Jozine M Ter Maaten1, Adriaan A Voors2, Kevin Damman1, Peter van der Meer1, Stefan D Anker3, John G Cleland4, Kenneth Dickstein5, Gerasimos Filippatos6, Pim van der Harst1, Hans L Hillege1, Chim C Lang7, Marco Metra8, Gerjan Navis9, Leong Ng10, Wouter Ouwerkerk11, Piotr Ponikowski12, Nilesh J Samani10, Dirk J van Veldhuisen1, Faiez Zannad13, Aeilko H Zwinderman11, Martin H de Borst9. 1. Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 2. Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: a.a.voors@umcg.nl. 3. Innovative Clinical Trials, Department of Cardiology & Pneumology, University Medical Center Göttingen, Göttingen, Germany. 4. National Heart & Lung Institute, Royal Brompton & Harefield hospitals, Imperial College, London, UK. 5. University of Bergen, Bergen, Norway; University of Stavanger, Stavanger, Norway. 6. National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 7. Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK. 8. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy. 9. Department of Nephrology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. 10. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. 11. Department of Epidemiology, Biostatistics & Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands. 12. Department of Heart Diseases, Wroclaw Medical University, Poland and Cardiology Department, Military Hospital, Wroclaw, Poland. 13. Inserm CIC1433, Université de Lorrain, CHU de Nancy, Nancy, France.
Abstract
BACKGROUND: Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). METHODS: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial. The association between FGF23 and outcome was evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: Median FGF23 was 218.0 [IQR: 117.1-579.3] RU/ml; patients with higher FGF23 levels had a worse NYHA class, more signs of congestion, and were less likely to use an ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARBs) at baseline (all P<0.01). Higher FGF23 levels were independently associated with higher BNP, lower eGFR, the presence of oedema and atrial fibrillation (all P<0.001). In addition, higher FGF23 was independently associated with impaired uptitration of ACEi/ARBs after 3months, but not of beta-blockers. In multivariable Cox regression analysis, FGF23 was independently associated with all-cause mortality (hazard ratio: 1.17 (1.09-1.26) per log increase, P<0.001), and the combined endpoint of all-cause mortality and HF hospitalization (1.15 (1.08-1.22) per log increase, P<0.001). CONCLUSIONS: In patients with new-onset and worsening HF, higher plasma FGF23 levels were independently associated with volume overload, less successful uptitration of ACEi/ARBs and an increased risk of all-cause mortality and HF hospitalization.
BACKGROUND:Fibroblast growth factor (FGF) 23 is a hormone that increases urinary phosphate excretion and regulates renal sodium reabsorption and plasma volume. We studied the role of plasma FGF23 in therapy optimization and outcomes in patients with new-onset and worsening heart failure (HF). METHODS: We measured plasma C-terminal FGF23 levels at baseline in 2399 of the 2516 patients included in the BIOlogy Study to Tailored Treatment in Chronic HF (BIOSTAT-CHF) trial. The association between FGF23 and outcome was evaluated by Cox regression analysis adjusted for potential confounders. RESULTS: Median FGF23 was 218.0 [IQR: 117.1-579.3] RU/ml; patients with higher FGF23 levels had a worse NYHA class, more signs of congestion, and were less likely to use an ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARBs) at baseline (all P<0.01). Higher FGF23 levels were independently associated with higher BNP, lower eGFR, the presence of oedema and atrial fibrillation (all P<0.001). In addition, higher FGF23 was independently associated with impaired uptitration of ACEi/ARBs after 3months, but not of beta-blockers. In multivariable Cox regression analysis, FGF23 was independently associated with all-cause mortality (hazard ratio: 1.17 (1.09-1.26) per log increase, P<0.001), and the combined endpoint of all-cause mortality and HF hospitalization (1.15 (1.08-1.22) per log increase, P<0.001). CONCLUSIONS: In patients with new-onset and worsening HF, higher plasma FGF23 levels were independently associated with volume overload, less successful uptitration of ACEi/ARBs and an increased risk of all-cause mortality and HF hospitalization.
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