Oxygen Surges During Sleep May Mark the Heart Risk Hiding in Central Sleep Apnea

For decades, sleep scientists have focused most of their attention on the drops in oxygen that punctuate the nights of people with sleep apnea. Now a large new analysis suggests that the other half of the story — the rebound, the surge of oxygen that floods back when breathing resumes — may be just as important, and perhaps more so, for identifying which patients are truly in cardiovascular danger. In a study published in the Journal of Clinical Sleep Medicine, researchers report that a measure they call oxygen overshoot burden, the cumulative amount by which blood oxygen saturation rises above a person’s stable baseline during sleep, is strongly linked to major adverse cardiovascular events in people with central sleep apnea, but not in those with the far more common obstructive form of the disorder.

The finding comes from a team led by Ali Azarbarzin of Brigham and Women’s Hospital and Harvard Medical School, working with colleagues at several institutions, including Atul Malhotra of the University of California, San Diego. The researchers pooled data from two of the most extensively characterized sleep cohorts in the world: the Sleep Heart Health Study, which enrolled community-dwelling adults with an average age of 64, and the Osteoporotic Fractures in Men Study, known as MrOS, which followed older men with an average age of 76. Together the analysis included 7,530 participants, roughly 47 percent of whom were men in the combined framing of the two cohorts, each of whom had undergone overnight polysomnography with continuous pulse oximetry.

The technical concept at the heart of the study is deceptively simple. Every apnea episode, whether central or obstructive, produces a fall in oxygen saturation followed by a recovery. Conventional metrics such as the apnea-hypopnea index count how often these events occur, and more recent work has quantified the hypoxic burden, meaning the cumulative depth and duration of the desaturations themselves. Oxygen overshoot burden flips the perspective: it measures the area under the curve of oxygen saturation above baseline, capturing how far and how long the blood oxygen climbs back — and sometimes beyond — after each event. The researchers computed this overshoot against two reference points, a stable baseline recorded during sleep and, in secondary analyses, a baseline recorded during quiet wakefulness, to confirm that the signal was not an artifact of how the baseline was chosen.

Over a median follow-up of nearly nine years — 8.92 years — the cohorts recorded 2,258 major adverse cardiovascular events, a composite that captures the kind of outcomes that matter most to patients: heart attacks, heart failure episodes, strokes, and cardiovascular death. When the team modeled oxygen overshoot burden as a continuous variable, they found that higher burden was associated with increased cardiovascular risk across the population, but the association was markedly stronger among individuals who exhibited any central apneas during their sleep studies. The interaction was statistically significant for both the sleep baseline and the wakefulness baseline calculations, with p values of 0.003 and 0.02 respectively, suggesting the finding is robust to how the reference point is defined.

The most striking results emerged when the researchers stratified participants by diagnosis and by overshoot burden. People with central sleep apnea whose oxygen overshoot burden was at or above the cohort median experienced a dramatically elevated rate of cardiovascular events: 54.6 percent of them suffered a major adverse cardiovascular event during follow-up, compared with 25.6 percent of controls. After adjustment for a comprehensive set of covariates, the hazard ratio was 1.45, with a 95 percent confidence interval of 1.16 to 1.82 and a p value of 0.001. In contrast, three other groups showed cardiovascular risk that was statistically comparable to the controls: patients with central sleep apnea but low overshoot burden, and patients with obstructive sleep apnea whether their overshoot burden was high or low.

That last contrast is what makes the study potentially paradigm-shifting. Obstructive sleep apnea, caused by the physical collapse of the upper airway, and central sleep apnea, in which the brain temporarily stops sending the signals that drive breathing, have long been lumped together in clinical scoring systems that count respiratory events without much regard to their mechanism. Yet the new data suggest that the cardiovascular consequences of the two disorders may travel along different physiological paths, and that the overshoot of oxygen after each pause in breathing may be a signature of the central form that carries particular danger. The result held up even after the researchers adjusted for the apnea-hypopnea index, the central apnea index, loop gain — a measure of the instability of the respiratory control system — and the hypoxic burden, indicating that oxygen overshoot captures risk information that these established metrics do not.

