FGF-23 and Long-term Outcome in Peripheral Artery Disease

Atherosclerotic peripheral artery disease (PAD) and chronic kidney disease (CKD) are highly interconnected diseases, while causes for excess mortality are not well-defined. Fibroblast growth-factor 23 (FGF-23) is elevated in mineral bone disease of CKD and was shown to be associated with higher mortality. However, it is not known if this association extends to PAD. FGF-23 was measured by ELISA in serum samples of 298 patients with stable PAD (Fontaine stage I-II) with an estimated glomerular filtration rate (eGFR) of 72 (58-85) ml/min. Mortality was assessed after a long-term follow-up of up to 10 years. FGF-23 showed significant associations with markers of metabolic syndrome (triglycerides <i>r</i> = .25, <i>P</i> < .001, high-density lipoprotein cholesterol (HDL-C) r = -.28, <i>P</i> < .001, c-reactive protein (CRP) <i>r</i> = .14, <i>P</i> = .016). Multivariable Cox-regression outcome analyses showed significant associations between FGF-23 and all-cause mortality (hazard ratio 1.35, 95% confidence interval 1.05-1.74) in PAD patients even after adjustment for traditional cardiovascular risk factors and renal excretory function. FGF-23 is associated with higher mortality in patients with PAD. Our findings indicate that FGF-23 has detrimental effects on patients with PAD that are independent of renal excretory function.