Comprehensive assessment of novel cardiovascular biomarkers in AF

Amelie H Ohlrogge; Daniel Engler; Patricia Schlieker; Ferdinand Seum; Kim Rosebrock; Nicole Nebel; Dora Csengeri; Larissa Fabritz; André Ziegler; Stefan Blankenberg; Paulus Kirchhof; Tanja Zeller; Renate B Schnabel

doi:10.1093/europace/euag096

Comprehensive assessment of novel cardiovascular biomarkers in AF

Amelie H Ohlrogge, Daniel Engler, Patricia Schlieker, Ferdinand Seum, Kim Rosebrock, Nicole Nebel, Dora Csengeri, Larissa Fabritz, André Ziegler, Stefan Blankenberg, Paulus Kirchhof, Tanja Zeller, Renate B Schnabel

Institut für Kardiogenetik

Abstract

AIMS: Biomarkers have the potential to improve risk prediction beyond clinical characteristics. We examined the association of four emerging cardiovascular biomarkers [angiopoietin 2 (Angpt2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), insulin-like growth factor binding protein 7 (IGFBP7)] in comparison with N-terminal pro B-type natriuretic peptide (NT-proBNP) across the disease course of atrial fibrillation (AF).

METHODS AND RESULTS: We enrolled patients from a prospective cohort of patients at risk of AF or with manifest arrhythmia. The circulating vascular biomarkers were quantified using high-throughput, high-precision precommercial assays (Roche Diagnostics). A combined endpoint comprised: stroke, transient ischaemic attack (TIA), myocardial infarction, incident coronary heart disease, heart failure, and all-cause mortality. Of the total n = 1047 individuals, n = 527 had prevalent AF, and n = 507 were free of AF at baseline. Median follow-up was 42 months. A total of n = 66 individuals died; the combined endpoint occurred in n = 198 individuals. All five biomarkers were significantly associated with the incidence of AF, both in multistate analysis (MSA) and Cox regression, although the association with FGF23 was only significant in the age- and sex-adjusted Cox model. AF recurrence was significantly associated with all biomarkers, most strongly with NT-proBNP. In prevalent AF, NT-proBNP, FGF23, and IGFBP7 were associated with the combined endpoint and all-cause mortality, and Angpt2 was associated with all-cause mortality. NT-proBNP showed the strongest association for all-cause mortality, and IGFBP7 for the combined endpoint in prevalent AF. In incident AF the association with the combined outcome was statistically significant for NT-proBNP in multivariable-adjusted models. All-cause mortality in individuals with incident AF was associated with NT-proBNP, Angpt2, FGF23, and IGFBP7 both in the MSA and Cox model.

CONCLUSION: All novel biomarkers Angpt2, BMP10, FGF23, and IGFBP7 showed predictive value for incident and recurrent AF. Individual biomarkers showed distinct strengths in prediction of outcomes across the disease spectrum of AF.

Originalsprache	Englisch
Zeitschrift	Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
Jahrgang	28
Ausgabenummer	5
ISSN	1099-5129
DOIs	https://doi.org/10.1093/europace/euag096
Publikationsstatus	Veröffentlicht - 06.05.2026

