burden in CSA is independently associated with increased MACE risk and may improve risk stratification in sleep-disordered breathing. These findings require validation in larger, more diverse populations given sample limitations and potential pulse oximetry bias across skin pigmentation.
CURRENT KNOWLEDGE/STUDY RATIONALE
Oxidative stress may contribute to cardiovascular risk in central sleep apnea (CSA), but the clinical significance of post-apneic oxygen overshoot is unknown. We examined whether oxygen overshoot burden, representing cumulative oxygen saturation above baseline, is associated with major adverse cardiovascular events (MACE).
STUDY IMPACT
Greater oxygen overshoot burden was associated with increased cardiovascular risk in individuals with central sleep apnea but not in those with obstructive sleep apnea. These findings identify a potential high-risk central sleep apnea phenotype and suggest that oxygen overshoot burden may improve cardiovascular risk stratification and inform future mechanistic and interventional studies.
MeSH
Sleep Apnea, Obstructive, Sleep, Wakefulness, Stress, Physiological, Apnea, Sleep Apnea, Central, Sleep Apnea Syndromes, Oxygen Saturation