Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction
Abstract Aims Besides regulating calcium‐phosphate metabolism, fibroblast growth factor 23 (FGF‐23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF‐23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study wa...
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Format: | Article |
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Wiley
2020-10-01
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Series: | ESC Heart Failure |
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Online Access: | https://doi.org/10.1002/ehf2.12816 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clotilde Roy Sibille Lejeune Alisson Slimani Christophe deMeester Sylvie A. Ahn AS Michel F. Rousseau Amzulescu Mihaela Audrey Ginion Benjamin Ferracin Agnès Pasquet David Vancraeynest Christophe Beauloye Jean‐Louis Vanoverschelde Sandrine Horman Damien Gruson Bernhard L. Gerber Anne‐Catherine Pouleur |
spellingShingle |
Clotilde Roy Sibille Lejeune Alisson Slimani Christophe deMeester Sylvie A. Ahn AS Michel F. Rousseau Amzulescu Mihaela Audrey Ginion Benjamin Ferracin Agnès Pasquet David Vancraeynest Christophe Beauloye Jean‐Louis Vanoverschelde Sandrine Horman Damien Gruson Bernhard L. Gerber Anne‐Catherine Pouleur Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction ESC Heart Failure FGF‐23 Biomarker Troponin Mortality NT‐proBNP Heart failure |
author_facet |
Clotilde Roy Sibille Lejeune Alisson Slimani Christophe deMeester Sylvie A. Ahn AS Michel F. Rousseau Amzulescu Mihaela Audrey Ginion Benjamin Ferracin Agnès Pasquet David Vancraeynest Christophe Beauloye Jean‐Louis Vanoverschelde Sandrine Horman Damien Gruson Bernhard L. Gerber Anne‐Catherine Pouleur |
author_sort |
Clotilde Roy |
title |
Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
title_short |
Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
title_full |
Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
title_fullStr |
Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
title_full_unstemmed |
Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
title_sort |
fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction |
publisher |
Wiley |
series |
ESC Heart Failure |
issn |
2055-5822 |
publishDate |
2020-10-01 |
description |
Abstract Aims Besides regulating calcium‐phosphate metabolism, fibroblast growth factor 23 (FGF‐23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF‐23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF‐23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients. Methods and results We prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two‐dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF‐23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF‐23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all‐cause mortality and first HF hospitalization and a secondary endpoint of all‐cause mortality. Median FGF‐23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P < 0.001). Among HFpEF patients, higher FGF‐23 levels were associated with female sex, higher incidence of atrial fibrillation, lower haemoglobin, worse renal function, and higher N terminal pro brain natriuretic peptide levels (P for trend < 0.05 for all). Regarding imaging characteristics, patients with higher FGF‐23 levels had greater left atrial volumes, worse right ventricular systolic function, and more fibrosis estimated by ECV (P for trend < 0.05 for all). FGF‐23 was moderately correlated with ECV (r = 0.46, P < 0.001). Over a mean follow‐up of 30 ± 8 months, 43 patients (31%) died and 69 patients (49%) were hospitalized for HF. A total of 87 patients (62%) reached the primary composite endpoint of all‐cause mortality and/or first HF hospitalization. In multivariate Cox regression analysis for the primary endpoint, FGF‐23 (HR: 3.44 [2.01; 5.90], P < 0.001) and E wave velocities (HR: 1.01 [1.00; 1.02], P = 0.034) were independent predictors of the primary composite endpoint. In multivariate Cox regression analysis for the secondary endpoint, ferritin (HR: 1.02 [1.01; 1.03], P < 0.001), FGF‐23 (HR: 2.85 [1.26; 6.44], P = 0.012), and ECV (HR: 1.26 [1.03; 1.23], P = 0.008) were independent predictors of all‐cause mortality. Conclusions Fibroblast growth factor 23 (FGF‐23) levels were significantly higher in HFpEF patients compared with controls of similar age and gender. FGF‐23 was correlated with fibrosis evaluated by ECV. High levels of FGF‐23 were significantly associated with signs of disease severity such as worse renal function, larger left atrial volumes, and right ventricular dysfunction. Moreover, FGF‐23 was a strong predictor of poor outcome (mortality and first HF hospitalization). |
