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.

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.