Oxidative Stress Biomarkers (Malondialdehyde, Superoxide Dismutase, and Catalase) as Predictors of Cardiovascular Disease Risk: A Review

Abstract

Oxidative stress drives cardiovascular disease pathogenesis through endothelial dysfunction, lipid peroxidation, and vascular inflammation. Malondialdehyde, a stable lipid peroxidation end-product, serves as a widely used marker of oxidative damage, while superoxide dismutase and catalase represent key enzymatic antioxidants that neutralize reactive oxygen species-mediated injury. Evidence consistently shows that elevated MDA levels correlate with cardiovascular disease severity and adverse outcomes, whereas reduced SOD and catalase activities reflect compromised antioxidant defense in patients with coronary artery disease, hypertension, and heart failure. MDA demonstrates independent predictive value beyond conventional risk models — principally the Framingham Risk Score — with AUC values reaching 0.94 for severe coronary artery disease and hazard ratios of 2.0 – 3.3 for cardiovascular mortality. Composite indices such as the MDA/SOD ratio and Oxidative Stress Index consistently outperform individual markers and provide incremental reclassification benefit, particularly among intermediate-risk individuals. However, clinical translation remains limited by the predominant use of the non-specific TBARS assay over the more accurate HPLC method, absence of standardized reference ranges, insufficient ethnic diversity in the evidence base, and lack of guideline incorporation. Assay standardization, large-scale prospective validation across diverse populations, and development of point-of-care platforms represent the critical priorities for advancing these biomarkers toward routine cardiovascular risk assessment.