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Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients

Lundberg, Oscar LU orcid ; Bergenzaun, Lill LU ; Rydén, Jörgen ; Rosenqvist, Mari LU ; Melander, Olle LU orcid and Chew, Michelle S. LU (2016) In Critical Care 20(1).
Abstract
Abstract

Background
Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal... (More)
Abstract

Background
Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.

Methods
A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.

Results
Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.

Conclusions
MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.

Keywords: Sepsis, Shock, Adrenomedullin, Endothelin-1, High-sensitivity troponin, Echocardiography, Myocardial injury, Mortality, Likelihood ratio (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adrenomedullin, Echocardiography, Endothelin-1, High-sensitivity troponin, Likelihood ratio, Mortality, Myocardial injury, Sepsis, Shock
in
Critical Care
volume
20
issue
1
article number
178
publisher
BioMed Central (BMC)
external identifiers
  • scopus:84975165804
  • pmid:27282767
  • wos:000377718800001
ISSN
1364-8535
DOI
10.1186/s13054-016-1361-y
language
English
LU publication?
yes
id
970a0750-3f13-4ea7-8364-941c04569ac2
date added to LUP
2016-07-04 10:04:17
date last changed
2024-09-07 18:03:18
@article{970a0750-3f13-4ea7-8364-941c04569ac2,
  abstract     = {{Abstract<br/><br/>Background<br/>Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.<br/><br/>Methods<br/>A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.<br/><br/>Results<br/>Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.<br/><br/>Conclusions<br/>MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.<br/><br/>Keywords: Sepsis, Shock, Adrenomedullin, Endothelin-1, High-sensitivity troponin, Echocardiography, Myocardial injury, Mortality, Likelihood ratio}},
  author       = {{Lundberg, Oscar and Bergenzaun, Lill and Rydén, Jörgen and Rosenqvist, Mari and Melander, Olle and Chew, Michelle S.}},
  issn         = {{1364-8535}},
  keywords     = {{Adrenomedullin; Echocardiography; Endothelin-1; High-sensitivity troponin; Likelihood ratio; Mortality; Myocardial injury; Sepsis; Shock}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Critical Care}},
  title        = {{Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients}},
  url          = {{http://dx.doi.org/10.1186/s13054-016-1361-y}},
  doi          = {{10.1186/s13054-016-1361-y}},
  volume       = {{20}},
  year         = {{2016}},
}