Fibroblast growth factor-23 is an independent predictor of hospitalization for heart failure and major cardiovascular adverse events in patients undergoing cardiac surgery

Abstract

Abstract Background Fibroblast growth factor 23 (FGF-23) plays a crucial role in regulating phosphate and vitamin D metabolism and was proved to be associated with an increased risk for fatal events in individuals suffering from cardiovascular diseases. Since data on the prognostic potential of FGF-23 in individuals undergoing cardiac valve and/or coronary artery bypass graft (CABG) surgery are scarce, the specific objective of this study was to investigate the impact of FGF-23 on postoperative complications, particularly postoperative atrial fibrillation (POAF), hospitalization for heart failure (HHF) and cardiovascular (CV) death in an unselected patient population after cardiac surgery. Methods Within the present investigation, patients undergoing elective cardiac valve and/or CABG surgery were prospectively enrolled at the Department of Cardiac Surgery of a medical university. Blood samples were taken prior to surgery and FGF-23 concentrations were subsequently assessed. Patients were followed prospectively until the primary study endpoint (CV death) was reached. Results In total, 462 patients were included in the present analysis and followed over a median of 3.9 years. During follow-up 67 (14.5%) patients died. The patients' median age was 70 years (interquartile range [IQR] 60 to 75) and 133 (28.8%) were female. The median FGF-23 level in the entire study population was 1.9 pmol/L (IQR 1.2 to 3.5). Notably, individuals with POAF showed significantly higher FGF-23 levels than patients without (p<0.001). After stratification into tertiles (T) of FGF-23 patients in the highest FGF-23 tertile showed greater rates of HHF, all-cause and CV death. Furthermore, FGF-23 was consistently associated with POAF development showing an adjusted OR for a 1-unit increase in standardized log-transformed biomarker of 1.28 (95% CI: 1.01 to 1.63), along with an adjusted OR of 2.04 (95% CI 1.33 to 3.13, p=0.001) for the pre-defined high risk cut-off value. A steady risk increase for HHF and CV death among ascending FGF-23 tertiles has been noted. Moreover FGF-23 showed strong discriminatory performance (area under the curve [AUC] 0.69, 95% CI 0.61–0.77). Reclassification analysis indicated that the addition of FGF-23 to NT-proBNP provides a significant improvement in risk discrimination (NRI at the event rate: 0.58, 95% CI 0.34–0.81, p-value <0.001; IDI: 0.03, 95% CI 0.01–0.05, p-value= 0.001). Conclusion FGF-23 proved to be a strong and independent predictor for POAF, HHF and CV death in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of patients at risk, who require in-depth clinical attention throughout the peri- and postoperative phase after cardiac surgery. Funding Acknowledgement Type of funding sources: None.