By Lisa Spear

Let’s think of the apnea. The gasp for air in the middle of the night. The choking apnea when the tongue slips into the back of the throat. The rhythmic snore that gets louder until punctuated by a snort as blood oxygen levels dip. All these breathing disruptions, despite the potential variations in their depth of oxygen desaturation, are counted the same by the apnea-hypopnea index (AHI), the gold standard metric for diagnosing and measuring the severity of obstructive sleep apnea (OSA). 

AHI Versus Hypoxic Burden

While the AHI remains a useful metric, it doesn’t paint the full picture of how and if OSA could contribute, for instance, to a stroke or heart failure, or if the condition will simply lead to daytime sleepiness, says John E. Remmers, MD, chief scientist for ProSomnus Sleep Technologies. “It doesn’t tell you how bad the sleep apnea is, it just tells you how much is there,” he says.

One relatively new metric called the sleep apnea-specific hypoxic burden could disrupt how sleep specialists think about apneas. Developed by researchers at Harvard Medical School, the hypoxic burden measures how much blood oxygen levels decrease during sleep and how long they stay down after a disruption in breathing.¹ It is calculated based on the number of events and the time spent below a patient-specific baseline during sleep. However, various definitions and calculations can be used.² While few diagnostic companies have released software that automatically calculates the hypoxic burden, the metric is gaining some ground as awareness spreads.

“Hypoxic burden, I agree, is a great metric,” says Amir Reuveny, PhD, CEO of Wesper, a sleep diagnostics company that produces one of the only home sleep tests that auto-calculates hypoxic burden. He sees hypoxic burden as working with other metrics, like AHI, respiratory effort, and others, to tell the full story of the patient’s sleep health.

The hypoxic burden can evaluate, in terms of low blood oxygen levels, how detrimental sleep apnea is, and there is evidence that it is a better marker than AHI for evaluating cardiovascular risk in OSA patients.¹

A recent abstract presented at the American Thoracic Society International conference showed that hypoxic burden, but not AHI, predicts the risk of major cardiovascular and cerebrovascular adverse outcomes in untreated OSA or patients who were not adherent to PAP therapy.³ 

Hypoxic Burden and Oral Appliances

Sat Sharma, MD, FRCPC, FCCP, FACP, FAASM, medical director of the Centre for Sleep and Chronobiology and chief medical officer of Open Airway Dental Solutions, and colleagues won the American Academy of Dental Sleep Medicine Clinical Research Award in 2024 for a study that showed efficacy of an oral appliance-expiratory positive airway pressure combination therapy to be 94% using hypoxic burden criteria, as compared to 72% by AHI reduction criteria. The abstracts suggests that AHI “misclassified a substantial number of individuals” who truly responded to the therapy.⁴

Another paper, for which ProSomnus’ Remmers is an author, showed that an oral appliance reduced the hypoxic burden by 95%—whereas it reduced the AHI by 75%. The authors point out a particularly noteworthy reduction in hypoxic burden in severe OSA, where the median hypoxic burden for oral appliance users decreased from 103.8%min/h to 16.5 %min/h.⁵ 

Results like these call into question whether it might be appropriate to substitute hypoxic burden, or use it in conjunction with AHI, when evaluating the efficacy of oral appliance therapy. This change would increase the number of patients who are considered responders, particularly in the severe OSA group.

“I think hypoxic burden is particularly useful in therapies like oral appliance therapy that…leave the patients with some sleep apnea,” Remmers says.

“CPAP can almost always eliminate apneas by increasing pressure,” says Keith Thornton, DDS, CEO and chief technology officer at AirWay Technologies Inc. “Obesity and ultimate limitation on the protrusive range of motion of a mandible limits [oral appliance] efficacy in the more severe patients. The use of hypoxic burden would be better for the patient and the profession since it has a better possibility of being the gold standard for [cardiovascular disease] in sleep apnea than is AHI.”

Where Could Hypoxic Burden Fit?

Still, many agree that more research needs to be done to fully understand the hypoxic burden’s role in measuring patient outcomes. While promising, the predictive power of hypoxic burden for individual treatment response, particularly with oral appliances, is still being explored. The current research suggests that it may not be sufficient for making individual treatment decisions, Sharma says.

Most agree that we have a long way to go before hypoxic burden becomes mainstream, and it may never dethrone AHI. Despite this, Sharma says, hypoxic burden has great potential and fills in places where AHI falls short. For example, the AHI has an arbitrary threshold of 10 seconds for a respiratory event to be counted, even though shorter breathing events can yield significant oxygen desaturations.

“Thus, two individuals with the same AHI may have vastly different symptoms and health outcomes due to differences in their desaturations,” says Sharma.

Another potential shortfall of the AHI is that apneas, complete pauses in breathing, and hypopneas, when breathing becomes shallow, have the same weight in the AHI calculation.

Since AHI disregards the severity of dips in oxygen saturation, a patient could, for instance, desaturate into the 70s during a night of sleep, but still have “mild” sleep apnea because the total number of apneas per hour is low. Hypoxic burden could help fill this gap in identifying these patients, who might otherwise slip through the cracks.

“As more knowledge develops and more research comes out, I think we will be doing more and more with hypoxic burden for follow-up because we might be missing people who we are not treating appropriately or adequately if they are still getting hypoxic,” says Sharma.

What would be the tipping point that would drive hypoxic burden into the mainstream and help the metric gain acceptance by sleep physicians? Robyn Woidtke, MSN, RN, RPSGT, a clinical consultant for Panthera, says there would need to be policy statements by the professional organizations and acceptance by payors (public or private) to accept the new definition as a means for diagnosis and treatment. In medicine, she explains, there is a certain amount of inertia.

“It’s easy to continue with the status quo,” says Woidtke. “Sleep professionals are comfortable in using an established measure such as the AHI in patient discussions, so if the focus changes from AHI to other measures such as [hypoxic burden], we will need to rewrite the script.”

References

1. Azarbarzin A, Sands SA, Stone KL, et al. The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Eur Heart J. 2019 Apr 7;40(14):1149-57.
2. Parekh A. Hypoxic burden – definitions, pathophysiological concepts, methods of evaluation, and clinical relevance. Curr Opin Pulm Med. 2024;30(6):600-606.
3. Peker Y, Zinchuk A, Celik Y, et al. Hypoxic burden but not AHI predicts risk of cardiovascular events: A secondary analysis of the RICCADSA clinical trial. Am J Respir Crit Care Med. 2024;209:A4730.
4. Sharma S, Conflitti A, Reiter H. Assessment of sleep apnea-specific hypoxic burden (SASHB) with novel oral appliance Optima and oral positive expiratory pressure accessory ExVent. AADSM 2024. 2024 17 May.
5. Mosca EV, Grosse J, Remmers JE. Oral appliance therapy is highly efficacious at reducing sleep apnea-specific hypoxic burden, a metric predictive of cardiovascular morbidity and mortality. J Clin Sleep Med. 2025 Mar 24.

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