Oxygen overshoot burden in CSA is independently associated with increased MACE risk and may improve risk stratification in sleep-disordered breathing.
Key Findings
Results
Greater oxygen overshoot burden (continuous) was associated with increased MACE risk, with stronger associations among individuals with any central apneas.
Interaction p-values were p=0.003 and p=0.02 for sleep and wakefulness baselines, respectively
Oxygen overshoot burden was defined as the area under the SpO2 curve above a stable sleep baseline (wakefulness baseline was also considered as an alternative)
Cox proportional hazards models were used, adjusted for covariates
Analysis included 7,530 participants from two cohorts: SHHS (age 64 years, 47.0% male) and MrOS (age 76 years, 100% male)
Results
Participants with CSA and high oxygen overshoot burden had significantly higher MACE incidence compared to controls.
MACE incidence was 54.6% in CSA with high oxygen overshoot burden versus 25.6% in controls
HR 1.45 (95% CI = 1.16, 1.82); p=0.001
High oxygen overshoot burden was defined as at or above the median value
Over a follow-up of 8.92 years, 2,258 MACE events occurred across the full sample
Results
CSA with low oxygen overshoot burden was not associated with elevated MACE risk compared to controls.
Participants with CSA and low oxygen overshoot burden showed MACE risk comparable to controls
This contrasts with the CSA high oxygen overshoot burden group (HR 1.45)
Low oxygen overshoot burden was defined as below the median value
Results
OSA with either high or low oxygen overshoot burden was not associated with elevated MACE risk compared to controls.
Both OSA subgroups (high and low oxygen overshoot burden) showed MACE risk comparable to controls
This finding distinguishes the cardiovascular risk profile of CSA from OSA in the context of oxygen overshoot
Participants were classified as having CSA, OSA, or no sleep apnea in secondary analyses
Results
The association between oxygen overshoot burden and MACE in CSA was robust to adjustment for multiple sleep apnea metrics.
Results remained significant after adjustment for apnea-hypopnea index (AHI), central apnea index, loop gain, and hypoxic burden
This suggests oxygen overshoot burden provides independent prognostic information beyond established sleep apnea severity measures
Discussion
The study identified potential limitations related to sample characteristics and pulse oximetry bias across skin pigmentation.
Authors noted that findings require validation in larger, more diverse populations
Potential pulse oximetry bias across skin pigmentation was acknowledged as a limitation
The MrOS cohort was 100% male and the SHHS cohort was 47.0% male, limiting generalizability
What This Means
This research suggests that a newly characterized sleep measurement called 'oxygen overshoot burden' — which captures how much a person's blood oxygen level rises above their normal baseline after breathing disruptions during sleep — is linked to a significantly higher risk of serious cardiovascular events (such as heart attacks and strokes) specifically in people with central sleep apnea (CSA). The study analyzed over 7,500 adults from two large population studies and tracked cardiovascular events over nearly nine years. People with CSA who had high oxygen overshoot burden experienced major cardiovascular events at a rate of about 55%, compared to about 26% in people without sleep apnea, representing a 45% higher relative risk.
Importantly, this elevated risk was specific to central sleep apnea — people with obstructive sleep apnea (OSA) did not show the same pattern, regardless of their oxygen overshoot levels. Even among people with CSA, those with low oxygen overshoot burden did not have elevated cardiovascular risk. This suggests that oxygen overshoot burden could help identify a particularly high-risk subgroup within CSA patients. The association held up even after accounting for other established measures of sleep apnea severity, suggesting it captures something unique about cardiovascular risk.
This research suggests that the temporary spikes in blood oxygen that follow breathing pauses in CSA — potentially reflecting oxidative stress — may play a role in damaging the cardiovascular system. Oxygen overshoot burden could potentially be used to better identify which CSA patients are at the greatest cardiovascular risk. However, the authors caution that these findings need to be validated in larger and more diverse populations, and that standard pulse oximetry devices may not measure oxygen levels equally accurately across people with different skin tones, which could affect the results.
Azarbarzin A, McKane S, Stone K, Germany R, Redline S, Malhotra A. (2026). Oxygen overshoot burden of central sleep apnea and its association with cardiovascular outcomes.. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. https://doi.org/10.1007/s44470-026-00161-0