Clinical significance of serum fibroblast growth factor 23 as a surrogate marker of the cardiorenal hemodynamic state in patients with heart failure

Abstract

Purpose: Although the direct hemodynamic mechanism was contributed to the occurrence of cardiorenal syndrome, the surrogate marker for the detection for the abnormalities of cardiorenal hemodynamic state in early stage, has not been established. Fibroblast growth factor 23 (FGF23), one of phosphate-regulating hormones, is known to be linked to renal function and predictive factor of the mortality in patients with chronic kidney disease, whereas less is known in patients with heart failure (HF). We aimed to determine the relation between serum FGF23 levels and hemodynamic state, cardiac function in patients with HF and relatively preserved renal function. Methods: We investigated 867 subjects (726 persons from a community population without overt heart and renal diseases), and prospectively enrolled 141 consecutive hospitalized HF patients with more than 40 ml/min/1.73 m2 of estimated glomerular filtration rate (eGFR). We further prospectively studied 117 patients with RHC and 50 patients with histological examination using right ventricle (RV) biopsy. The clinical outcome was defined as the occurrence of either cardiovascular death or re-hospitalization for HF, during 180 days after the entry to this study. This study was approved by our institutional review board and was conducted in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Results: The median FGF23 level of the patients with HF was significantly higher than that of healthy population who were matched with gender and eGFR of HF population (39.1 [25th to 75th interquartile range: 31.3-51.9] v.s. 28.3 [22.7-37.4] pg/ml, respectively, p<0.001). RHC revealed that serum FGF23 levels have the inverse correlation with cardiac index (r=-0.31, p<0.001), mixed venous oxygen saturation (r=-0.41, p<0.001) and the positive correlation with right atrial pressure (r=0.25, p=0.006). Histological analysis revealed that the fibrosis area in RV was significantly larger in High FGF23 group (≥39.1 pg/ml) than that in Low FGF23 group (<39.1 pg/ml). Importantly, the frequency of cardiac event was significantly higher in High FGF23 group than Low FGF23 group (p=0.03). Conclusions: The serum FGF23 level was elevated in patients with heart failure and no overt renal diseases, with a significant correlation with both cardiac output and venous congestion relating renal perfusion pressure, and clinical outcome. FGF23 could be a novel surrogate marker for cardiorenal hemodynamic state, suggesting to be accompanied with important pathophysiological roles in the process of deteriorating heart failure.