Normal endothelial peripheral arterial tonometry values in healthy children: A systematic review and meta-analysis.

INTRODUCTION: Endothelial dysfunction is an early, reversible marker of cardiovascular disease that can already be detected in childhood. EndoPAT (endothelial peripheral arterial tonometry) provides a noninvasive and operator-independent assessment of endothelial function, but pediatric reference values are not established. By pooling EndoPAT-derived data from existing studies in healthy children, this meta-analysis aims to derive normative values and to evaluate the influence of age, sex, and body mass index (BMI) on endothelial function. METHODS: PubMed, Web of Science, and EMBASE were searched up to April 2026 for studies reporting EndoPAT measurements in healthy children aged 5-18 years. Data on study characteristics, participant demographics, and vascular parameters were extracted. Pooled estimates were calculated using random-effects models and meta-regression explored effects of age, sex, and BMI. The study protocol was registered in the PROSPERO database (CRD42025643846). RESULTS: From 8573 records, 54 studies including 3555 healthy children (13.5 ± 2.5 years) were analyzed. The pooled mean reactive hyperemia index (RHI) was 1.73 (95% CI: 1.66-1.81), and meta-regressions showed that RHI increased with age and BMI, with no significant association observed with sex. CONCLUSION: This meta-analysis demonstrates that adult-derived RHI cutoffs for endothelial dysfunction are not applicable to children. Vascular function during childhood is influenced by age, pubertal stage, and BMI. Therefore, low RHI values in children likely reflect ongoing microvascular maturation rather than true endothelial dysfunction. These findings support the use of pediatric reference values for RHI and highlight the need for standardized pediatric EndoPAT protocols, as well as longitudinal studies to establish normal developmental trajectories and to identify early clinically relevant deviations.