Additional burden of iron deficiency in heart failure patients beyond the cardio‐renal anaemia syndrome: findings from the BIOSTAT‐CHF study

Abstract

Aims Whereas the combination of anaemia and chronic kidney disease (CKD) has been extensively studied in patients with heart failure (HF), the contribution of iron deficiency (ID) to this dysfunctional interplay is unknown. We aimed to assess clinical associates and pathophysiological pathways related to ID in this multimorbid syndrome. Methods and results We studied 2151 patients with HF from the BIOSTAT‐CHF cohort. Patients were stratified based on ID (transferrin saturation <20%), anaemia (World Health Organization definition) and/or CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). Patients were mainly men (73.3%), with a median age of 70.5 (interquartile range 61.4–78.1). ID was more prevalent than CKD and anaemia (63.3%, 47.2% and 35.6% respectively), with highest prevalence in those with concomitant CKD and anaemia (77.5% vs. 59.3%; p < 0.001). There was a considerable overlap in biomarkers and pathways between patients with isolated ID, anaemia or CKD, or in combination, with processes related to immunity, inflammation, cell survival and cancer amongst the common pathways. Key biomarkers shared between syndromes with ID included transferrin receptor, interleukin‐6, fibroblast growth factor‐23, and bone morphogenetic protein 6. Having ID, either alone or on top of anaemia and/or CKD, was associated with a lower overall summary Kansas City Cardiomyopathy Questionnaire score, an impaired 6‐min walk test and increased incidence of hospitalizations and/or mortality in multivariable analyses (all p < 0.05). Conclusion Iron deficiency, CKD and/or anaemia in patients with HF have great overlap in biomarker profiles, suggesting common pathways associated with these syndromes. ID either alone or on top of CKD and anaemia is associated with worse quality of life, exercise capacity and prognosis of patients with worsening HF.

Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

“…Another promising approach is the manipulation of the prolyl hydroxylase domain/hypoxia-inducible factor (PHD/HIF) pathway, which seems to be deranged in iron-deficient patients with HF [ 12 , 185 ]. Several HIFs stabilisers are being developed, some of which have entered/finished phase 3 of clinical trials, including Vadadustat, Daprodustat and Roxadustat [ 273 ].…”

“…Not only the presence of these comorbidities has been associated with worse prognosis, but also the severity, with advancing severity associated with higher mortality rates [ 10 ]. Although ID has traditionally been linked with anaemia, commonly referred to as iron deficiency anaemia (IDA), the two conditions do not necessarily coexist [ 12 ]. In fact, ID is poorly linked with red cell indices in HF, indicating that ID in these patients should be seen independently of erythropoietic status [ 13 ].…”

“…In acute HF, the prevalence of ID among non-anaemic patients is even higher at 57% in men and 79% in women [ 18 ]. Iron status, independently of haemoglobin (Hb) levels, is associated with reduced exercise capacity, impaired quality of life and increased risk of death and hospital (re-)admissions [ 12 , 14 , 16 , 19 , 20 , 21 ]. Intravenously correcting ID was shown to improve quality of life, exercise performance and symptoms regardless of Hb levels [ 22 , 23 , 24 , 25 ].…”

April 2023 at a glance: focus on diagnosis and comorbidities

“…Iron deficiency is common among patients with HF and intravenous (IV) iron improves quality of life and outcomes in them 22–26 . A meta‐analysis including 10 randomized controlled trials and 3373 patients evaluated the impact of IV iron administration on outcome.…”

Reply to ‘Exercise intolerance in heart failure: beyond mitochondrial dysfunction’. Letter regarding the article ‘Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?’

“…We acknowledge that iron deficiency may aggravate exercise intolerance in HF and that treatment of iron deficiency can improve exercise performance. 2,3 It should be borne in mind, however, that our review was directed at the potential therapeutic effect of physiological exercise in the context of HF, and we were therefore unable to take the confounding effects of the entire spectrum of possible comorbidities into account. Nevertheless, we agree with the authors that from a broader perspective, assessing iron levels and treating iron deficiency should be implemented alongside the advice to adhere to an exercise regimen.…”