The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein with Mortality in Coronary Artery Disease

Higher levels of fibroglast growth factor 23 (FGF23) but lower levels of uncarboxylated matrix Gla protein (ucMGP), both regulators of mineral metabolism and inhibitors of vascular calcification, are associated with cardiovascular disease (CVD) events or death in outpatients who have stable coronary artery disease. A third protein, Fetuin-A, has no association.

It is known that abnormalities in mineral metabolism are associated with CVD risk in the general population. The three proteins at hand recently have been identified as regulators of arterial calcification but the relationship between these proteins and CVD events and mortality is unknown. This study recruited outpatients, with stable coronary artery disease, of San Francisco Bay area clinics between September 2000 and December 2002. The health of 833 participants was then tracked from their baseline examinations until December 2008.

Key Findings:

  • Participants in the top tertile of FGF23 levels had a three-fold greater risk of CVD events or mortality than those in the bottom tertile. After adjustment for factors such as kidney function, CVD risk factors and C-reactive protein, the top tertile still had a two-fold greater risk.
  • By comparison, participants in the highest tertile of ucMGP had a 50 percent lower risk of mortality, compared to those in the bottom tertile. This association remained the same after adjustment.
  • There was no relationship seen between levels of Fetuin-A and risk of death or CVD events.
  • These associations between FGF23 and ucMGP were not altered by the presence of kidney disease or diabetes, although higher ucMGP levels in persons without diabetes were associated with a reduced risk of death.

The mechanisms for how these proteins impact the risks of CVD events and mortality is an avenue for further investigation. However, these study results may help identify persons at greater risk of CVD events and death and ultimately lead to prevention and treatments.