Circulating 4-Hydroxynonenal Is Associated with Clinical Severity in ST-Segment Elevation Myocardial Infarction

Oxidative stress and ferroptosis are increasingly recognized as key contributors to the pathogenesis of ST-segment elevation myocardial infarction (STEMI), although the clinical relevance of circulating molecules linked to these processes remains insufficiently defined. The present study evaluated serum levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE), as well as glutathione peroxidase 4 (GPX4), in patients with STEMI and controls, and explored their relationship with clinical severity. Serum concentrations of 4-HNE and GPX4 were measured, and their associations with clinical risk scores and major outcomes were analyzed using correlation and regression methods. Compared with controls, patients with STEMI showed significantly higher 4-HNE concentrations (median, 1220.2 [IQR, 806–1453] vs. 38.7 [15.6–584]; p < 0.001), whereas GPX4 levels were significantly lower in STEMI patients (median, 8.85 [8–10.56] vs. controls 10.50 [9.31–12.11]; p = 0.003). Increased 4-HNE levels were positively associated with the TIMI score (ρ = 0.385, FDR-adjusted p = 0.026) and Killip–Kimball class (ρ = 0.329, p = 0.016; FDR-adjusted p = 0.041), suggesting a relationship with greater clinical severity. Although unadjusted analysis indicated an association between higher 4-HNE concentrations and cardiovascular mortality (OR, 1.0033; 95% CI, 1.0004–1.0083; p = 0.0176), this finding was not significant after multivariable adjustment. Overall, these findings indicate that STEMI is associated with increased lipid peroxidation and reduced GPX4 levels, supporting the involvement of ferroptosis-related pathways in acute myocardial infarction. Elevated 4-HNE levels were also associated with greater clinical severity.