topic |
FGF‐23 Biomarker Troponin Mortality NT‐proBNP Heart failure |
url |
https://doi.org/10.1002/ehf2.12816 |
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doaj-3417b308f50142b5947c259143c740b02021-06-02T08:45:54ZengWileyESC Heart Failure2055-58222020-10-01752494250710.1002/ehf2.12816Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fractionClotilde Roy0Sibille Lejeune1Alisson Slimani2Christophe deMeester3Sylvie A. Ahn AS4Michel F. Rousseau5Amzulescu Mihaela6Audrey Ginion7Benjamin Ferracin8Agnès Pasquet9David Vancraeynest10Christophe Beauloye11Jean‐Louis Vanoverschelde12Sandrine Horman13Damien Gruson14Bernhard L. Gerber15Anne‐Catherine Pouleur16Division of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumPôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC) Université Catholique de Louvain Brussels BelgiumClinical Biology Department Cliniques Universitaires St Luc, Université catholique de Louvain Brussels BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumPôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC) Université Catholique de Louvain Brussels BelgiumClinical Biology Department Cliniques Universitaires St Luc, Université catholique de Louvain Brussels BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumDivision of Cardiology, Department of Cardiovascular Diseases Cliniques Universitaires St. Luc Avenue Hippocrate, 10 Brussels 1200 BelgiumAbstract Aims Besides regulating calcium‐phosphate metabolism, fibroblast growth factor 23 (FGF‐23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF‐23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF‐23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients. Methods and results We prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two‐dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF‐23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF‐23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all‐cause mortality and first HF hospitalization and a secondary endpoint of all‐cause mortality. Median FGF‐23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P < 0.001). Among HFpEF patients, higher FGF‐23 levels were associated with female sex, higher incidence of atrial fibrillation, lower haemoglobin, worse renal function, and higher N terminal pro brain natriuretic peptide levels (P for trend < 0.05 for all). Regarding imaging characteristics, patients with higher FGF‐23 levels had greater left atrial volumes, worse right ventricular systolic function, and more fibrosis estimated by ECV (P for trend < 0.05 for all). FGF‐23 was moderately correlated with ECV (r = 0.46, P < 0.001). Over a mean follow‐up of 30 ± 8 months, 43 patients (31%) died and 69 patients (49%) were hospitalized for HF. A total of 87 patients (62%) reached the primary composite endpoint of all‐cause mortality and/or first HF hospitalization. In multivariate Cox regression analysis for the primary endpoint, FGF‐23 (HR: 3.44 [2.01; 5.90], P < 0.001) and E wave velocities (HR: 1.01 [1.00; 1.02], P = 0.034) were independent predictors of the primary composite endpoint. In multivariate Cox regression analysis for the secondary endpoint, ferritin (HR: 1.02 [1.01; 1.03], P < 0.001), FGF‐23 (HR: 2.85 [1.26; 6.44], P = 0.012), and ECV (HR: 1.26 [1.03; 1.23], P = 0.008) were independent predictors of all‐cause mortality. Conclusions Fibroblast growth factor 23 (FGF‐23) levels were significantly higher in HFpEF patients compared with controls of similar age and gender. FGF‐23 was correlated with fibrosis evaluated by ECV. High levels of FGF‐23 were significantly associated with signs of disease severity such as worse renal function, larger left atrial volumes, and right ventricular dysfunction. Moreover, FGF‐23 was a strong predictor of poor outcome (mortality and first HF hospitalization).https://doi.org/10.1002/ehf2.12816FGF‐23BiomarkerTroponinMortalityNT‐proBNPHeart failure |