Iron Deficiency Defined as Depleted Iron Stores

Study Questions:

Is iron deficiency (ID), defined as depleted iron stores accompanied by unmet by cellular iron requirements, a predictor of poor outcomes in acute heart failure (AHF)?


The study cohort was comprised 165 AHF patients (ages 65 ± 12 years, 81% men, 31% de novo HF). To diagnose ID, the study investigators prospectively applied low serum hepcidin reflecting depleted iron stores (<14.5 ng/ml, the fifth percentile in healthy peers) and high-serum soluble transferrin receptor (sTfR) reflecting unmet cellular iron requirements (≥1.59 mg/L, the 95th percentile in healthy peers).


The authors found that concomitance of low hepcidin and high sTfR (the most profound ID) in 37%, isolated either high sTfR or low hepcidin was found in 29% and 9% of patients, and 25% of subjects demonstrated preserved iron status. Patients with the most profound ID had peripheral edema, high N-terminal-proB-type natriuretic peptide, high uric acid, low hemoglobin (p < 0.05), and 5% in-hospital mortality (0% in remaining patients); 20% (n = 33) of patients died during the 12-month follow-up. Also, those with most profound ID had the highest 12-month mortality ([41%; 95% confidence interval, 29-53%]when compared with those with isolated high sTfR [15%; 5-25%], isolated low hepcidin [7%; 0-19%], and preserved iron status [0%]; p < 0.001). The investigators also saw analogous mortality patterns separately in anemic and nonanemic patients.


The authors concluded that iron deficiency, defined as depleted body iron stores and unmet cellular iron requirements, is common in AHF, and that it is associated with the poor outcome.


This is an important study because it demonstrates that depletion of micronutrients such as iron is associated with increased mortality in patients with AHF, whereas those with preserved iron status had a better outcome. This study should result in further investigation to determine the mechanisms underlying profound iron deficiency and whether indeed simply replacing iron will improve outcomes.

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