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

Abstract

Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321. 2. Iraqi W, Rossignol P, Angioi M, Fay R, Nuee J, Ketelslegers JM, Vincent J, Pitt B, Zannad F. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

Eplerenone prevents an increase in serum carboxy‐terminal propeptide of procollagen type I after myocardial infarction complicated by left ventricular dysfunction and/or heart failure

“…4 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. 5 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. 6,7 Recent preclinical data suggest an association between FGF23 and cardiac renin-angiotensin-aldosterone system activation, thereby leading to cardiac fibrosis and hypertrophy.…”

“…This study is a post-hoc analysis of the 'systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure' (BIOSTAT-CHF), which has been described previously. 5 In short, BIOSTAT-CHF prospectively enrolled 2516 patients with worsening signs and/or symptoms of HF and a left ventricular ejection fraction ≤40% or brain natriuretic peptide levels >400 pg/mL or N-terminal prohormone of brain natriuretic peptide >2000 pg/mL. BIOSTAT-CHF was approved by local medical ethics committees at each participating centre.…”

“…We measured the following biomarkers in 2279 stored samples, drawn at the time of presentation at the emergency department or hospital admission: iron, transferrin saturation (TSAT), ferritin, hepcidin, soluble transferrin receptor (sTfR) and FGF23 [using a c-terminal ELISA (Immutopics, Inc., San Clemente, CA, USA), measuring both intact and c-terminal FGF23 cumulatively]. 5 Univariable and multivariable linear regression analyses were performed using log-transformed FGF23 levels as dependent variables and log-transformed TSAT, sTfR, ferritin and hepcidin as independent variables. The multivariable models were adjusted for predictors that have previously been associated with FGF23.…”

“…The multivariable models were adjusted for predictors that have previously been associated with FGF23. 5 Univariable and FGF23-adjusted restricted cubic splines based on Cox proportional hazard regression were constructed to assess the association between iron parameters and all-cause mortality. Mediation analyses were performed according to the methods described by Baron and Kenny.…”

“…It should be noted that for this substudy, PICP measurements were performed in samples that were stored for more than 15 years. Although PINP was stable over a duration of 12 months at −80 ∘ C, 5 data on long-term storage and stability of PICP are lacking. The possibility of degradation of PICP in time and/or skewness of the results cannot therefore be excluded.…”