The phosphatonin fibroblast growth factor 23 links calcium-phosphate metabolism with left-ventricular dysfunction and atrial fibrillation

Eur Heart J. 2011 Nov;32(21):2688-96. doi: 10.1093/eurheartj/ehr215. Epub 2011 Jul 6.

Abstract

Aims: High serum phosphate is linked to cardiovascular morbidity and mortality in the general population. Fibroblast growth factor 23 (FGF-23) is a critical phosphate regulating hormone, potentially reflecting phosphate load better than a single serum phosphate measurement. Recent pioneering echocardiographic studies associated FGF-23 with left-ventricular morphology. However, the association between FGF-23 and left-ventricular function is unknown, prompting us to investigate this relationship in our HOM SWEET HOMe study.

Methods and results: We studied the association between C-terminal FGF-23, coronary artery disease, and left-ventricular function in 885 subjects undergoing elective coronary angiography. Left-ventricular function was assessed with ventriculography. More, pro-brain natriuretic peptide (pro-BNP) plasma levels were measured. The presence of left-ventricular hypertrophy and atrial fibrillation was assessed by electrocardiography. Patients with an ejection fraction <40% had significantly higher FGF-23 levels compared with patients with the ejection fraction >40% (P< 0.001). In multivariable regression analysis, the observed relationship between FGF-23 and left-ventricular function remained significant after adjustment for estimated glomerular filtration rate, presence of left-ventricular hypertrophy, and other confounding variables. In accordance, FGF-23 significantly correlated with pro-BNP plasma levels (r = 0.31; P< 0.001). Prevalent atrial fibrillation was associated with elevated FGF-23 levels, while the presence of coronary artery disease was not.

Conclusions: Fibroblast growth factor 23 levels are associated with left-ventricular function and atrial fibrillation even in the absence of renal function impairment. Of note, these cross-sectional data cannot prove causality; therefore, future studies will have to discern whether FGF-23 exerts a direct untoward effect on the myocardium, or rather represents an 'innocent bystander' which reflects a high phosphate burden.

MeSH terms

  • Atrial Fibrillation / blood
  • Atrial Fibrillation / etiology*
  • Biomarkers / metabolism
  • Calcium Phosphates / metabolism*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / etiology*
  • Cross-Sectional Studies
  • Electrocardiography
  • Fibroblast Growth Factors / metabolism*
  • Glomerular Filtration Rate / physiology
  • Humans
  • Hypertrophy, Left Ventricular / blood
  • Hypertrophy, Left Ventricular / etiology
  • Kidney Diseases / complications
  • Kidney Diseases / physiopathology
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / etiology*

Substances

  • Biomarkers
  • Calcium Phosphates
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • calcium phosphate