title: Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease.
abstract: Disturbances in phosphate homeostasis are common in patients with chronic kidney disease. As kidney function declines, circulating concentrations of phosphate and the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise progressively. Higher serum levels of phosphate and FGF-23 are associated with an increased risk of adverse outcomes, including all-cause mortality and cardiovascular events. The associations between higher FGF-23 levels and adverse cardiovascular outcomes are generally independent of serum phosphate levels, and might be strongest for congestive heart failure. Higher serum phosphate levels are also modestly associated with an increased risk of cardiovascular events even after accounting for FGF-23 levels. This observation suggests that FGF-23 and phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed, animal models implicate high serum phosphate as a mechanism of vascular calcification and endothelial dysfunction, whereas high levels of FGF-23 are implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart suggest that future population-level and individual-level interventions will need to simultaneously target these molecules to reduce the risk of associated cardiovascular events.
authors.affiliation: University of Miami Miller School of Medicine, University of Miami, 1120 North West 14th Street, Suite 815, Miami, FL 33136, USA.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Scialla
authors.affiliation: Feinberg School of Medicine, Northwestern University, 633 North St Clair Street, Suite 18-089, Chicago, IL 60611, USA.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D004044:Dietary Proteins / Q000008:administration & dosage; D042783:Endothelial Cells / Q000187:drug effects; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism*; D061205:Vascular Calcification / Q000139:chemically induced
chemical_list: D004044:Dietary Proteins; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins