Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease

PLoS One. 2014 Apr 18;9(4):e95402. doi: 10.1371/journal.pone.0095402. eCollection 2014.


Objective: Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease.

Methods: Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6-12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed.

Results: Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48-0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04-1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31-0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62-1.71; p = 0.904).

Conclusions: Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Coronary Artery Disease / blood*
  • Female
  • Fibroblast Growth Factors / blood*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Vitamin D / blood*


  • Biomarkers
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23

Grant support

This work was supported by grants from the following: Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497, PI05/52475, PI05/1043, PS09/01405, and PI10/00072):; Spanish Society of Cardiology; Spanish Heart Foundation.; Spanish Society of Arteriosclerosis.; RECAVA (RD06/0014/0035);; Fundación Lilly.; Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101);; and AbbVie Laboratories. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.