Fördermittel

We acknowledge financial support from the Open Access Publication Fund of UKE - Universitätsklinikum Hamburg-Eppendorf. A.H.O. is supported by the German Heart Foundation/German Foundation of Heart Research. D.C. received a research grant from the Wolfgang Seefried Project funding of the German Heart Foundation. L.F. acknowledges support by European Union grant agreement 633196 (CATCH ME), grant agreement 847770 (AFFECT-AF), and European Union grant agreement 965286 (MAESTRIA), British Heart Foundation (AA/18/2/34218), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK), and the National Institute for Health and Care Research (NIHR). P.K. has been partially supported by European Union (BigData@Heart, grant agreement EU IMI 116074; AFFECT-AF, grant agreement 847770; MAESTRIA,grant agreement 965286), British Heart Foundation (PG/17/30/32961 and PG/20/22/35093; AA/18/2/34218), German Centre for Cardiovascular Research supported by the German Federal Ministry of Education and Research (DZHK), and Leducq Foundation. R.B.S. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under the grant agreement 648131, from the European Union’s Horizon 2020 research and innovation programme under the grant agreement 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114), and from the German Federal Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). A.H.O. is supported by the German Heart Foundation/German Foundation of Heart Research. D.C. received a research grant from the Wolfgang Seefried Project funding of the German Heart Foundation. L.F. acknowledges support by European Union grant agreement 633196 (CATCH ME), grant agreement 847770 (AFFECT-AF), and European Union grant agreement 965286 (MAESTRIA), British Heart Foundation (AA/18/2/34218), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK), and the National Institute for Health and Care Research (NIHR). P.K. has been partially supported by European Union (BigData@Heart, grant agreement EU IMI 116074; AFFECT-AF, grant agreement 847770; MAESTRIA,grant agreement 965286), British Heart Foundation (PG/17/30/32961 and PG/20/22/35093; AA/18/2/34218), German Centre for Cardiovascular Research supported by the German Federal Ministry of Education and Research (DZHK), and Leducq Foundation. R.B.S. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under the grant agreement 648131, from the European Union’s Horizon 2020 research and innovation programme under the grant agreement 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114), and from the German Federal Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). We acknowledge financial support from the Open Access Publication Fund of UKE - Universitätsklinikum Hamburg-Eppendorf.

Träger	Trägernummer
Deutsche Herzstiftung
National Institute for Health and Care Research
Deutsche Stiftung für Herzforschung
Deutsches Zentrum für Herz-Kreislaufforschung
AFFECT-EU
Universitätsklinikum Hamburg-Eppendorf
Fondation Leducq
European Research Council
Bundesministerium für Forschung, Technologie und Raumfahrt	01ZX1408A, ERACoSysMed3, 031L0239
Horizon 2020 Framework Programme	648131
European Commission	847770, 633196, 965286, IMI 116074
British Heart Foundation	AA/18/2/34218
AFFECT-AF	PG/20/22/35093, PG/17/30/32961
EU	IMI 116074
German Center for Cardiovascular Research	81Z1710103, 81Z0710114

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Zentren: Universitäres Herzzentrum Lübeck (UHZL)
Querschnittsbereich: Medizinische Genetik

DFG-Fachsystematik

2.22-12 Kardiologie, Angiologie
2.22-03 Humangenetik
2.11-05 Allgemeine Genetik und funktionelle Genomforschung

Dokumente

10.1093/europace/euag096

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Ohlrogge, A. H., Engler, D., Schlieker, P., Seum, F., Rosebrock, K., Nebel, N., Csengeri, D., Fabritz, L., Ziegler, A., Blankenberg, S., Kirchhof, P., Zeller, T., & Schnabel, R. B. (2026). Comprehensive assessment of novel cardiovascular biomarkers in AF. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 28(5). https://doi.org/10.1093/europace/euag096

Ohlrogge, Amelie H ; Engler, Daniel ; Schlieker, Patricia et al. / Comprehensive assessment of novel cardiovascular biomarkers in AF. in: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2026 ; Jahrgang 28, Nr. 5.

