Evaluation of Varicose Vein-derived Blood Biomarkers for Venous Surveillance

Intervention for patients with symptomatic varicose veins is largely driven by a combination of symptoms, the magnitude of venous reflux, clinical severity scoring algorithms, and unresponsiveness to medical therapy. We evaluated the wall of superficial veins from patients with symptomatic varicose veins, comparing this with healthy veins, for biological insight into progression of superficial vein disease. RNA was extracted from incompetent greater saphenous vein (GSV) at the time of phlebectomy and compared with residual healthy superficial veins following coronary artery bypass graft surgery. The venous transcriptome was interrogated by Nanostring. Panther and Gene Ontology identified biological pathways of interest, and, based on this data, plasma biomarkers form varicose vein patients or matched controls was evaluated by ELISA. The relationship between target blood biomarker concentration and venous reflux time was then assessed. Multiple genes were unregulated and down regulated (Fig 1) in pathways involving angiogenesis, collagen biosynthesis, and inflammation. COL10A1 and COL1A1 were unregulated in varicose vein by 12-fold and 5-fold, respectively, while interleukin-6 (IL-6) was downregulated by >30-fold. Blood (IL-6) was higher in the blood of varicose vein vs healthy vein patients (4.8 vs. 1.3 pg/mL; P = .0085) and distinguished varicose vein patients from healthy vein individuals by receiver operating characteristic curve analysis with area under the curve (AUC) = 70% (range, 57%-83%; P = .009). Blood collagen 1A1 (Col-1A1) was lower in the blood of patients with varicose veins vs healthy patients (66,355 vs 82,661 pg/mL; P = .04). Only blood (Col1A1) was related to reflux times with an inverse correlation (r = −0.51; P = .0098) (Fig 2). Blood (Col1A1) and possibly IL-6 may be blood biomarkers used in conjunction with venous reflux times as additional objective data that that may indicate adverse remodeling of the vein, and assist in decision-making for interventional therapy.Fig 2Blood biomarkers and relationship between saphenous vein reflux times in incompetent saphenous veins and blood biomarker concentration. A, Blood from 28 matched controls and 28 patients with varicose veins were evaluated by ELISA for interleukin-6 (IL-6) and for fragments of collagen-1 and collagen-10. Data were interrogated for normalcy and differences between groups was determined by Mann-Whitney U. The level of significance is shown above each graph. B, Blood from patients with varicose veins evaluated by ELISA for IL-6 and for fragments of collagen-I and collagen-X as a function of reflux time in an incompetent superficial vein of the lower extremity. Association was assessed by Pearson's Rho.