Fibroblast Growth Factor-23 and Cardiovascular Disease in the General Population: The Multi-Ethnic Study of Atherosclerosis
Background—Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly stimulates left ventricular hypertrophy in experimental models. The role of FGF-23 in cardiovascular disease development in the general population is unclear. We tested associations of FGF-23 with major subclinical and clinical cardiovascular disease outcomes in a large prospective cohort.
Methods and Results—We evaluated 6,547 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We measured serum FGF-23 using the Kainos immunoassay. The MESA measured left ventricular (LV) mass by magnetic resonance imaging, coronary calcium (CAC) by computed tomography, and carotid intima-medial thickness (IMT) by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stoke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4 gram greater LV mass (95% CI 0.4, 4.5 greater) and a 26% greater odds of higher CAC scores (95% CI 9% to 46% greater) compared to the lowest quartile. Over 7.5 years follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% CI 3% to 37% greater) and a 14% greater risk of coronary heart disease (95% CI 1% to 28% greater). FGF-23 was not associated with carotid IMT or stroke.
Conclusions—Higher serum FGF-23 concentrations are associated with subclinical cardiac disease and with new heart failure and coronary disease events, but not with carotid IMT or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.
- fibroblast growth factor-23
- coronary artery calcium
- carotid intima-media thickness
- cardiovascular disease
- left ventricular mass
- heart failure
- left ventricular hypertrophy
- coronary heart disease
- Received November 13, 2013.
- Accepted March 17, 2014.