Fibroblast growth factor-23 and cardiovascular events in CKD

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...

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Published in:Journal of the American Society of Nephrology Vol. 25; no. 2; p. 349
Main Authors: Scialla, Julia J, Xie, Huiliang, Rahman, Mahboob, Anderson, Amanda Hyre, Isakova, Tamara, Ojo, Akinlolu, Zhang, Xiaoming, Nessel, Lisa, Hamano, Takayuki, Grunwald, Juan E, Raj, Dominic S, Yang, Wei, He, Jiang, Lash, James P, Go, Alan S, Kusek, John W, Feldman, Harold, Wolf, Myles
Format: Journal Article
Language:English
Published: United States 01.02.2014
Subjects:
Aged
Atherosclerosis - blood
Atherosclerosis - epidemiology
Biomarkers
Cardiovascular Diseases - blood
Cardiovascular Diseases - epidemiology
Comorbidity
Female
Fibroblast Growth Factors - blood
Follow-Up Studies
Heart Failure - blood
Heart Failure - epidemiology
Hospitalization - statistics & numerical data
Humans
Incidence
Kidney Failure, Chronic - epidemiology
Kidney Failure, Chronic - etiology
Male
Middle Aged
Models, Biological
Renal Insufficiency, Chronic - blood
Renal Insufficiency, Chronic - epidemiology
Risk
Risk Factors
Sensitivity and Specificity
ISSN:1533-3450, 1533-3450
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Summary: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.
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ISSN:1533-3450
1533-3450
DOI:10.1681/ASN.2013050465