How can clinicians identify patients with obstructive sleep apnea (OSA) who are most likely to experience cardiovascular (CV) benefits from positive airway pressure therapy? Two physiologic biomarkers derived from sleep recordings may help identify patients at high CV risk who are more likely to benefit from treatment adherence.

During the European Respiratory Society (ERS) 2026 International Congress, Frédéric Gagnadoux, MD, professor of pulmonology and head of the Department of Pulmonology and Allergy at Angers University Hospital in Angers, France, presented findings on the use of these biomarkers to stratify CV risk in patients with OSA.

The findings were published in the European Respiratory Journal.

OSA is a heterogeneous condition whose severity cannot be adequately characterized using the apnea-hypopnea index (AHI) alone.

AHI measures the frequency of apneas and hypopneas per hour of sleep but may not fully capture the physiologic disturbances associated with CV risk.

Two physiologic biomarkers may help characterize OSA more precisely, identify patients at increased CV risk, and determine who is most likely to benefit from continuous positive airway pressure (CPAP) therapy.

The first biomarker, hypoxic burden (HB), quantifies the cumulative exposure to intermittent hypoxemia caused by respiratory events. It is calculated as the area under the oxygen desaturation curve relative to the total sleep time.

The specific parameter used was sleep apnea-specific HB (SASHB). Unlike AHI, HB accounts for both the depth and duration of oxygen desaturation. “It thus provides a more physiological measure of exposure to intermittent hypoxemia,” said Gagnadoux.

HB may improve CV risk stratification and help identify patients who are likely to benefit from CPAP.

A post hoc analysis of the ISAACC trial assessed its potential to refine CPAP treatment allocation.

The second biomarker, heart rate (HR) response, measures the increase in HR following an obstructive respiratory event and is expressed in beats/min. It serves as an indirect marker of autonomic activity, particularly sympathetic activation, during and after respiratory events. A greater increase in HR (ΔHR) is associated with a higher CV risk in patients with OSA and may help identify those more likely to benefit from CPAP.

This response can also be estimated automatically from pulse oximetry, yielding ΔHRₒₓᵢ without requiring manual scoring of respiratory events. This measure has also been shown to predict the CV benefits associated with CPAP adherence.

Combining Biomarkers to Stratify CV Risk

In patients with OSA and established CV disease, combining SASHB and ΔHR may help identify a phenotype associated with high CV risk. This finding was obtained from an individual patient-level post hoc analysis of data from the randomized RICCADSA, ISAACC, and SAVE trials.

The high-risk OSA phenotype was defined by the presence of at least one of two criteria: an SASHB > 87.1% min/h or an HR response > 9.4 beats/min. Either substantial intermittent hypoxemia or a pronounced HR response to obstructive respiratory events was sufficient to classify a patient as high risk.

The association between CPAP therapy and major adverse CV events (MACE), including CV death, myocardial infarction, and stroke, differed according to the physiologic risk profile. The hazard ratio (HR) was 0.83 among patients with high-risk OSA and 1.22 among those classified as low risk (P for interaction = .024).

Gagnadoux summarized the findings: “The integration of SASHB and ΔHR makes it possible to identify a phenotype of patients with OSA who are at high CV risk, characterized by significant exposure to intermittent hypoxemia and/or marked CV activation.”

Which Patients Benefit From Good CPAP Adherence?

The objective of the study was to examine whether SASHB and ΔHR could identify patients seen in sleep clinics who were more likely to benefit from CPAP adherence in terms of mortality and CV events. The analysis used data from the Pays de la Loire Sleep Cohort linked to the French National Health Data System.

The primary endpoint was a composite of MACE, defined as hospitalization for coronary heart disease, stroke, heart failure exacerbation, or death from any cause.

The cohort included 3370 patients with moderate-to-severe OSA, defined as an AHI ≥ 15 events per hour. The median follow-up was 9 years, and the median age was 57 years. Men accounted for 69.3% of the participants.

The median AHI was 37 events per hour, and the median Epworth Sleepiness Scale score was 10. Hypertension was present in 42.3% of the patients, and 17.5% had a history of CV disease.

Using the study thresholds of SASHB > 40.6% min/h and HR response > 21.7 beats/min, 71.7% of patients were classified as high risk and 28.3% as low risk. Overall, 53% adhered to CPAP therapy, defined as use for ≥ 4 hours per night.

CPAP adherence was associated with a lower risk for MACE than nonadherence (adjusted HR, 0.53; 95% CI, 0.46-0.62; P < .001).

This association was stronger among patients classified as high risk than among those classified as low risk (interaction HR, 0.61; 95% CI, 0.43-0.87; P for interaction = .006).

What Are the Clinical Implications?

In conclusion, adherence to CPAP was associated with a reduction in the incidence of MACE only among patients with a high-risk phenotype defined by the SASHB-ΔHR biomarkers.

“The combination of SASHB and ΔHR, derived from sleep recordings, makes it possible to identify, among patients seen in sleep clinics, a phenotype associated with greater CV benefit from long-term CPAP adherence.

Biomarkers reflecting hypoxic burden and autonomic response could help personalize CV risk stratification and identify patients likely to benefit from CPAP, particularly those with minimally symptomatic OSA,” said Gagnadoux.

Gagnadoux reported having relationships with Asten Santé, Air Liquide Santé, Bioprojet, BMC, CIDELEC, Inspire Medical Systems, Pharmanovia, Philips Respironics, Resmed, and Sefam.

This story was translated from Medscape’s French edition.