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

Barbara Salzinger; Kristina Lundwall; Marie Evans; Josefin Mörtberg; Håkan Wallén; Tomas Jernberg; Thomas Kahan; Pia Lundman; Per Tornvall; David Erlinge; Bertil Lindahl; Tomasz Baron; Melinda Rezeli; Jonas Spaak; Stefan H Jacobson

doi:10.1093/ckj/sfae050

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

Clin Kidney J. 2024 Mar 1;17(3):sfae050. doi: 10.1093/ckj/sfae050. eCollection 2024 Mar.

Authors

Affiliations

¹ Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
² Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
³ ME Renal Medicine, Department of Clinical Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
⁴ Division of Nephrology, Department of Internal Medicine, Centre for Clinical Research, County of Vastmanland and Uppsala University, Uppsala, Sweden.
⁵ Department of Clinical Science and Education, Sodersjukhuset, Karolinska Institute, Stockholm, Sweden.
⁶ Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
⁷ Department of Medical Sciences, Cardiology, Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.
⁸ Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden.

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 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.

Keywords: ACS; biomarkers; kidney function; prognosis.