Redox imbalance and metabolic stress in carotid atherosclerosis: Associations with symptomatology and plaque calcification

Abstract

Background and aims: Oxidative stress (OS) is a central driver of atherosclerosis, yet its role in carotid plaque vulnerability and neurological symptoms remains insufficiently defined. This study aimed to comprehensively characterize the redox and metabolic profiles of carotid plaques and evaluate their associations with plaque calcification and clinical symptomatology in patients undergoing carotid endarterectomy. Methods and results: Ninety-two patients were prospectively enrolled. Patients were classified as symptomatic or asymptomatic according to recent neurological events, and plaques were categorized as calcified or non-calcified based on preoperative angio-CT. Excised tissue was analyzed for total antioxidant capacity (FRAP, ABTS), enzymatic defenses (catalase, superoxide dismutase [SOD]), oxidative damage markers (8-hydroxy-2′-deoxy- guanosine [8-OHdG], malondialdehyde + 4-hydroxy-2-nonenal [MDA + HNE]), uric acid, and lactate. Non- calcified plaques exhibited reduced antioxidant activity (ABTS: 2635.08 vs. 2803.28 μM, p = 0.007), lower SOD activity (1.11 vs. 1.49 U/mL, p = 0.049), and higher lactate levels (11.45 vs. 8.57 mg/dL, p = 0.001), indicating metabolic instability. Symptomatic patients showed higher uric acid (p = 0.001), reduced SOD (p = 0.009), and increased lipid peroxidation, while FRAP and ABTS did not differ significantly. The two analytical axes did not fully overlap, as 75 % of non-calcified and 60 % of calcified plaques derived from symptomatic patients (p = 0.235). Conclusion: Carotid plaques associated with symptoms and lacking calcification displayed redox imbalance and metabolic dysfunction, suggesting a more biologically active and rupture-prone phenotype. Importantly, these findings support the integration of tissue oxidative biomarkers with clinical and imaging data to refine stroke risk stratification, guide secondary prevention, and improve postoperative surveillance strategies.