A new multicenter clinical study highlighted the potential of hypoxic burden (HB) as a biomarker for cardiovascular (CV) risk in children with OSA, offering clinicians a more nuanced tool for risk stratification and management.1
The secondary analysis, conducted within the Kids Trial cohort at two university hospitals in Spain, was reported by lead investigator Olga Mediano, PhD, from the Hospital Universitario de Guadalajara, Guadalajara, Spain, and colleagues. The team evaluated 190 children (with a median age of 6 years) with suspected OSA. The study aimed to determine whether HB correlated with nocturnal BP patterns and the prevalence of the nondipping pattern (NDP), both established markers of CV risk.
Researchers found that elevated HB was associated with adverse BP patterns. Children with higher HB exhibited greater nocturnal diastolic BP, a reduced nocturnal decrease in mean BP, and a higher prevalence of the NDP. Specifically, those in the highest HB quartile had a more than twofold increased risk of the NDP compared with those in the lowest quartile (OR, 2.41; 95% CI, 1.00-5.79; P = .05).
The study also found that HB values were higher during REM sleep and in the supine position, which mirrors patterns seen in adults. In children, however, the most pronounced BP alterations were observed in nocturnal diastolic BP, suggesting developmental differences in vascular regulation.
“While the apnea-hypopnea index (AHI) has long been the standard for determining OSA severity, it does not fully capture the physiological consequences of OSA. HB, by integrating the frequency, duration, and depth of oxygen desaturation events, provides a more comprehensive assessment of hypoxemia and its cardiovascular implications,” Dr. Mediano said.
The findings suggest that HB could serve as a practical and automated biomarker for CV risk in pediatric OSA, potentially guiding earlier and more targeted interventions. Unlike AHI, HB can be derived directly from pulse oximetry signals, streamlining the diagnostic process and reducing reliance on labor-intensive polysomnography scoring.
“The automation and simplicity of HB calculation have profound implications for accessibility and patient care,” Dr. Mediano said. “It can easily be integrated into existing diagnostic pathways, including those in primary care or resource-limited settings. This allows us to reach a much larger patient population, significantly helping to combat the current underdiagnosis of OSA and its associated CV risk. Furthermore, the use of simple home oximetry is more comfortable for the child, avoiding the complexities and costs of a full sleep lab stay.”
As AHI remains the primary metric for diagnosing and quantifying the frequency of respiratory events, the investigators do not foresee HB entirely replacing AHI just yet. But they do strongly recommend that HB be adopted as a mandatory complementary measure for CV risk stratification.
“HB is a superior marker because it captures the cumulative physiological impact of intermittent hypoxia—the ‘dose’ of oxygen deprivation—which appears to be the most relevant factor driving vascular dysfunction. This is further supported by adult data, which showed that HB is independently and robustly associated with all-cause and cardiovascular mortality,” Dr. Mediano said.2
Early identification of children at risk for the NDP and associated CV complications is critical. The study underscores that even in the absence of overt hypertension, subtle BP pattern disturbances linked to elevated HB may predispose children to future CV disease. This is particularly relevant as childhood OSA is increasingly recognized as a contributor to long-term CV morbidity.3
“Our research team is currently analyzing if adenotonsillectomy successfully reduces HB and leads to the reversal of the NDP and normalization of BP parameters, as well as evaluating cardiovascular and inflammatory proteomic profiles—therefore, assessing long-term CV outcomes,” Dr. Mediano said.
Further validation studies will be needed to confirm the predictive value of HB for long-term morbidity such as hypertension and metabolic syndrome as children enter adolescence and young adulthood.
References
1. Mediano O, López-Monzoni S, Castillo-García M, et al. Cardiovascular risk through hypoxic burden in children with sleep apnea: a secondary analysis of a nonrandomized clinical trial. JAMA Netw Open. 2025;8:e2538744. doi:10.1001/jamanetworkopen.2025.38744
2. 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;40(14):1149-1157. doi:10.1093/eurheartj/ehy624. Erratum in: Eur Heart J. 2019;40(14):1157. doi:10.1093/eurheartj/ehz028
3. Castillo-García M, Solano-Pérez E, Coso C, et al. Impact of obstructive sleep apnea in cardiovascular risk in the pediatric population: A systematic review. Sleep Med Rev. 2023;71:101818. doi:10.1016/j.smrv.2023.101818
