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Ann Intern Med. 2010 May 18;152(10):640-8. doi: 10.7326/0003-4819-152-10-201005180-00004.

The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study.

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  • 1Division of Nephrologyand Hypertension, Department of Medicine, University of California-San Diego, CA 92161, USA.

Abstract

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.

DESIGN:

Observational study.

SETTING:

12 outpatient clinics in the San Francisco Bay area.

PATIENTS:

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

MEASUREMENTS:

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.

LIMITATION:

Participants had prevalent CAD.

CONCLUSION:

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

PRIMARY FUNDING SOURCE:

American Heart Association.

Comment in

PMID:
20479029
[PubMed - indexed for MEDLINE]
PMCID:
PMC3079370
Free PMC Article

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