C-terminal proendothelin-1 (CT-proET-1) is associated with organ failure and predicts mortality in critically ill patients.
BACKGROUND
Endothelin 1 (ET-1) is a strong vasoconstrictor, which is involved in inflammation and reduced tissue perfusion. C-terminal proendothelin-1 (CT-proET-1) is the stable circulating precursor protein of ET-1. We hypothesized that CT-proET-1, reflecting ET-1 activation, is involved in the pathogenesis of critical illness and associated with its prognosis.


METHODS
Two hundred seventeen critically ill patients (144 with sepsis, 73 without sepsis) were included prospectively upon admission to the medical intensive care unit (ICU), in comparison to 65 healthy controls. CT-proET-1 serum concentrations were correlated with clinical data and extensive laboratory parameters. Overall survival was followed for up to 3 years.


RESULTS
CT-proET-1 serum levels at admission were significantly increased in critically ill patients compared to controls. CT-proET-1 serum levels showed significant correlations to systemic inflammation as well as multiple markers of organ dysfunction (kidney, liver, heart). Patients with sepsis displayed higher circulating CT-proET-1 than ICU patients with non-septic diseases. CT-proET-1 levels >74 pmol/L at ICU admission independently predicted ICU death (adjusted hazard ratio (HR) 2.66, 95% confidence interval (CI) 1.30-5.47) and overall mortality during follow-up (adjusted HR 2.19, 95%-CI 1.21-3.98).


CONCLUSIONS
CT-proET-1 serum concentrations at admission are increased in critically ill patients and associated with sepsis, disease severity, organ failure, and mortality.
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Lukas
L
Buendgens
Medical Care Center, Dr. Stein and Colleagues, 41061 Mönchengladbach, Germany.
Eray
E
Yagmur
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Jan
J
Bruensing
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Ulf
U
Herbers
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Christer
C
Baeck
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Christian
C
Trautwein
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Alexander
A
Koch
Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Frank
F
Tacke
Biomarker; C-terminal proendothelin-1; CT-proET-1; Critical illness; ET-1; Endothelin; ICU; Prognosis; Sepsis