Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

TY - JOUR

T1 - Profound Endothelial Damage Predicts Impending Organ Failure and Death in Sepsis

AU - Johansen, Maria E

AU - Johansson, Pär I.

AU - Ostrowski, Sisse R

AU - Bestle, Morten H

AU - Hein, Lars

AU - Jensen, Anne L G

AU - Søe-Jensen, Peter

AU - Andersen, Mads H

AU - Steensen, Morten

AU - Mohr, Thomas

AU - Thormar, Katrin

AU - Lundgren, Bettina

AU - Cozzi-Lepri, Alessandro

AU - Lundgren, Jens D

AU - Jensen, Jens-Ulrik

N1 - Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels on death and organ failures during follow-up were assessed in Cox models adjusted for potential confounders including key organ dysfunction measures assessed at enrollment. Of the 1,103 included patients, 418 died. sTM levels at the time of enrollment independently predicted risk of death in adjusted models (hazard ratio [HR] [highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence interval [CI]: 1.2-4.0], p = 0.02, respectively). Conversely, syndecan-1 levels failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6-1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95% CI: 1.5-8.3], p = 0.005 and 2.0 [95% CI: 0.8-5.0], p = 0.1321, respectively). Profound damage to the endothelium independently predicts risk of multiple organ failure and death in septic patients. Our findings also suggest that the detrimental effect of profound endothelial damage on risk of death operates via mechanisms other than causing organ failures per se. Therefore, damage to the endothelium appears centrally involved in the pathogenesis of death in sepsis and could be a target for intervention.

AB - Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels on death and organ failures during follow-up were assessed in Cox models adjusted for potential confounders including key organ dysfunction measures assessed at enrollment. Of the 1,103 included patients, 418 died. sTM levels at the time of enrollment independently predicted risk of death in adjusted models (hazard ratio [HR] [highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence interval [CI]: 1.2-4.0], p = 0.02, respectively). Conversely, syndecan-1 levels failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6-1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95% CI: 1.5-8.3], p = 0.005 and 2.0 [95% CI: 0.8-5.0], p = 0.1321, respectively). Profound damage to the endothelium independently predicts risk of multiple organ failure and death in septic patients. Our findings also suggest that the detrimental effect of profound endothelial damage on risk of death operates via mechanisms other than causing organ failures per se. Therefore, damage to the endothelium appears centrally involved in the pathogenesis of death in sepsis and could be a target for intervention.

KW - Aged

KW - Biomarkers

KW - Endothelium, Vascular

KW - Female

KW - Humans

KW - Male

KW - Multiple Organ Failure

KW - Predictive Value of Tests

KW - Prognosis

KW - Sepsis

KW - Syndecan-1

KW - Thrombomodulin

U2 - 10.1055/s-0034-1398377

DO - 10.1055/s-0034-1398377

M3 - Journal article

C2 - 25590523

SN - 0094-6176

VL - 41

SP - 16

EP - 25

JO - Seminars in Thrombosis and Hemostasis

JF - Seminars in Thrombosis and Hemostasis

IS - 1

ER -