03302nas a2200397 4500008004100000022001400041245015200055210006900207260001600276300001000292490000700302520213300309653000902442653002202451653001502473653001102488653003002499653001802529653001102547653002602558653000902584653001402593653003302607653001802640100001902658700001602677700002502693700002002718700002102738700002402759700001702783700002402800700002002824700002402844856003602868 2012 eng d a1558-359700aFibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study).0 aFibroblast growth factor23 and death heart failure and cardiovas c2012 Jul 17 a200-70 v603 a

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.

10aAged10aAged, 80 and over10aBiomarkers10aFemale10aFibroblast Growth Factors10aHeart Failure10aHumans10aKidney Function Tests10aMale10aMortality10aRenal Insufficiency, Chronic10aUnited States1 aIx, Joachim, H1 aKatz, Ronit1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aChonchol, Michel1 aMukamal, Kenneth, J1 aRifkin, Dena1 aSiscovick, David, S1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/1392