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Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function

Mörtberg, Josefin ; Salzinger, Barbara ; Lundwall, Kristina ; Edfors, Robert ; Jacobson, Stefan H ; Wallén, Håkan N ; Jernberg, Tomas ; Baron, Tomasz ; Erlinge, David LU orcid and Andell, Pontus LU , et al. (2023) In International Journal of Cardiology 373. p.64-71
Abstract

BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.

METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox... (More)

BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.

METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m
2 was tested.

RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m
2.

CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Prognosis, Acute Coronary Syndrome/diagnosis, Receptors, Urokinase Plasminogen Activator, Adrenomedullin, Hemostatics, Renin, Biomarkers, Kidney, Hemostasis
in
International Journal of Cardiology
volume
373
pages
8 pages
publisher
Elsevier
external identifiers
  • pmid:36476672
  • scopus:85143864021
ISSN
0167-5273
DOI
10.1016/j.ijcard.2022.12.005
language
English
LU publication?
yes
additional info
Copyright © 2022 Elsevier B.V. All rights reserved.
id
7df710a1-c677-463a-9e96-d8422bee2854
date added to LUP
2023-11-30 13:25:46
date last changed
2024-06-23 11:23:49
@article{7df710a1-c677-463a-9e96-d8422bee2854,
  abstract     = {{<p>BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.</p><p>METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m<br>
 2 was tested.<br>
 </p><p>RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m<br>
 2.<br>
 </p><p>CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.</p>}},
  author       = {{Mörtberg, Josefin and Salzinger, Barbara and Lundwall, Kristina and Edfors, Robert and Jacobson, Stefan H and Wallén, Håkan N and Jernberg, Tomas and Baron, Tomasz and Erlinge, David and Andell, Pontus and James, Stefan and Eggers, Kai M and Hjort, Marcus and Kahan, Thomas and Lundman, Pia and Tornvall, Per and Rezeli, Melinda and Marko-Varga, György and Lindahl, Bertil and Spaak, Jonas}},
  issn         = {{0167-5273}},
  keywords     = {{Humans; Prognosis; Acute Coronary Syndrome/diagnosis; Receptors, Urokinase Plasminogen Activator; Adrenomedullin; Hemostatics; Renin; Biomarkers; Kidney; Hemostasis}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{64--71}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Cardiology}},
  title        = {{Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function}},
  url          = {{http://dx.doi.org/10.1016/j.ijcard.2022.12.005}},
  doi          = {{10.1016/j.ijcard.2022.12.005}},
  volume       = {{373}},
  year         = {{2023}},
}