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Critical Care
Published in: Critical Care 6/2008

Open Access 01-12-2008 | Research

Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients

Authors: Philipp Kümpers, Alexander Lukasz, Sascha David, Rüdiger Horn, Carsten Hafer, Robert Faulhaber-Walter, Danilo Fliser, Hermann Haller, Jan T Kielstein

Published in: Critical Care | Issue 6/2008

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Abstract

Introduction

The endothelial specific angiopoietin (Ang)-Tie2 ligand-receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis. Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage, whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function. Here, we examine whether circulating Ang-1 and/or Ang-2 independently predict mortality in a cohort of critically ill medical patients.

Methods

Circulating vascular endothelial growth factor (VEGF), Ang-1 and Ang-2 were prospectively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay (IRMA) and ELISA, respectively. Survival after 30 days was the primary outcome studied.

Results

Median serum Ang-2 concentrations were increasingly higher across the following groups: healthy controls, patients without sepsis, patients with sepsis and patients with septic shock. In contrast, Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls. Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2), tissue hypoxia, Sequential Organ Failure Assessment (SOFA) and Physiology and Chronic Health Evaluation II (APACHE II) score. Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival.

Conclusions

A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients. Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness. Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU.
Appendix
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Metadata
Title
Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients
Authors
Philipp Kümpers
Alexander Lukasz
Sascha David
Rüdiger Horn
Carsten Hafer
Robert Faulhaber-Walter
Danilo Fliser
Hermann Haller
Jan T Kielstein
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7130

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