OBJECTIVE
To evaluate the effects of sulodexide (Vessel Due F), endovenous laser ablation (EVLA), and their combination on the dynamics of endothelial dysfunction and venous-specific inflammatory biomarkers in patients with chronic venous disease (CVD) of the lower extremities classified as CEAP C4—C6.
MATERIALS AND METHODS
Ninety-three patients with CVD (CEAP classes C4—C6) were enrolled in the study. Patients were allocated into four groups: (1) compression therapy; (2) EVLA; (3) sulodexide (Vessel Due F) 250 LSU twice daily for 2 months; and (4) EVLA followed by sulodexide at the same dosage. Serum levels of E-selectin, MCP-1, VEGF, MMP-2, and MMP-9 were measured using quantitative enzyme-linked immunosorbent assay at baseline (V0), 2 months (V2), and 12 months (V3).
RESULTS
In the compression group, a moderate reduction in E-selectin was observed at 2 months (60.7±2.8 → 56.6±2.5; p<0.01), with no significant difference at 12 months (60.5±2.7; p=0.84). MCP-1, MMP-2, VEGF, and MMP-9 showed no statistically significant changes (p>0.05). In the EVLA group, a marked early decrease in E-selectin (66.2±3.1 → 40.8±2.9; p<0.001) and MCP-1 (231.9±9.8 → 146.3±8.4; p<0.001) was observed, with partial return toward baseline values at 12 months. No significant changes were detected for MMP-2, VEGF, or MMP-9 (p>0.05). In the sulodexide group, MCP-1 (205.4±8.7 → 134.6±7.2; p<0.001) and MMP-2 (421.7±14.8 → 249.0±13.1; p<0.001) significantly decreased at 2 months, with values approaching baseline at 12 months (MCP-1 205.8±8.1; p=0.96; MMP-2 407.2±15.0; p=0.09). MMP-9 significantly decreased both at 2 months (69.2±3.4 → 58.9±3.1; p<0.001) and 12 months (63.8±3.2; p<0.001). E-selectin and VEGF did not change significantly (p>0.05). In the EVLA+sulodexide group, E-selectin significantly decreased at 2 months (67.4±3.5 → 55.8±3.0; p<0.001) and remained reduced at 12 months (55.9±3.1; p<0.001). MCP-1 decreased at 2 months (284.3±11.2 → 203.4±9.6; p<0.001) and remained significantly lower than baseline at 12 months (235.1±10.4; p=0.03). MMP-2 significantly decreased at V2 (529.3±18.6 → 263.8±14.9; p<0.001) with a trend toward persistence at V3 (489.3±17.4; p=0.07). MMP-9 significantly decreased at both time points (74.8±3.9 → 64.8±3.4; p<0.001; and 69.8±3.6; p<0.001). VEGF did not show significant changes at any follow-up time point (p>0.05).
CONCLUSION
Vessel Due F was associated with significant reductions in MCP-1 and matrix metalloproteinases, with the most sustained decreases in MCP-1, E-selectin, MMP-2, and MMP-9 observed in the combined treatment group (EVLA+sulodexide). In patients with CVD classified as CEAP C4—C6, compression therapy demonstrated minimal impact on systemic inflammatory and remodeling biomarkers. EVLA provided a pronounced early reduction in endothelial activation (E-selectin) and inflammatory activity (MCP-1), although partial attenuation of this effect was observed at long-term follow-up. Serum VEGF levels did not change significantly in this cohort.