The biological rationale for the finding lies in oxidative stress. Repeated cycles of deoxygenation and reoxygenation, known as intermittent hypoxia followed by reoxygenation, are thought to generate reactive oxygen species in much the same way that reperfusion injury damages tissue after a blocked artery is reopened. Animal studies dating back to the early 1990s have shown that episodic hypoxia elevates blood pressure and drives inflammation and atherosclerosis, and human studies have documented oxidative stress, endothelial dysfunction, and vascular inflammation in sleep apnea patients. The overshoot may be the moment when this chemistry is most active: as oxygen floods back into blood that has just been depleted, the surge could catalyze the oxidative bursts that injure the vessel wall. Central sleep apnea, which is especially prevalent in patients with heart failure and is associated with unstable respiratory control and high loop gain, may produce particularly pronounced or repetitive overshoots, creating a vicious cycle in which the breathing disorder and the heart disease feed each other.

The clinical implications are substantial. Central sleep apnea has been a stubborn therapeutic problem: large randomized trials of adaptive servo-ventilation and continuous positive airway pressure in heart failure patients have produced mixed or sobering results, and the field has increasingly recognized that not all patients with the same diagnosis carry the same risk. By identifying a high-risk phenotype — central apnea with high oxygen overshoot — the study offers a potential tool for stratifying patients in future trials, and it raises the possibility that therapies aimed specifically at blunting the overshoot, whether through oxygen titration, ventilatory support, or phrenic nerve stimulation, could be tested in the patients most likely to benefit. Recent trials of nocturnal oxygen therapy and transvenous phrenic nerve stimulation are already probing this territory, and overshoot burden could become an endpoint or an enrollment criterion in the next generation of studies.

The authors are careful to note the limitations. The two cohorts are older and, in the case of MrOS, exclusively male, so the findings need validation in larger and more diverse populations. Pulse oximetry itself carries a known bias across skin pigmentation, a concern highlighted by prior research showing that oximeters can overestimate oxygen saturation in people with darker skin, which could affect the precision of overshoot measurements. The study is observational, so it demonstrates association rather than causation, and residual confounding cannot be fully excluded. Still, the size of the cohorts, the length of follow-up, the consistency of the signal across baseline definitions, and the specificity of the effect to central apnea make the result one of the most compelling pieces of evidence yet that the aftermath of each apnea — not just the event itself — shapes cardiovascular fate.

For patients and clinicians, the message is that the texture of sleep-disordered breathing matters, not merely its frequency. A night of breathing pauses that end in modest, controlled recoveries of oxygen appears very different from one in which each pause is followed by a dramatic rebound, and the difference may separate a benign pattern from a dangerous one. As the field moves toward physiological phenotyping of sleep apnea, oxygen overshoot burden joins hypoxic burden and loop gain in a growing toolkit of quantitative measures that promise to replace blunt event counts with a more precise picture of what is actually happening in the blood, the brainstem, and the heart. The next step, the researchers say, is validation — and, ultimately, interventional trials that test whether taming the overshoot can tame the risk.

Subject of Research: Oxygen overshoot burden in central sleep apnea and its association with major adverse cardiovascular events

Article Title: Oxygen overshoot burden of central sleep apnea and its association with cardiovascular outcomes

Article References: Azarbarzin, A., McKane, S., Stone, K. L., 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, 22(1), Article 153. https://doi.org/10.1007/s44470-026-00161-0

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00161-0

Keywords: central sleep apnea, oxygen overshoot burden, cardiovascular outcomes, sleep-disordered breathing, oxidative stress, hypoxic burden, polysomnography, pulse oximetry, heart failure, intermittent hypoxia, risk stratification, Sleep Heart Health Study