Differential Associations of Oxidative Biomarkers with Symptomatic and Systolic Severity in Heart Failure

Background and Objectives: Oxidative stress is recognized as an important contributor to heart failure (HF) pathophysiology, but the relationships of individual oxidative and antioxidant biomarkers with symptomatic severity and systolic dysfunction remain insufficiently defined. This study examined circulating oxidative and nitrosative stress markers across New York Heart Association (NYHA) classes and left ventricular ejection fraction (LVEF) categories in HF and their associations with HF severity. Materials and Methods: In this case-control study, 85 patients with HF and 33 healthy controls were included. Malondialdehyde (MDA), nitrates and nitrites (NOx), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), sulfhydryl (SH) groups, and NT-proBNP were measured. Group differences were analyzed using the Kruskal-Wallis test with post hoc comparisons. Adjusted ordinal logistic regression models examined associations with NYHA class and LVEF category, and receiver operating characteristic (ROC) analysis evaluated discriminatory performance. Results: Compared with controls, all biomarkers differed significantly across NYHA classes and LVEF categories (all p < 0.001). In separate adjusted models, higher NOx, MDA, and NT-proBNP were associated with worse NYHA class and more impaired LVEF, whereas higher antioxidant marker levels were associated with lower odds of severe HF. In combined models, NOx remained independently associated with worse NYHA class (OR 1.07, 95% CI 1.04-1.11; p < 0.001), while MDA remained independently associated with more impaired LVEF (OR 1.02, 95% CI 1.00-1.03; p = 0.022). NT-proBNP showed the best discrimination for NYHA III/IV versus I/II (AUC 0.966), while among oxidative biomarkers NOx performed best for symptomatic severity (AUC 0.782) and MDA for LVEF ≤ 40% (AUC 0.751). Conclusions: HF is characterized by increased oxidative and nitrosative stress together with reduced antioxidant defense. NOx appears more closely related to symptomatic severity, whereas MDA appears more closely related to systolic dysfunction. However, NT-proBNP remained the strongest overall discriminator. NOx and MDA may provide complementary mechanistic information on redox imbalance across HF severity categories.