Association between plasma homocysteine levels and P-wave dispersion in pediatric patients with hyperhomocysteinemia

Hyperhomocysteinemia has been recognized as a cardiovascular risk factor associated with endothelial dysfunction, oxidative stress, and vascular inflammation. Experimental and clinical studies suggest that elevated homocysteine levels may also influence myocardial electrophysiology and contribute to arrhythmogenesis. However, data regarding the relationship between homocysteine levels and electrocardiographic markers of atrial conduction in pediatric populations remain limited. This study aimed to evaluate the association between plasma homocysteine levels and electrocardiographic parameters, particularly P-wave dispersion, in children. This multicenter retrospective case-control study included pediatric patients evaluated in four tertiary pediatric metabolism centers between January 2023 and December 2025. A total of 47 patients with hyperhomocysteinemia (plasma total homocysteine ≥ 15 µmol/L) and 43 age- and sex-matched controls with normal homocysteine levels were included. Controls were selected from the screened population among children with available homocysteine measurements, electrocardiographic and echocardiographic evaluations, and no confirmed inherited metabolic disease or cardiac disorder. Clinical, biochemical, and electrocardiographic parameters, including maximum P-wave duration and P-wave dispersion, were retrospectively analyzed. A total of 90 participants were included, comprising 47 children with hyperhomocysteinemia and 43 healthy controls. P-wave dispersion and maximum P-wave duration were significantly higher in the hyperhomocysteinemia group compared with controls (48.96 [19.48-100.0] vs. 38.57 [10.57-71.19] ms, p < 0.001). Plasma homocysteine levels showed a moderate positive correlation with P-wave dispersion (ρ = 0.441, p < 0.001). These differences were more pronounced in children with higher homocysteine levels and in younger age groups (< 2 years and 2-14 years). In contrast, PR interval (p = 0.790) and QTc interval (p = 0.183) did not differ significantly between groups. Vitamin B12 levels were significantly lower in the hyperhomocysteinemia group (p = 0.013), while folate levels were comparable (p = 0.974). Although sodium, potassium, and magnesium levels differed significantly between groups, all values remained within normal physiological ranges.

Children with hyperhomocysteinemia showed increased P-wave dispersion compared with controls. These findings suggest an association between elevated homocysteine levels and altered atrial conduction parameters in children. Further prospective studies are needed to determine the clinical significance of these findings.

• Hyperhomocysteinemia is associated with cardiovascular risk and endothelial dysfunction. • Elevated homocysteine levels have been linked to cardiac electrophysiological alterations in adult populations.

• Elevated homocysteine levels are associated with increased P-wave dispersion in children, with more pronounced effects observed in younger age groups. • These findings support an association between hyperhomocysteinemia and altered atrial conduction parameters in children.