Fibroblast Growth Factor 23 and Risk of New Onset Heart Failure With Preserved or Reduced Ejection Fraction: The PREVEND Study

Abstract

Background The role of fibroblast growth factor 23 (FGF23) in the development of new‐onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C‐terminal FGF23 with development of new‐onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population‐based cohort. Methods and Results We studied 6830 participants (aged 53.8±12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1±15.7 mL/min per 1.73 m 2 ) in the community‐based PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study who were free of HF at baseline. Cross‐sectional multivariable linear regression analysis showed that ferritin (standardized β, −0.24; P <0.001) and estimated glomerular filtration rate (standardized β, −0.13; P <0.001) were the strongest independent correlates of FGF23. Multivariable Cox proportional hazard regression was used to study the association between baseline FGF23 and incident HF, HFrEF (ejection fraction ≤40%) or HFpEF (ejection fraction ≥50%). After median follow‐up of 7.4 [IQR 6.9–7.9] years, 227 individuals (3.3%) developed new‐onset HF, of whom 132 had HFrEF and 88 had HFpEF. A higher FGF23 level was associated with an increased risk of incident HF (fully adjusted hazard ratio, 1.29 [95% CI, 1.06–1.57]) and with an increased risk of incident HFrEF (fully adjusted hazard ratio, 1.31 [95% CI, 1.01–1.69]). The association between FGF23 and incident HFpEF lost statistical significance after multivariable adjustment (hazard ratio, 1.22 [95% CI, 0.87–1.71]). Conclusions Higher FGF23 is independently associated with new‐onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment.