An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.

Winnie Chua, Victor R Cardoso, Eduard Guasch, Moritz F Sinner, Christoph Al-Taie, Paul Brady, Barbara Casadei, Harry J G M Crijns, Elton A M P Dudink, Stéphane N Hatem, Stefan Kääb, Peter Kastner, Lluis Mont, Frantisek Nehaj, Yanish Purmah, Jasmeet S Reyat, Ulrich Schotten, Laura C Sommerfeld, Stef Zeemering, André Ziegler, Georgios V Gkoutos, Paulus Kirchhof, Larissa Fabritz

Journal: Scientific reports 2023;13(1):16743

PMID: 37798357

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Abstract

Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.

Address: Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.; MRC Health Data Research UK (HDR), Midlands Site, London, UK.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; Hospital Clinic de Barcelona, Institute of Biomedical Research August Pi Sunyer (IDIBAPS), Barcelona, Spain.; Department of Medicine I, University Hospital, LMU, Munich, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site: Munich Heart Alliance, Munich, Germany.; University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, UKE Martinistrasse 52, 20246, Hamburg, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany.; Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.; Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.; University of Oxford, Oxford, UK.; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.; IHU-ICAN Institute of Cardiometabolism and Nutrition, Paris, France.; Roche Diagnostics GmbH, Penzberg, Germany.; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.; University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, UKE Martinistrasse 52, 20246, Hamburg, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany.; Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Roche Diagnostics International AG, Rotkreuz, Switzerland.; MRC Health Data Research UK (HDR), Midlands Site, London, UK.; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.; German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany.; Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK. [email protected].; University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, UKE Martinistrasse 52, 20246, Hamburg, Germany. [email protected].; German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany. [email protected].; Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [email protected].

DOI: 10.1038/s41598-023-42331-7

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MeSH Terms: Humans, Male, Aged, Female, Atrial Fibrillation, Angiopoietin-2, Cross-Sectional Studies, Biomarkers, Stroke, Risk Factors, Bone Morphogenetic Proteins