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Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function

Salzinger, Barbara ; Lundwall, Kristina ; Evans, Marie ; Mörtberg, Josefin ; Wallén, Håkan ; Jernberg, Tomas ; Kahan, Thomas ; Lundman, Pia ; Tornvall, Per and Erlinge, David LU orcid , et al. (2024) In Clinical Kidney Journal 17(3).
Abstract

Background. The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods. A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression... (More)

Background. The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods. A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results. The concentrations of nine biomarkers—endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)—were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19–1.50). None of the biomarkers showed an interaction with CKD. Conclusions. The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ACS, biomarkers, kidney function, prognosis
in
Clinical Kidney Journal
volume
17
issue
3
article number
sfae050
publisher
Oxford University Press
external identifiers
  • pmid:38524235
  • scopus:85188794365
ISSN
2048-8505
DOI
10.1093/ckj/sfae050
language
English
LU publication?
yes
id
28efb105-c170-4106-a59c-9ab2096ed899
date added to LUP
2024-04-12 14:10:41
date last changed
2024-04-26 16:09:22
@article{28efb105-c170-4106-a59c-9ab2096ed899,
  abstract     = {{<p>Background. The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods. A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results. The concentrations of nine biomarkers—endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)—were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19–1.50). None of the biomarkers showed an interaction with CKD. Conclusions. The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.</p>}},
  author       = {{Salzinger, Barbara and Lundwall, Kristina and Evans, Marie and Mörtberg, Josefin and Wallén, Håkan and Jernberg, Tomas and Kahan, Thomas and Lundman, Pia and Tornvall, Per and Erlinge, David and Lindahl, Bertil and Baron, Tomasz and Rezeli, Melinda and Spaak, Jonas and Jacobson, Stefan H.}},
  issn         = {{2048-8505}},
  keywords     = {{ACS; biomarkers; kidney function; prognosis}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical Kidney Journal}},
  title        = {{Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function}},
  url          = {{http://dx.doi.org/10.1093/ckj/sfae050}},
  doi          = {{10.1093/ckj/sfae050}},
  volume       = {{17}},
  year         = {{2024}},
}