Fibroblast growth factor 23 (FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study

Abstract

Background: Fibroblast growth factor 23 (FGF23) is an important regulatory hormone in phosphate and vitamin D metabolism. Here, we investigated the associations of FGF23 with traditional cardiovascular risk factors and with bone metabolism parameters as well as the impact of FGF23 upon long-term mortality in a large cohort of patients referred for coronary angiography.

Methods: We examined whether c-term FGF23 concentrations at baseline were associated with cardiovascular and total mortality in 2974 patients from the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). We investigated if these associations were independent from established cardiovascular risk factors as well as from other mineral regulating factors and bone biomarkers such as calcium, parathyroid hormone (PTH), alkaline phosphatase (AP), vitamin D, and serum phosphate.

Results: Mean age of participants was 63 ± 10 years; median c-term FGF23 serum levels were 54 (40-78) RU/ml. During a median follow-up of 9.9 years, 884 deaths (30%) occurred, 545 (18%) of which were cardiovascular. FGF23 significantly and inversely correlated with eGFR. AP, phosphate, and PTH increased in parallel with quartiles of FGF23. Age- and sex-adjusted hazard ratios (HRs) in the fourth quartile compared to the first quartile of FGF23 were 2.54 (95%CI, 2.09-3.09; p < 0.001) for all cause and 2.56 (95% CI, 1.99-3.28; p < 0.001) for cardiovascular mortality. These associations remained significant after additional adjustments for cardiovascular risk factors and bone biomarkers (calcium, PTH, AP, vitamin D, and phosphate): Adjusted HRs were 1.38 (95%CI, 1.26-1.52; p < 0.001) for all-cause and 1.35 (95%CI, 1.20-1.52; p < 0.001) for cardiovascular mortality for each increase by one standard deviation of c-term FGF23.

Conclusions: In patients undergoing coronary angiography baseline c-term FGF23 levels predict the risk for all-cause and cardiovascular mortality over 9.9 years of follow-up. These associations were independent of established cardiovascular risk factors and serum phosphate.

Keywords: Cardiovascular events; Coronary angiography; Coronary artery disease; Fibroblast growth factor 23, FGF23; Mortality; Outcome- phosphate.