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

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

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Proteins / metabolism*
  • Calcium-Binding Proteins / blood*
  • Coronary Disease / blood*
  • Coronary Disease / mortality*
  • Extracellular Matrix Proteins / blood*
  • Female
  • Fibroblast Growth Factors / blood*
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • alpha-2-HS-Glycoprotein

Substances

  • AHSG protein, human
  • Biomarkers
  • Blood Proteins
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • alpha-2-HS-Glycoprotein
  • matrix Gla protein
  • Fibroblast Growth Factors
  • fibroblast growth factor 23