Diagnosis, treatment and evaluation of chronic venous disease

BACKGROUND AND AIMS: Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) in the Western hemisphere. Recent research shows that the disease encompasses the global population and with similar prevalence. The most severe form of CVD is venous ulceration with a prevalence of about 1% that does not only cause great suffering but is also costly for the society. The aims of this thesis were to investigate ways in improving prioritization, diagnosis, and surgical treatment of patients with VV that have the potential risk of developing VU.

METHODS: Cross-sectional (Studies I, III and IV) and follow-up (Study II) studies were carried out. Study I investigated the inter-observer reproducibility of the clinical class of CEAP and whether there was a medical indication for treatment. Seventy-eight patients (106 limbs) with varying degree of CVD were included. Three independent physicians assessed the patients. In study II, we assessed the ulcer recurrence rate in patients with healed or active venous ulcer (VU) that were treated with endovenous laser ablation (EVLA) for superficial venous incompetence. One hundred and seventy patients (195 limbs) of consecutively treated patients were followed-up. Study III investigated the association between the biomarker E-XDP in plasma and the presence or severity of CVD. Samples of blood were drawn from a total of 142 patients with CVD and were matched to VU patients. In Study IV, 112 patients with CVD were included. The VEINES-QOL/Sym questionnaire was translated into Swedish and evaluated with regards to its psychometric properties.

RESULTS: In Study I, total agreement between the three observers for clinical class was obtained in 61% of all cases (κ 0.55-0.68 (95% CI)) and for medical indication 60% of all cases (κ 0.35-0.57 (95% CI)). Study II showed that all patients had healed their original ulcer and 84% of the limbs had no recurrence after 3.5 years. In Study III, E-XDP levels were elevated in patients with CVD compared with controls (p< 0.05) and increased with increasing disease severity (p = 0.02). Multiple linear regression confirmed that E-XDP was independently associated with CVI (p < 0.05) after adjustment for age and gender. Study IV showed excellent internal consistency for both VEINES-QOL (Cronbach’s alpha (α) = 0.93) and VEINES-Sym (α = 0.89). Both the VEINES-QOL and VEINES-Sym correlated well to all the RAND-36 domains, demonstrating good construct validity. Exploratory factor analysis confirmed both subscales of the VEINES-QOL/Sym.

CONCLUSIONs: Diagnosis using the clinical class of CEAP has moderate reproducibility when deciding medical indication for treatment and EVLA in VU patients achieves good healing with low recurrence rates and low rates of complications. Further, the novel biomarker E-XDP appears to have a positive association with increasing disease severity. The Swedish version of the VEINES-QOL/Sym is valid in assessing health related quality of life in CVD, both clinically and in research.

List of scientific papers

I. Inter-observer variability in the assessment of the clinical severity of superficial venous insufficiency. Sinabulya H, Holmberg A, Blomgren L. Phlebology, 2015, vol. 30 no. 1, 61-65
https://doi.org/10.1177/0268355513515474

II. Mid-term outcomes of endovenous laser ablation in patients with active and healed venous ulcers : a follow-up study. Sinabulya H, Östmyren R, Blomgren L. Eur J Vasc Endovasc Surg, 2017.
https://doi.org/10.1016/j.ejvs.2017.02.028

III. Cross linked fibrin degradation products in plasma are elevated in chronic venous disease. Sinabulya H, Silveira A, Blomgren L, Roy J. [Manuscript]

IV. Cultural adaptation and validation of the Swedish VEINES-QOL/Sym in patients with venous insufficiency. Sinabulya H, Bergström G, Hagberg J, Johansson G, Blomgren L. [Submitted]