Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload - Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.

Abstract

Background: After the discovery of the Klotho gene, phosphate came into focus as a pathogenetic aging agent. Phosphate homeostasis is controlled by phosphate-regulating hormones: fibroblast growth factor 23 (FGF23), vitamin D₃, and parathyroid hormone. This study investigated the relationship between the deterioration in phosphate homeostasis and arterial stiffness by measuring serum FGF23 concentrations. Methods and Results: The study subjects comprised 82 hospitalized patients (31 males, 51 females; mean [±SD] age 78.6±10.5 years). All patients underwent chest computed tomography, measurement of central blood pressure (BP), and blood chemistry tests. Arterial calcification and/or stiffness was evaluated using the Agatston calcification score (ACS) and pulse wave velocity (PWV). PWV was significantly correlated with age (t=23.47, P<0.0001), estimated glomerular filtration rate (eGFR; t=-4.40, P<0.0001), and ACS (t=4.36, P<0.0001). Serum FGF23 concentrations were significantly correlated with age (t=2.52, P=0.014), eGFR (t=-3.37, P<0.001), serum inorganic phosphorus concentrations (t=3.49, P<0.001), serum vitamin D₃ concentrations (t=-4.57, P<0.001), ACS (t=2.30, P=0.025), augmentation pressure (t=2.48, P=0.015), central systolic BP (t=2.00, P=0.049), plasma B-type natriuretic peptide (BNP) concentrations (t=3.48, P<0.001), and PWV (t=2.99, P=0.004). PWV was positively related to augmentation pressure (t=4.09, P<0.001), central systolic BP (t=3.13, P=0.002), and plasma BNP concentrations (t=3.54, P<0.001). Conclusions: This study shows that the increase in serum FGF23 concentrations reflects deterioration of phosphate homeostasis and is an important predictor for arterial stiffness, which intensifies cardiac afterload.