Fibroblast growth factor-23 and cardiovascular disease in the general population: the Multi-Ethnic Study of Atherosclerosis

Abstract

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 6547 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 mass by MRI, coronary calcium by computed tomography, and carotid intima-media thickness by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stroke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g greater left ventricular mass (95% confidence interval, 0.4-4.5 greater) and a 26% greater odds of higher coronary calcium scores (95% confidence interval, 9%-46% greater) compared with the lowest quartile. During 7.5-year follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% confidence interval, 3%-37% greater) and a 14% greater risk of coronary heart disease (95% confidence interval, 1%-28% greater). FGF-23 was not associated with carotid intima-media thickness 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 intima-media thickness or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.

Keywords: cardiovascular diseases; carotid intima-media thickness; coronary disease; fibroblast growth factor 23; heart failure; hypertrophy, left ventricular; stroke.

© 2014 American Heart Association, Inc.

Figures

Figure 1. Cumulative incidences of cardiovascular events by serum FGF-23 concentration

Y-axis depicts the unadjusted cumulative incidences of heart failure, coronary heart disease, and stroke, respectively; X-axis depicts follow-up time in the study with interval censoring. Data are presented by quartiles of serum FGF-23 concentration with the number at risk and cumulative number of events by year described below the X-axis.

Figure 2. Associations of serum FGF-23 concentration with incident heart failure and coronary heart disease events by subgroup

Forest plot depicting associations of 20-pg/mL greater serum FGF-23 concentrations with incident heart failure and incident coronary heart disease events by subgroup. The X-axis represents the relative risk (closed circles) and 95% confidence interval (horizontal lines) for each association. The vertical hashed lines represent hazards ratio for the full cohort and the light grey vertical lines represent a hazard ratio of 1.0.