Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies

Abstract Background and aims The prognostic value of fibroblast growth factor 23 (FGF23) for mortality remains controversial. We performed a meta-analysis of cohort studies to examine the controversial relationship between FGF23 and mortality. Methods PubMed, EMBASE, the Cochrane Library databases and reference bibliographies were searched through September 2016 to identify prospective cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for FGF23 and mortality. A random effects model was used to pool the risk estimates. A dose-response analysis of the risk for all-cause mortality associated with FGF23 was conducted using the generalized least squares trend estimation method. Results Nineteen prospective cohort studies were eligible for inclusion in this meta-analysis, of which 16 reported all-cause mortality and 9 reported cardiovascular mortality. During the follow-up periods ranging from 1 to 18.6 years, 5606 deaths occurred among 22,805 participants and 2458 cardiovascular deaths occurred among 28,845 participants. Elevated FGF23 was associated with an increased risk of all-cause mortality (RR 1.68; 95% CI 1.48–1.92) and cardiovascular mortality (RR 1.68; 95% CI 1.38–2.04) with moderate heterogeneity. These associations were not markedly modified by the geographic location, follow-up length, patient predisposition, FGF23 measurement or study quality. A sensitivity analysis yielded a similar effect on the pooled risk estimate. Evidence of a nonlinear relationship between FGF23 and all-cause mortality was observed in the dose-response analysis, with the risk gradually increasing as FGF23 increased. Conclusions This meta-analysis showed that individuals with increased plasma FGF23 levels might suffer a higher risk of all-cause mortality and cardiovascular mortality.