E-selectin and sICAM-1, biomarkers of endothelial function, predict recurrence of venous thromboembolism. Issue 157 (September 2017)

• Record Type: Journal Article
• Authors: Dzikowska-Diduch, Olga; Domienik-Karłowicz, Justyna; Górska, Elżbieta; Demkow, Urszula; Pruszczyk, Piotr; Kostrubiec, Maciej
• Is Part Of: Thrombosis research. Issue 157(2017)
• Page Start: 173
• Page End: 180
• Publication Date: 2017-09
• Subjects: AUC area under the curve -- ADMA asymmetric dimethylarginine -- APE acute pulmonary embolism -- CTEPH chronic thromboembolic pulmonary hypertension -- CD62E cluster of differentiation 62 E, E-selectin -- CRP C-reactive protein -- DVT deep vein thrombosis -- ED endothelial dysfunction -- ELISA enzyme-linked immunosorbent assay -- FMD flow-mediated dilation -- NMD nitroglycerin mediated dilation -- NPV negative predictive value -- NT-proBNP N-terminal fragment of pro-brain natriuretic peptide -- NTG nitroglycerin -- PPV positive predictive value -- ROC receiver operating characteristic -- RV right ventricle -- sICAM-1 soluble intercellular adhesion molecule 1 -- sVCAM-1 soluble vascular cell adhesion molecule 1 -- TAPSE tricuspid annular peak systolic excursion -- TRPG tricuspid regurgitation peak gradient -- VTE venous thromboembolism; Venous thromboembolism -- Endothelium function -- Biomarker -- Recurrence -- Embolism; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2017.07.027
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Background: Risk factors for atherosclerosis and venous thromboembolism (VTE) overlap and are mostly associated with endothelial dysfunction (ED). We hypothesized that ED is present in patients after the first episode of acute pulmonary embolism (APE) and predicts the risk of VTE recurrence. Design and Methods: Patients, at least 6 months after the first episode of symptomatic, confirmed APE were included in this case-control study. The exclusion criteria were risk factors for cardiovascular diseases and other conditions associated with endothelial dysfunction. Eighty two patients (aged 38 ± 11 years; 44 M; 38 F) were enrolled in the study, 39 after provoked APE, 43 after unprovoked APE, and 30 controls (C) (aged 38 ± 12 years; 15 M, 15 F). In order to evaluate the endothelial function in patients with a history of APE flow-mediated dilation (FMD) of the brachial artery and biomarkers of endothelial dysfunction (sVCAM-1, sICAM-1, ADMA, E-selectin) were measured. Subsequently all patients were followed up in an outpatient clinic for VTE recurrence. Results: FMD was more often impaired in APE patients than in controls (5.3% (0.8–20.3) vs. 13.8% (4.1–24.3); p < 0.0001). Biomarker levels differed between APE and C groups: sVCAM-1 (631 ng/ml (105–2382) vs. 495 ng/ml (348–934); p = 0.04) and sICAM-1 (679 ng/ml (279–1006) vs. 600 ng/ml (394–766); p = 0.002). There were 19 recurrences of VTE during the at least 12-month follow-up (15 with history of unprovoked-APE and 4 after provoked-APE). E-selectin ≥ 39 ng/ml and sICAM-1 ≤ 655 ng/ml indicated the group without recurrence of VTE. In a group of 43 unprovoked APE patients both E-selectin < 39 ng/ml and sICAM-1 > 655 ng/ml were found in 17 subjects. Eleven of them (65%) were diagnosed with recurrent VTE. Conclusions: Endothelial function is significantly impaired in patients after an episode of APE as indicated by FMD assessment and biomarker levels. Low concentrations of E-selectin and high levels of sICAM-1 are associated with a high risk of recurrent thromboembolism. Graphical abstract: The E-selectin and sICAM-1 blood concentrations in prediction of VTE recurrence. Highlights: Endothelial dysfunction (ED) may be associated with venous thromboembolism (VTE). We evaluated endothelial function in patients after acute pulmonary embolism (APE). Patients after APE have ED as indicated by flow-mediated dilation (FMD). The levels of sICAM and sVCAM, biomarkers of ED were higher in APE patients. Low level of E-selectin and high level of sICAM is associated with VTE recurrence.