Elevated biomarkers of endothelial dysfunction/activation at ICU admission are associated with sepsis development

Cytokine. 2014 Oct;69(2):240-7. doi: 10.1016/j.cyto.2014.06.010. Epub 2014 Jul 12.


Widespread endothelial activation and dysfunction often precede clinical sepsis. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Such factors include endothelial adhesion molecules like E- and P-selectin, and the intercellular adhesion molecule-1, vascular endothelial cadherin, growth factors such as Angiopoietin-1 and -2 and vascular endothelial growth factor, as well as von Willebrand factor antigen. We sought to investigate whether circulating biomarkers of endothelial activation/dysfunction measured at ICU admission are associated with subsequent sepsis development. Eighty-nine critically-ill patients admitted to a general ICU who met no sepsis criteria were studied. Plasma or serum levels of the above-mentioned endothelium-derived molecules were measured during the first 24h post ICU; acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, age, sex, diagnostic category, and circulating procalcitonin (PCT) and C-reactive protein (CRP) levels were additionally measured or recorded. Forty-five patients subsequently became septic and 44 did not. Soluble (s) E- and P-selectin levels, circulating PCT, SOFA score and diagnostic category were significantly different between the two groups. Multiple logistic regression analysis associated elevated sE- and sP-selectin levels and SOFA with an increased risk of developing sepsis, while multiple Cox regression analysis identified sE- and sP-selectin levels as the only parameters related to sepsis appearance with time [RR=1.026, 95%CI=1.008-1.045, p=0.005; RR=1.005 (by 10 units), 95%CI=1.000-1.010, p=0.034, respectively]. When trauma patients were independently analyzed, multiple Cox regression analysis revealed sE-selectin to be the only molecule associated with sepsis development with time (RR=1.041, 95%CI: 1.019-1.065; p<0.001). In conclusion, in our cohort of initially non-septic critically-ill patients, high levels of the circulating endothelial adhesion molecules E- and P-selectin, measured at ICU admission, appear to be associated with sepsis development in time.

Keywords: Critically-ill; Prognostic; Selectin; Sepsis; Shedding.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Glycoproteins / blood
  • Hospitalization*
  • Humans
  • Intensive Care Units*
  • Intercellular Signaling Peptides and Proteins / blood
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • ROC Curve
  • Regression Analysis
  • Sepsis / blood*
  • Sepsis / diagnosis
  • Sepsis / microbiology
  • Solubility
  • Young Adult


  • Biomarkers
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins