title: Fibroblast growth factor-23 and cardiovascular events in CKD.
abstract: An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44±15 ml/min per 1.73 m(2)). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to 1.40]; HR for highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida;
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Scialla
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xie
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
authors.forename: Amanda Hyre
authors.initials: AH
authors.lastname: Anderson
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Akinlolu
authors.initials: A
authors.lastname: Ojo
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.forename: Juan E
authors.initials: JE
authors.lastname: Grunwald
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Raj
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: James P
authors.initials: JP
authors.lastname: Lash
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.forename: Harold
authors.initials: H
authors.lastname: Feldman
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology; D012306:Risk; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23