E-selectin and vascular cell adhesion molecule-1 as biomarkers of 3-month outcome in cerebrovascular diseases

Sébastien Richard, Linnéa Lagerstedt, Pierre R. Burkhard, Marc Debouverie, Natacha Turck, Jean-Charles Sanchez

Inflammation is known to worsen cerebral damage at the acute phase of stroke. In this setting, cell adhesion molecules (CAMs) play a crucial role mediating migration of immune cells into the infarcted area. However, their value in long-term outcome prediction for patients with cerebrovascular diseases (CVD) is less described. Levels of four CAMs (E-selectin, P-selectin glycoprotein ligand-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1)) and six other known biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I, vasopressin-neurophysin 2-copeptin, and S100 calcium-binding protein B) were measured in a population of patients presenting CVD. Blood collections for analysis were performed within different time windows after stroke onset: 0-6 h, 6-36 h, 2-3 days, 5-7 days, and 2-3 weeks. Independent associations with poor outcome at 3 months (modified Rankin Scale score > 2) were sought using univariate and multivariate analysis after adjustments for age and National Institute of Health Stroke Scale score. Predictive ability of each biomarker has also been assessed with ROC analysis. One hundred patients were prospectively included whom 75 presented with ischemic strokes, nine with hemorrhagic strokes and 16 with transient ischemic attacks. During the first 6 h after stroke onset, E-selectin was found to be an independent predictor of 3-month outcome (odds ratio (OR) =24; 95 % confidence interval (95 % CI), 2-354; p = 0.022) (area under the curve (AUC) =78 %), as was VCAM-1 during the third week after onset (OR = 8; 95 % CI, 2-37; p = 0.01) (AUC = 73 %). Associations remained after the exclusion of patients with hemorrhagic strokes and transient ischemic attacks. Independent associations with outcome were also found for CRP (OR = 5; 95 % CI, 1-22; p = 0.023) and IL-6 (OR = 5; 95 % CI, 1-17; p = 0.021) at 2-3 days and for NT-proBNP at 6-36 h (OR = 20; 95 % CI, 1-337; p = 0.04). E-selectin and VCAM-1 were independent predictors of outcome in a population of patients with CVD. The predictive capability of other biomarkers known to be indicators for prognosis also emerged, confirming the study's robustness. CAMs levels could be considered as objective biological criteria for prognosis in CVD.