Endothelial dysfunction is assessed in patients with chronic venous insufficiency of lower limbs (grade C4 according to C - clinical manifestations, E - etiologic factors, A - anatomic distribution of disease, and P - underlying pathophysiologic findings (CEAP) classification) prior to and after endovenous surgical procedure, i.e. endovenous laser ablation of great saphenous vein, microphlebectomy of varicose branches. Two treatment groups (with and without additional pharmacotherapy) are compared.

Each patient will be examined 4 times:

Visit 1 (day -1)

• collecting and documenting patients' complaints and medical history
• local examination
• ultrasound angiography of the lower limbs veins
• assessment of clinical grade according to CEAP classification

Visit 2 (day 0)

• assessment of venous disease severity according to Venous Clinical Severity Score (VCSS)
• assessment of quality of life with Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ-20)
• assessment of clinical grade according to CEAP classification
• measurement of microcirculation in the operated limb by laser flowmetry using portable device (laser Doppler flowmetry (LDF) registration will be performed on leg anterior surface (lower third) for 10 minutes)
• assesment of blood laboratory parameters of endothelial dysfunction: homocysteine, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1), E-selectin, P-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular endothelial cell adhesion molecule-1 (sVCAM-1)
• flow cytometry analysis of circulating cells expressing surface markers (clusters of differentiation (CD)): CD 45-, CD 34+, CD 146+, CD 31+, CD 105+ and CD 309+
• surgical treatment is performed as endovenous laser ablation of GSV and microphlebectomy of varicose branches according to a standard protocol
• patients' randomization (method of random numbers) into 2 treatment groups of 20 subjects each with sulodexide treatment (250 LSU bid for 30 day) for the active treatment group and without any additional pharmacotherapy for the control group

Visit 3 (day 4 after intervention)

- ultrasound angiography of the operated limb (evaluation of the venous ablation and examination of endothermal heat-induced thrombosis (EHIT))

Visit 4 (day 32 after intervention)

• collecting and documenting patients' complaints
• local examination
• ultrasound angiography of the lower limbs veins
• assessment of clinical grade according to CEAP classification
• assessment of venous disease severity according to VCSS
• assessment of quality of life with CIVIQ-20
• measurement of microcirculation in the operated limb by laser flowmetry using portable device
• assesment of blood laboratory parameters of endothelial dysfunction: homocysteine, von Willebrand factor, PAI-1, E-selectin, P-selectin, sICAM-1, sVCAM-1
• flow cytometry analysis of circulating cells expressing surface markers: CD 45-, CD 34+, CD 146+, CD 31+, CD 105+ and CD 309+

Inclusion Criteria:

• Men and women aged 18-65 years inclusive.
• Diagnosis: varicose veins of lower limbs in the GSV territory.
• Maximum diameter of target vein (GSV) - 15 mm.
• Clinical grade C4 according to CEAP classification.
• Absence of chronic diseases or acute diseases requiring first-line treatment.

Exclusion/withdrawal Criteria:

• Conditions that limit patient's adherence to study procedures (dementia, neuropsychological disorders, substance and alcohol dependence, etc.).
• Participation in other clinical trials (or administration of investigational medicinal products) within 3 months prior to the study.
• Patient's withdrawal from the study.
• History of thrombosis of superficial and/or deep veins of lower limbs at enrollment into the study.
• Current anticoagulant and phlebotropic therapy.
• Comorbidities requiring first-line treatment.

6 months after completion of the study

upon request