Background: Fibroblast growth factor-23 (FGF-23) is a phosphaturic factor previously associated with left ventricular hypertrophy and systolic dysfunction among individuals with chronic kidney disease. Whether FGF-23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain. We investigated associations of FGF-23 with cardiac structural abnormalities among individuals with a broad range of kidney function and explored potential biological mechanisms using cardiac magnetic resonance imaging and histology in klotho-null mice, an established model of constitutively elevated FGF-23.
Methods and results: Among 887 participants with coronary artery disease in the Heart and Soul Study, FGF-23 was modestly associated with worse left ventricular ejection fraction (-1.0% per standard deviation increase in lnFGF-23; standard error, 0.4%), but was not associated with the overall prevalence of concentric hypertrophy (odds ratio, 1.5; CI, 0.9 to 2.4) or eccentric hypertrophy (odds ratio, 1.1; CI, 0.9 to 1.3). FGF-23 was only associated with concentric hypertrophy among individuals with diminished kidney function (eGFR <60 mL/min per 1.73 m(2); odds ratio, 2.3; CI, 1.0 to 5.3; P-interaction=0.28). Comparing klotho-null with wild-type mice, null mice did not have greater left ventricular mass (P=0.37) or a lower ejection fraction (P=0.94).
Conclusions: Together, our results suggest that FGF-23 is unlikely to have major effects on cardiovascular structure and function among patients free of substantial chronic kidney disease, and these effects may not be independent of the klotho coreceptor.
Keywords: chronic kidney disease; hypertrophy; structure.