Fibroblast growth factor 23 mediates the association between iron deficiency and mortality in worsening heart failure

摘要

Iron deficiency (ID) is prevalent in heart failure (HF) and associated with a poor prognosis. , The pathophysiological mechanisms of ID are not fully understood. While a strong link between ID and anaemia exists, ID is associated with increased mortality in non‐anaemic patients as well. Additionally, intravenous iron administration is also beneficial in non‐anaemic patients. This implies other, non‐haematopoietic effects of ID on outcome. ID has been linked to increased levels of fibroblast growth factor 23 (FGF23), which is a phosphaturic osteocyte‐derived hormone. FGF23 inhibits renal phosphate reabsorption and regulates 1,25(OH) vitamin D. The association between iron status and FGF23 originates from studies in FGF23‐related autosomal dominant hypophosphataemic rickets, which has an iron‐dependent onset. Previously, we have shown that in HF patients, FGF23 is independently associated with congestion, unsuccessful angiotensin‐converting enzyme inhibitor and angiotensin receptor blocker up‐titration, and poor prognosis. Moreover, FGF23 has been linked to incident HF and mortality in community‐based studies and development of left ventricular hypertrophy and mortality in chronic kidney disease patients. , Recent preclinical data suggest an association between FGF23 and cardiac renin–angiotensin–aldosterone system activation, thereby leading to cardiac fibrosis and hypertrophy. Finally, correction of ID seems related to significant reductions in FGF23 levels in HF patients, a finding which further links iron status and FGF23 together. The association between iron status, FGF23 and outcome in HF is currently unclear. This study therefore focused on the interplay between iron and FGF23, and whether FGF23 mediates the association between iron status and outcome in HF.