Letter regarding the article 'Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure'.

Abstract

Recently, we read with great interest the study by Graham et al. about iron deficiency (ID) and anaemia in chronic heart failure patients.1 In their report, the authors evaluate the prevalence and incidence of ID and anaemia and their association with mortality in chronic heart failure patients. They found that 10% had anaemia without iron deficiency, 23% had ID without anaemia, 20% had both, and 47% had neither. Mortality was higher in those with persistent or incident ID at 1 year in multivariable models, but resolution of ID was associated with a lower mortality. Additionally, anaemia was associated with a poor outcome even if it resolved. They concluded that the prevalence and incidence of ID and anaemia were high in chronic heart failure, and persistent or incident ID (defined by a serum iron ≤13 µmol/L) was associated with higher mortality and resolution of ID with lower mortality. Although the results were attractive, some points should be noticed. As acknowledged by the authors, the definition of ID based on serum ferritin or transferrin saturation might erroneously estimate the prevalence of ID in chronic heart failure patients. As an acute-phase protein, serum ferritin can be affected by multiple confounding factors, such as inflammation, infection, oxidative stress, liver disease, renal failure and autoimmune diseases.2 These disorders or diseases might raise or decrease serum ferritin levels up to more than 1500 µg/L.3 As there are no universally accepted criteria for ID, bone marrow biopsy remains the gold-standard investigation. However, bone marrow biopsy is generally avoided because it is invasive. So, other alternative markers are often used for ID diagnosis. Although serum ferritin show an acceptable specificity for ID anaemia diagnosis (72% to 88% in previous reports), some studies showed other markers, such as soluble transferrin receptor and reticulocyte haemoglobin content, with a higher specificity (92.9–100%).4, 5 These markers increase in tissue ID and are not sensitive to inflammation. Secondly, about 21% to 64% patients received anticoagulant or antiplatelet therapy as baseline. Long-term usage of these drugs might affect the function of the gastrointestinal system and/or favour blood loss with an effect on serum ferritin levels.2 Additionally, patients receiving oral iron treatment (2–11% in different groups) were not excluded. These therapy measurements might affect the results. Furthermore, there were significant differences in body mass index and diabetes across groups at baseline. Serum transferrin concentrations could be affected by the metabolic situations and nutrition.2, 6 All these confounding situations should be considered before the conclusion. Generally, we argue that additional data might further confirm the prognostic value of ID and anaemia in ambulatory patients with chronic heart failure.