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Clinical Trial
. 2025 Oct 1;8(10):e2538744.
doi: 10.1001/jamanetworkopen.2025.38744.

Cardiovascular Risk Through Hypoxic Burden in Children With Sleep Apnea: A Secondary Analysis of a Nonrandomized Clinical Trial

Olga Mediano  1   2   3   4 , Sonia López-Monzoni  1   3   4 , María Castillo-García  1   2   3   4 , Sofía Romero-Peralta  1   2   3   4 , María Esther Viejo-Ayuso  1   2   3 , Laura Silgado-Martínez  1   2   3 , Leticia Álvarez-Balado  1   2   3   4 , Carles Forné  5   6 , Pilar Resano-Barrio  1   2   3   4 , Francisco García-Rio  2   7 , Irene Cano-Pumarega  2   8 , Manuel Sánchez-de-la-Torre  2   3   9 , Alfonso Ortigado  4   10 , Laura Fidalgo  10 , Ángel Rodríguez  11 , Ainhoa Álvarez  12   13 , Jorge Ullate Mora  13 , Belén García-Mediano  1 , Ali Azarbarzin  14 , Esther Solano-Pérez  1   2   3
Affiliations
Clinical Trial

Cardiovascular Risk Through Hypoxic Burden in Children With Sleep Apnea: A Secondary Analysis of a Nonrandomized Clinical Trial

Olga Mediano et al. JAMA Netw Open. .

Abstract

Importance: Emerging biomarkers, such as hypoxic burden (HB), have demonstrated utility in estimation of cardiovascular (CV) risk in adults with obstructive sleep apnea (OSA). Its applicability in pediatric OSA remains unexplored.

Objective: To explore whether HB is associated with disturbances in blood pressure (BP) patterns in pediatric OSA.

Design, setting, and participants: Children with suspected OSA were included in this secondary analysis performed within the framework of the Kids Trial, a prospective, multicenter nonrandomized clinical trial, with data accrued between January 30, 2018, and August 28, 2023, at 2 university hospitals in Spain. A total of 286 children with suspected OSA were assessed for eligibility. Ninety-six children for whom HB was unavailable or with BP data that did not fulfill quality criteria were excluded.

Main outcomes and measures: Children underwent polysomnography and 24-hour ambulatory BP monitoring (ABPM). HB was quantified as the area under the desaturation curve of each respiratory event, relative to the pre-event baseline oxygen saturation. BP variables were obtained from ABPM.

Results: A total of 190 children were included in the analysis. Median age was 6 (IQR, 5-8) years, and 108 participants (56.8%) were male. Median apnea hypopnea index was 6.0 (IQR, 3.1-10.3) events per hour with a median HB of 9.6 (IQR, 3.8-22.5) %min/h. A comparison of the HB quartiles revealed that higher HB levels were associated with greater nocturnal diastolic BP (quartile 1: 56.0 [IQR, 52.0-60.0] mm Hg; quartile 2: 57.0 [IQR, 54.0-61.0] mm Hg; quartile 3: 59.0 [IQR, 53.0-61.0] mm Hg; and quartile 4: 58.0 [IQR, 55.0-61.0] mm Hg; P = .03), a reduced nocturnal decrease in mean BP (quartile 1: 13.5 [IQR, 8.0-18.2] mm Hg; quartile 2: 10.8 [IQR, 8.3-15.1] mm Hg; quartile 3: 11.4 [IQR, 8.7-15.2] mm Hg; and quartile 4: 8.9 [IQR, 6.6-13.5] mm Hg; P = .01), and an increased prevalence of a nondipping pattern (NDP) (quartile 1: 15 of 47 [31.9%]; quartile 2: 21 of 47 [44.7%]; quartile 3: 19 of 46 [41.3%]; and quartile 4: 26 of 47 [55.3%]; P = .04). Multivariable analysis showed an increased risk of NDP in the higher quartile of HB (odds ratio, 2.41; 95% CI, 1.00-5.79; P = .05).

Conclusions and relevance: In this secondary analysis of a nonrandomized clinical trial, elevated HB values were associated with an NDP and reduced nocturnal decrease in BP in children with OSA, both of which are established markers of CV risk. These results suggest the potential utility of HB as a biomarker for CV risk stratification and clinical management in the pediatric population with OSA.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mediano reported consulting for Eli Lilly and Company and ResMed Inc. Dr Azarbarzin reported receiving personal fees from Amgen Inc, Inspire Pharmaceuticals Inc, Eli Lilly and Company, Respicardia, Apnimed, and Incannex Healthcare Inc outside the submitted work and having a patent pending for a wearable device for endophenotyping obstructive sleep apnea. No other conflicts were disclosed.

Figures

Figure 1.
Figure 1.. Trial Flow Diagram
aSome participants were excluded for both reasons.
Figure 2.
Figure 2.. Measures of Hypoxic Burden (HB) for Different Sleep Stages and Positions as a Function of Obstructive Sleep Apnea (OSA) Severity in Pediatric Patients
Spearman rank correlation test was used. AHI indicates apnea-hypopnea index (calculated as the number of respiratory events per hour); REM, rapid eye movement.
Figure 3.
Figure 3.. Forest Plot Showing the Result of the Multivariable Logistic Regression Analysis for Nondipping Pattern According to Hypoxic Burden (HB) Levels
Odds ratios are adjusted for sex, age, and body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared).
See this image and copyright information in PMC

References

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