Glycation burden and glycemic variability: Key drivers of chronic venous insufficiency severity and adverse outcomes

Aim: Advanced glycation end-products (AGEs) have been implicated in vascular pathology, but their role in chronic venous insufficiency (CVI) remains underexplored. This study investigated the association between glycated hemoglobin (HbA1c), a surrogate marker of glycation burden, and CVI severity and outcomes.

Material and Methods: This single-center retrospective cohort study included 612 patients with CVI. Patients were stratified by glycation burden: high (high glycation burden (HGB); HbA1c ≥6.5%, n=247) and low (low glycation burden (LGB); HbA1c <6.5%, n=365). CVI severity was assessed using Clinical, Etiological, Anatomical, and Pathophysiological (CEAP) classification and Venous Clinical Severity Score (VCSS). Major adverse venous events (MAVEs) were tracked over 36 months.

Results: HGB patients showed higher rates of advanced CVI (CEAP C4-C6: 41.7% vs. 26.0%, p<0.001) and higher VCSS scores (median 9 vs. 7, p<0.001). HbA1c variability (SD) strongly correlated with VCSS (ρ=0.38, p<0.001). In multivariable analysis, HbA1c ≥6.5% (OR 1.52, 95% CI 1.02-2.30), HbA1c SD (OR 2.10, 95% CI 1.45-3.06), and HOMA-IR (OR 1.19, 95% CI 1.07-1.33) independently predicted severe CVI. MAVEs were more frequent in HGB patients (14.2% vs. 8.5%, p=0.021).

Conclusion: Glycation burden and glycemic variability are independently associated with CVI severity and adverse outcomes. These findings suggest that metabolic dysfunction contributes to venous pathology and may represent potential therapeutic targets.