Relationship of Fibroblast Growth Factor 23 With Hospitalization for Heart Failure and Cardiovascular Outcomes in Patients Undergoing Cardiac Surgery

Abstract

Background Fibroblast growth factor 23 (FGF‐23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF‐23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF‐23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF‐23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF‐23 modeled as a continuous variable (adjusted hazard ratio for a 1‐unit increase in standardized log‐transformed biomarker, 1.82 [95% CI, 1.34–2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF‐23 to N‐terminal pro‐B‐type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34–0.81]; P <0.001; integrated discrimination increment, 0.03 [95% CI, 0.01–0.05]; P <0.001). Conclusions FGF‐23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF‐23 evaluation may improve detection of high‐risk patients.

Roles of fibroblast growth factors in the treatment of diabetes

“…Fibroblast growth factors (FGFs), consisting of 23 family members (FGF-1-23) in humans[ 6 , 7 ], play important roles in metabolic homeostasis and cell biological processes since alteration of the expression of FGFs is implicated in many chronic diseases. These diseases include obesity[ 8 , 9 ], metabolic-associated fatty liver disease[ 10 - 13 ], diabetes[ 14 , 15 ], and diabetic complications such as hyperthyroidism[ 16 ], chronic kidney disease (CKD)[ 17 , 18 ], cardiovascular disease[ 19 , 20 ], and cancer[ 21 , 22 ]. Investigations have shown that FGFs can function as molecular targets for the treatment of diabetes and diabetes-associated metabolic disorders.…”