Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

• Published in: Journal of the American Society of Nephrology Vol. 25; no. 2; pp. 349 - 360
• Main Authors: SCIALLA, Julia J, HUILIANG XIE, RAJ, Dominic S, WEI YANG, JIANG HE, LASH, James P, GO, Alan S, KUSEK, John W, FELDMAN, Harold, WOLF, Myles, RAHMAN, Mahboob, ANDERSON, Amanda Hyre, ISAKOVA, Tamara, OJO, Akinlolu, XIAOMING ZHANG, NESSEL, Lisa, HAMANO, Takayuki, GRUNWALD, Juan E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01-02-2014
• Subjects: Aged; Atherosclerosis - blood; Atherosclerosis - epidemiology; Biological and medical sciences; Biomarkers; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Clinical 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; Kidneys; Male; Medical sciences; Middle Aged; Models, Biological; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Renal failure; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - epidemiology; Risk; Risk Factors; Sensitivity and Specificity; Urinary system involvement in other diseases. Miscellaneous; Kidney disease; Nephrology; Urinary system disease; Fibroblast growth factor 23; Renal failure; Cardiovascular disease; Chronic kidney disease; Urology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2013050465

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.