TY - JOUR T1 - Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). JF - J Am Coll Cardiol Y1 - 2012 A1 - Ix, Joachim H A1 - Katz, Ronit A1 - Kestenbaum, Bryan R A1 - de Boer, Ian H A1 - Chonchol, Michel A1 - Mukamal, Kenneth J A1 - Rifkin, Dena A1 - Siscovick, David S A1 - Sarnak, Mark J A1 - Shlipak, Michael G KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Female KW - Fibroblast Growth Factors KW - Heart Failure KW - Humans KW - Kidney Function Tests KW - Male KW - Mortality KW - Renal Insufficiency, Chronic KW - United States AB -

OBJECTIVES: This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting.

BACKGROUND: FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown.

METHODS: Plasma FGF-23 was measured in 3,107 community-living persons ≥ 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status.

RESULTS: Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 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 FGF-23 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 FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95% CI: 1.32 to 2.83) for incident HF, and 1.49 (95% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95% CI: 1.05 to 1.59), 1.37 (95% CI: 0.99 to 1.89), and 1.07 (95% CI: 0.79 to 1.45).

CONCLUSIONS: FGF-23, 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.

VL - 60 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22703926?dopt=Abstract ER -