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abstract = "AIMS: Biomarkers have the potential to improve risk prediction beyond clinical characteristics. We examined the association of four emerging cardiovascular biomarkers [angiopoietin 2 (Angpt2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), insulin-like growth factor binding protein 7 (IGFBP7)] in comparison with N-terminal pro B-type natriuretic peptide (NT-proBNP) across the disease course of atrial fibrillation (AF).METHODS AND RESULTS: We enrolled patients from a prospective cohort of patients at risk of AF or with manifest arrhythmia. The circulating vascular biomarkers were quantified using high-throughput, high-precision precommercial assays (Roche Diagnostics). A combined endpoint comprised: stroke, transient ischaemic attack (TIA), myocardial infarction, incident coronary heart disease, heart failure, and all-cause mortality. Of the total n = 1047 individuals, n = 527 had prevalent AF, and n = 507 were free of AF at baseline. Median follow-up was 42 months. A total of n = 66 individuals died; the combined endpoint occurred in n = 198 individuals. All five biomarkers were significantly associated with the incidence of AF, both in multistate analysis (MSA) and Cox regression, although the association with FGF23 was only significant in the age- and sex-adjusted Cox model. AF recurrence was significantly associated with all biomarkers, most strongly with NT-proBNP. In prevalent AF, NT-proBNP, FGF23, and IGFBP7 were associated with the combined endpoint and all-cause mortality, and Angpt2 was associated with all-cause mortality. NT-proBNP showed the strongest association for all-cause mortality, and IGFBP7 for the combined endpoint in prevalent AF. In incident AF the association with the combined outcome was statistically significant for NT-proBNP in multivariable-adjusted models. All-cause mortality in individuals with incident AF was associated with NT-proBNP, Angpt2, FGF23, and IGFBP7 both in the MSA and Cox model.CONCLUSION: All novel biomarkers Angpt2, BMP10, FGF23, and IGFBP7 showed predictive value for incident and recurrent AF. Individual biomarkers showed distinct strengths in prediction of outcomes across the disease spectrum of AF.",

author = "Ohlrogge, \{Amelie H\} and Daniel Engler and Patricia Schlieker and Ferdinand Seum and Kim Rosebrock and Nicole Nebel and Dora Csengeri and Larissa Fabritz and Andr{\'e} Ziegler and Stefan Blankenberg and Paulus Kirchhof and Tanja Zeller and Schnabel, \{Renate B\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.",

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journal = "Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",

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Ohlrogge, AH, Engler, D, Schlieker, P, Seum, F, Rosebrock, K, Nebel, N, Csengeri, D, Fabritz, L, Ziegler, A, Blankenberg, S, Kirchhof, P, Zeller, T & Schnabel, RB 2026, 'Comprehensive assessment of novel cardiovascular biomarkers in AF', Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Jg. 28, Nr. 5. https://doi.org/10.1093/europace/euag096

Comprehensive assessment of novel cardiovascular biomarkers in AF. / Ohlrogge, Amelie H; Engler, Daniel; Schlieker, Patricia et al.
in: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Jahrgang 28, Nr. 5, 06.05.2026.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Comprehensive assessment of novel cardiovascular biomarkers in AF

