Fibroblast Growth Factor-23 and Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS)
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 associations of circulating FGF-23 concentration with incident AF among 6,398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1,350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over 7.7 and 8.0 years median follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each two-fold higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (HR 1.41 [95% CI 1.13-1.76], p=0.003) and a 30% higher risk of incident AF in CHS (HR 1.30 [95% CI 1.05-1.61], p=0.016), adjusting for potential confounding characteristics including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (HR 1.15 per 0.5 mg/dL [CI 1.02-1.31], p-value=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjusting for FGF-23.
Conclusions—Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
- Received August 8, 2013.
- Revision received April 25, 2014.
- Accepted May 6, 2014.