The association of fibroblast growth factor 23 at mid-life and late-life with subsequent risk of cardiovascular disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Fibroblast growth factor 23 (FGF-23) regulates phosphorus and is associated with cardiovascular disease (CVD), particularly in patients with chronic kidney disease. However, data are limited regarding its contribution to different CVD subtypes across wide age ranges in the general population. Methods: Using data from ARIC, we evaluated the associations of FGF-23 with heart failure (HF), coronary heart disease (CHD), stroke, and composite CVD (any CVD event) in 12,039 participants at mid-life (visit 3 [1993–1995], mean age 60.0 [SD 5.7] years) and 5608 of the same participants at late-life (visit 5 [2011−2013], 75.5 [5.1] years). Results: During a median of 9.0 years from visit 3 and 6.9 years from visit 5, we observed 1636 and 1137 composite CVD events, respectively. Higher FGF-23 at visit 5, but not necessarily at visit 3, was significantly associated with the risk of CVD independently of potential confounders including kidney function (adjusted HRs for top vs. bottom quartile, 1.56 [95% CI, 1.30–1.87] at visit 5 and 1.10 [95% CI, 0.95–1.27] at visit 3, p-for-difference < 0.001). We observed similar patterns in key demographic and clinical subgroups without interactions. Among CVD subtypes, HF was the only subtype robustly associated with higher FGF-23 at both visits. Conclusion: Higher FGF-23 concentrations at late-life but not necessarily at mid-life were independently associated with the risk of CVD. Among CVD subtypes tested, only HF showed robust associations with FGF-23 at both mid-life and late-life.