AU - Ohlrogge, Amelie H

AU - Engler, Daniel

AU - Schlieker, Patricia

AU - Seum, Ferdinand

AU - Rosebrock, Kim

AU - Nebel, Nicole

AU - Csengeri, Dora

AU - Fabritz, Larissa

AU - Ziegler, André

AU - Blankenberg, Stefan

AU - Kirchhof, Paulus

AU - Zeller, Tanja

AU - Schnabel, Renate B

N1 - Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

PY - 2026/5/6

Y1 - 2026/5/6

N2 - AIMS: Biomarkers have the potential to improve risk prediction beyond clinical characteristics. We examined the association of four emerging cardiovascular biomarkers [angiopoietin 2 (Angpt2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), insulin-like growth factor binding protein 7 (IGFBP7)] in comparison with N-terminal pro B-type natriuretic peptide (NT-proBNP) across the disease course of atrial fibrillation (AF).METHODS AND RESULTS: We enrolled patients from a prospective cohort of patients at risk of AF or with manifest arrhythmia. The circulating vascular biomarkers were quantified using high-throughput, high-precision precommercial assays (Roche Diagnostics). A combined endpoint comprised: stroke, transient ischaemic attack (TIA), myocardial infarction, incident coronary heart disease, heart failure, and all-cause mortality. Of the total n = 1047 individuals, n = 527 had prevalent AF, and n = 507 were free of AF at baseline. Median follow-up was 42 months. A total of n = 66 individuals died; the combined endpoint occurred in n = 198 individuals. All five biomarkers were significantly associated with the incidence of AF, both in multistate analysis (MSA) and Cox regression, although the association with FGF23 was only significant in the age- and sex-adjusted Cox model. AF recurrence was significantly associated with all biomarkers, most strongly with NT-proBNP. In prevalent AF, NT-proBNP, FGF23, and IGFBP7 were associated with the combined endpoint and all-cause mortality, and Angpt2 was associated with all-cause mortality. NT-proBNP showed the strongest association for all-cause mortality, and IGFBP7 for the combined endpoint in prevalent AF. In incident AF the association with the combined outcome was statistically significant for NT-proBNP in multivariable-adjusted models. All-cause mortality in individuals with incident AF was associated with NT-proBNP, Angpt2, FGF23, and IGFBP7 both in the MSA and Cox model.CONCLUSION: All novel biomarkers Angpt2, BMP10, FGF23, and IGFBP7 showed predictive value for incident and recurrent AF. Individual biomarkers showed distinct strengths in prediction of outcomes across the disease spectrum of AF.

AB - AIMS: Biomarkers have the potential to improve risk prediction beyond clinical characteristics. We examined the association of four emerging cardiovascular biomarkers [angiopoietin 2 (Angpt2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), insulin-like growth factor binding protein 7 (IGFBP7)] in comparison with N-terminal pro B-type natriuretic peptide (NT-proBNP) across the disease course of atrial fibrillation (AF).METHODS AND RESULTS: We enrolled patients from a prospective cohort of patients at risk of AF or with manifest arrhythmia. The circulating vascular biomarkers were quantified using high-throughput, high-precision precommercial assays (Roche Diagnostics). A combined endpoint comprised: stroke, transient ischaemic attack (TIA), myocardial infarction, incident coronary heart disease, heart failure, and all-cause mortality. Of the total n = 1047 individuals, n = 527 had prevalent AF, and n = 507 were free of AF at baseline. Median follow-up was 42 months. A total of n = 66 individuals died; the combined endpoint occurred in n = 198 individuals. All five biomarkers were significantly associated with the incidence of AF, both in multistate analysis (MSA) and Cox regression, although the association with FGF23 was only significant in the age- and sex-adjusted Cox model. AF recurrence was significantly associated with all biomarkers, most strongly with NT-proBNP. In prevalent AF, NT-proBNP, FGF23, and IGFBP7 were associated with the combined endpoint and all-cause mortality, and Angpt2 was associated with all-cause mortality. NT-proBNP showed the strongest association for all-cause mortality, and IGFBP7 for the combined endpoint in prevalent AF. In incident AF the association with the combined outcome was statistically significant for NT-proBNP in multivariable-adjusted models. All-cause mortality in individuals with incident AF was associated with NT-proBNP, Angpt2, FGF23, and IGFBP7 both in the MSA and Cox model.CONCLUSION: All novel biomarkers Angpt2, BMP10, FGF23, and IGFBP7 showed predictive value for incident and recurrent AF. Individual biomarkers showed distinct strengths in prediction of outcomes across the disease spectrum of AF.

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UR - https://www.mendeley.com/catalogue/9a86aaa4-0ec3-3a86-b40d-3b3335484202/

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DO - 10.1093/europace/euag096

M3 - Journal articles

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JO - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

JF - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

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Ohlrogge AH, Engler D, Schlieker P, Seum F, Rosebrock K, Nebel N et al. Comprehensive assessment of novel cardiovascular biomarkers in AF. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2026 Mai 6;28(5). doi: 10.1093/europace/euag096

Comprehensive assessment of novel cardiovascular biomarkers in AF

Abstract

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UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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