The physiological consequences of chronic heart failure are multi-faceted, with several tightly controlled and inter-related processes disturbed. Erythropoiesis and hepcidin-regulated iron transport are just two processes involved in iron homeostasis that are detrimentally altered in patients with chronic heart failure and ultimately contribute to the development of functional iron deficiency1. Other factors that may lead to iron deficiency in chronic heart failure, such as impaired intestinal absorption, are described in the 'Iron Essentials' section of this website.
Increased Pro-Inflammatory Cytokines
Healthy adults have a delicate balance of pro-inflammatory and anti-inflammatory factors, which ensures that a wide range of processes are properly regulated. This relationship is dynamic and changes to meet the body’s needs, for example following bacterial infection.
In chronic heart failure, there is an imbalance that favours the production of pro-inflammatory factors. These factors stimulate the secretion of proteins, such as hepcidin and erythropoeitin, which has a detrimental effect on iron homeostasis.
Erythropoiesis is the process by which red blood cells are formed. It therefore affects the amount of iron circulating in the blood as haemoglobin.
Erythropoiesis is impaired in patients with chronic heart failure, causing a reduction in haemoglobin and, consequently, the pool of circulating iron.
Disturbed Hepcidin Production
Hepcidin is a peptide hormone secreted by the liver. Hepcidin inhibits iron transport out of macrophages, restricting the mobilisation of iron stores when functional iron is plentiful.
Hepcidin production is increased in the early stages of heart failure, when patients are asymptomatic. This results in inadequate mobilisation of storage iron when levels of circulating iron are low.
Circulating hepcidin decreases with increasing disease severity. Low hepcidin levels have been independently associated with unfavourable outcome.
Functional Iron Deficiency
In chronic heart failure, both the circulating iron and functional iron (i.e. the iron bound to functional proteins) pools are reduced by 15-35%. By contrast, storage iron is increased by approximately 24%, indicating that iron is preferentially withdrawn from circulation and sequestered into storage. This results in a deficit of circulating – and subsequently functional – iron.