Autism Spectrum Disorder and Cardiovascular Risk: The Role of Frontal QRS–T Angle and Systemic Immune-Inflammation Index

Objective Autism spectrum disorder (ASD) has been linked to autonomic dysregulation and low-grade systemic inflammation, but their expression on routine electrocardiography (ECG) in pediatric samples remains unclear. We examined whether inflammatory indices relate to ECG markers, particularly the frontal QRS–T angle (fQRS–T), in youths with ASD.Methods In this case—control study, children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition— confirmed ASD and age- and sex-matched healthy controls (HC) were enrolled. Sociodemographic data, complete blood counts, biochemistry/hormones, and standard 12-lead ECGs were obtained. Inflammatory composites included the systemic immune-inflammation index (SII), systemic inflammatory response index, and pan-immune-inflammation value. fQRS–T was derived from the automated ECG report as the absolute difference between frontal QRS and T axes (0°–180°) and verified by clinician review.Results Eighty-four ASD participants and 82 HC were analyzed, with no age or sex differences. Compared with HC, ASD showed higher heart rate (97.56±21.20 bpm vs. 84.63±17.02 bpm; p=0.004) and a wider fQRS–T (median 23.5° [IQR 5.75–43.25] vs. 18° [IQR 3.5–31.5]; p=0.005). SII was modestly higher in ASD (539.66 vs. 453.14; p=0.030). Autism Behavior Checklist scores correlated with SII (r=0.387; p=0.041) and fQRS–T (r=0.566; p=0.002), but not with heart rate (r=0.117; p=0.546). SII also correlated with fQRS–T (r=0.424; p=0.010).Conclusion ASD was associated with increased fQRS–T and SII despite largely normal conventional ECG intervals, and behavioral severity tracked with both inflammatory tone and repolarization heterogeneity, suggesting a possible association between inflammatory, autonomic, and electrophysiological processes.