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. 2023 Feb 15:373:64-71.
doi: 10.1016/j.ijcard.2022.12.005. Epub 2022 Dec 5.

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

Josefin Mörtberg  1 , Barbara Salzinger  2 , Kristina Lundwall  3 , Robert Edfors  3 , Stefan H Jacobson  2 , Håkan N Wallén  3 , Tomas Jernberg  3 , Tomasz Baron  4 , David Erlinge  5 , Pontus Andell  6 , Stefan James  4 , Kai M Eggers  4 , Marcus Hjort  4 , Thomas Kahan  3 , Pia Lundman  3 , Per Tornvall  7 , Melinda Rezeli  8 , György Marko-Varga  8 , Bertil Lindahl  4 , Jonas Spaak  3
Affiliations

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

Josefin Mörtberg et al. Int J Cardiol. .

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 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 m2 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 m2.

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.

Keywords: Proteomics; chronic renal insufficiency; endothelium; haemostasis; myocardial infarction; vascular.

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Conflict of interest statement

Declaration of Competing Interest Dr. Spaak has received speaker honoraria from AstraZeneca, Bayer, Medtronics and Novartis and declare minor share hold in Beat Vascular Health.

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