Fibroblast Growth Factor-23 and Death, Heart Failure, and Cardiovascular Events in Community-Living Individuals

Abstract

Objective To determine the associations of FGF23 with death, HF, and CVD and investigate the influence of CKD in a general community-living population. Background FGF23 increases renal phosphorus excretion and inhibits vitamin D activation. In ESRD, high FGF23 levels are associated with mortality. The associations of FGF23 with death, heart failure (HF), and cardiovascular disease (CVD) in teh general population are unknown. Methods Plasma FGF23 was measured in 3,107 community-living persons ≥ 65 years in 1996–97, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status. Results Both lower eGFR and higher urine ACR were associated with high FGF23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (P interactions all < 0.006). In the CKD group (n=1,128), the highest FGF23 quartile had adjusted hazards ratios (HR) of 1.87 (1.47, 2.38) for all-cause death, 1.94 (1.32, 2.83) for incident HF, and 1.49 (1.02, 2.18) for incident CVD events compared to the lowest quartile. Corresponding HRs in those without CKD (n=1,979) were 1.29 (1.05, 1.59), 1.37 (0.99, 1.89), and 1.07 (0.79, 1.45). Conclusions FGF23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

“…Specific associations have been reported for incident hypertension, LVH, incident HF, higher coronary calcium scores, and incident coronary heart disease 17, 19, 27, 28. In this study we confirmed previous findings reported by Kestenbaum et al linking serum FGF‐23 to incident HF, and further studied the association with subtypes of HFpEF and HFrEF.…”

“…Fibroblast growth factor‐23 (FGF‐23), a hormone involved in phosphorus and vitamin D homeostasis,14, 15, 16 is linked to the development of HF and left ventricular hypertrophy (LVH) 17, 18. The administration of recombinant FGF‐23 promotes cardiomyocyte growth in animal models and higher circulating FGF‐23 concentrations are associated with HF and cardiovascular events in kidney disease and general populations 18.…”

Fibroblast Growth Factor-23 and the Long-Term Risk of Hospital-Associated AKI among Community-Dwelling Older Individuals

“…FGF-23 is a phosphaturic hormone that regulates mineral homeostasis (7,24). Recent studies have suggested that FGF-23 is associated with incident cardiovascular disease, left ventricular hypertrophy (LVH), heart failure, progression of kidney disease, and mortality (6,7,25).…”

“…Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone that is associated with increased risks of cardiovascular disease and progression to ESRD (6,7). Recent studies suggest that high circulating FGF-23 concentrations may also be due in part to tubular FGF-23 resistance, a state of tubular dysfunction that may also increase risk of AKI (8).…”

Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes

“…This finding is often observed at a stage of CKD where parathyroid hormone (PTH) and serum phosphorus concentrations remain normal. 7,8 This finding, coupled with the observation from prior studies that associations of FGF23 concentrations with adverse outcomes may be stronger in patients with CKD, [9][10][11][12] led us to hypothesize that high FGF23 concentrations may identify a novel dimension of kidney function that is not fully captured by estimated GFR (eGFR) or albuminuria. Specifically, we hypothesized that, independent of eGFR and albuminuria, FGF23 concentrations may be particularly high in individuals with kidney tubules that are less capable of responding to a high FGF23 stimulus.…”