Fibroblast growth factor-23 and incident atrial fibrillation: The multi-ethnic study of atherosclerosis (MESA) and the cardiovascular health study (CHS)

Jehu S. Mathew, Michael C. Sachs, Ronit Katz, Kristen K. Patton, Susan R. Heckbert, Andrew N. Hoofnagle, Alvaro Alonso, Michel Chonchol, Rajat Deo, Joachim H. Ix, David S. Siscovick, Bryan Kestenbaum, Ian H. De Boer

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Abstract

BACKGROUND - : Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction. METHODS AND RESULTS - : We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23. CONCLUSION - : Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.

Original languageEnglish (US)
Pages (from-to)298-307
Number of pages10
JournalCirculation
Volume130
Issue number4
DOIs
StatePublished - Jul 22 2014

Keywords

  • atrial fibrillation
  • chronic
  • fibroblast growth factors
  • minerals
  • renal insufficiency

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    Mathew, J. S., Sachs, M. C., Katz, R., Patton, K. K., Heckbert, S. R., Hoofnagle, A. N., Alonso, A., Chonchol, M., Deo, R., Ix, J. H., Siscovick, D. S., Kestenbaum, B., & De Boer, I. H. (2014). Fibroblast growth factor-23 and incident atrial fibrillation: The multi-ethnic study of atherosclerosis (MESA) and the cardiovascular health study (CHS). Circulation, 130(4), 298-307. https://doi.org/10.1161/CIRCULATIONAHA.113.005499