The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study.
BACKGROUND
Fibroblast growth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A are regulators of mineral metabolism and inhibitors of vascular calcification. Whether circulating levels of each are associated with cardiovascular disease (CVD) events or mortality in populations without end-stage renal disease is unknown.


OBJECTIVE
To evaluate the associations of FGF23, ucMGP, and fetuin-A with mortality and CVD events.


METHODS
Observational study.


METHODS
12 outpatient clinics in the San Francisco Bay area.


METHODS
833 outpatients with stable coronary artery disease (CAD), recruited from 11 September 2000 to 20 December 2002.


METHODS
Fibroblast growth factor 23, ucMGP, and fetuin-A concentrations were measured at baseline. Participants were followed until 1 December 2008 for mortality and CVD events.


RESULTS
During a median follow-up of 6.0 years, 220 participants died and 182 had CVD events. Compared with participants with FGF-23 levels in the lowest tertile, those in the highest tertile had 2-fold greater risk for mortality (hazard ratio [HR], 2.15 [95% CI, 1.43 to 3.24]) and CVD events (HR, 1.83 [CI, 1.15 to 2.91]) after adjustment for traditional CVD risk factors, C-reactive protein levels, and kidney function. The highest ucMGP tertile was associated with lower mortality risk (HR, 0.48 [CI, 0.31 to 0.75]) and showed a nonsignificant trend toward lower CVD event risk by tertile analysis (HR, 0.65 [CI, 0.40 to 1.05])-an association that was significant when modeled continuously (P = 0.029). No significant association of fetuin-A with mortality (HR, 0.84 [CI, 0.55 to 1.27]) or CVD events (HR, 0.99 [CI, 0.64 to 1.55]) was observed.


CONCLUSIONS
Participants had prevalent CAD.


CONCLUSIONS
In outpatients with stable CAD, higher FGF23 and lower ucMGP levels are independently associated with mortality and CVD events.


BACKGROUND
American Heart Association.
Parker
Benjamin D
BD
Division of Nephrologyand Hypertension, Department of Medicine, University of California-San Diego, CA 92161, USA.
Schurgers
Leon J
LJ
Brandenburg
Vincent M
VM
Christenson
Robert H
RH
Vermeer
Cees
C
Ketteler
Markus
M
Shlipak
Michael G
MG
Whooley
Mary A
MA
Ix
Joachim H
JH
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein
D015415:Biomarkers; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein; C556354:AHSG protein, human; C000717427:FGF23 protein, human