Different definitions of iron deficiency appear to impact prognosis in chronic HF
Different definitions of iron deficiency provide discordant results for prevalence and prognosis of chronic HF, according to research published in the Journal of the American College of Cardiology.
The researchers found definitions for iron deficiency that are lacking specificity may attenuate the benefits of IV iron observed in trials, whereas definitions lacking sensitivity may exclude patients who should receive IV iron.
“Getting the definition of iron deficiency right is important for clinical trials and clinical practice,” Gabriele Masini, MD, of the department of medical and surgical specialties at the University of Brescia, Italy, and colleagues wrote. “We found that iron deficiency is common among ambulatory patients with HF, but the prognostic implications differ according to definition.”
Masini and colleagues analyzed data from 4,422 patients with HF referred to a regional clinic from 2001 to 2019 (median age, 75 years; 60% men; 32% with reduced left ventricular ejection fraction). Serum ferritin, transferrin saturation and serum iron were used as biomarkers of iron deficiency. Researchers followed patients through June 2019.
Prevalence varied by definition
The prevalence of iron deficiency ranged from 44% to 68%, depending on the definition. Among patients who met guideline criteria for iron deficiency, 83% had a ferritin level less than 100 ng/mL, whereas 32% had a transferrin saturation of 20% of greater and a serum iron greater than 13 µmol/L. Among those who did not have iron deficiency according to guideline criteria, 20% had a transferrin saturation less than 20% or a serum iron of 13 µmol/L or less.
“Many patients fulfilled one definition of iron deficiency but not others,” the researchers wrote.
Irrespective of definition, iron deficiency was more common among women and those with more severe symptoms, anemia or preserved EF. A transferrin saturation greater than 20% and serum iron greater 13 µmol/L — but not guideline criteria — were associated with higher 5-year mortality (HR = 1.27; 95% CI, 1.14-1.43; P < .001; and HR = 1.37; 95% CI, 1.22-1.54; P < .001, respectively).
There was a trend toward serum ferritin of less than 100 ng/mL being associated with lower mortality, with an HR of 0.91 (95% CI, 0.81-1.01; P = .09).
Lower serum ferritin, better survival
“We did not find any association between the current guideline definition of iron deficiency and mortality; indeed, lower serum ferritin concentrations were associated with a better survival,” the researchers wrote. “Among other definitions of iron deficiency, serum iron less than 13 µmol/L were independently associated with death, with no interaction between HF phenotypes.”
The researchers noted that about two-thirds of patients fulfilled the guideline definition of iron deficiency; however, about one-third of those meeting the guideline definition had a transferrin saturation greater than 20%.
“If this latter group of patients does not truly have iron deficiency but is being included in trials of IV iron, this could attenuate any observed benefit and might even lead to a neutral result,” the researchers wrote.
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