Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: a systematic review and meta-analysis

Background: and Objective: Growth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) were considered as predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations of GDF-15 and FGF-23 with the risk of atrial fibrillation (AF). Methods: : An electronic search was conducted in Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in PROSPERO database (CRD42020182226). Results: : In total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 was elevated in patients with AF. Analysis of categorical variables showed a higher serum FGF-23 level was associated with increased risk of AF (relative risk (RR)=1.28, 95% confidence interval (CI): 1.05-1.56), but not GDF-15 (RR=0.91, 95% CI: 0.20-4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 level and the risk of AF (P nonlinear = 0.9507), with a RR elevation by 7% for every 20 pg/ml increase in the serum FGF-23 level (95% CI: 1.02–1.13). No remarkable linkage was found between serum GDF-15 level and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 level and AF was 1.01 (95% CI: 0.998–1.02). Conclusion: Our study showed a positive linear correlation of serum FGF-23 level with the risk of AF. However, no significant association was found between GDF-15 and risk of AF. Further studies are warranted to clarify whether serum FGF-23 level may be significant to predict the risk of AF.