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Updated: Oct 25, 2025
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial
Tymon Pol1,2, Ziad Hijazi1,2, Johan Lindbäck2
1Department of Medical Sciences, Cardiology, Uppsala University, Uppsala Science Park, SE-752 37 Uppsala, Sweden.
Aims:
Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.
Methods And Results:
A case-cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37-1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35-1.88)], interleukin-6 [IL-6; 1.29 (1.13-1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10-1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10-1.33)], urokinase receptor [uPAR; 1.38 (1.16-1.64)], trefoil factor 3 [TFF3; 1.27 (1.10-1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01-1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04-1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07-1.39)].
Conclusion:
In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.
Clinicaltrials.Gov Identifier:
NCT00412984 and NCT00262600.
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