The Association of Fibroblast Growth Factor-23 with Cardiac Structure and Function in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Fibroblast growth factor-23 (FGF-23), a protein regulating phosphorus levels, is associated with the risk of heart failure, particularly in patients with chronic kidney disease (CKD), and with left ventricular (LV) hypertrophy in CKD. However, few studies have explored this association in the general population, and it is unknown whether FGF23 is associated with other parameters of cardiac structure and function. Methods: Among 5,533 Black or White participants attending Visit 5 (2011-2013) of the community-based ARIC study, we quantified the cross-sectional association of serum FGF-23 levels with echocardiographic measures of cardiac structure and function after accounting for potential confounders including kidney function. Results: Mean age was 76 [SD 5] years, 58 % were women, and 21 % were Black. Among the echocardiographic parameters tested ( Table ), higher FGF-23 levels were robustly associated with LV hypertrophy (adjusted odds ratio [aOR] 1.35 [95%CI 1.02-1.79] in top vs. bottom quartile), abnormal peak longitudinal strain (aOR 1.88 [1.32-2.69]), and left atrial enlargement based on left atrium volume index (aOR 1.34 [1.05-1.70]). No association was observed with E/e’ ratio. Higher FGF-23 was also associated with end-diastolic right ventricular (RV) enlargement (aOR 1.36 [1.04-1.78]). Similar results were observed when echocardiographic measures were modeled as continuous variables and when we stratified participants by demographics (age, sex, and race) or a history of cardiovascular disease. Conclusions: In community-dwelling older adults, in addition to LV hypertrophy, FGF-23 was associated with LV systolic and diastolic function as well as RV size, independent of kidney function and other potential confounders. These findings further support the involvement of FGF-23 in the pathophysiology of cardiac remodeling.