Anaemia in patients with heart failure
Anaemia is common in patients with heart failure. It is most often seen in women, the elderly and patients with renal dysfunction.57 It is associated with more severe symptoms, worse functional status and higher risk of morbidity and mortality.58,59
The prevalence of anaemia varies between 7–50% in study populations and heart failure registries due to varying definitions and patient selection for studies. In a systematic review of 34 studies, most of which used the World Health Organisation definition of anaemia (haemoglobin <13 g/dL for men; <12 g/dL for women), the prevalence of anaemia was 37% amongst 153,000 patients with heart failure.
When a patient with heart failure is identified as having anaemia, tests should be carried out to identify an underlying cause (occult blood loss, iron/vitamin B12/folate deficiency).21 However, often a specific cause cannot be found and the anaemia may be a consequence of multiple factors relating to the disease and co-morbidities (figure 6).

Chronic kidney disease
CKD is common among patients with chronic heart failure (18%).40 The primary cause of anaemia in patients with CKD is reduced erythropoietin (EPO) production but other factors, such as nutrient deficiency associated with renal dysfunction also play a role.
The prevalence of anaemia among patients with CKD is inversely proportional to estimated glomerular filtration rate (eGFR) (table 3).60

Supression of angiotensin II activity
ACE inhibitors may also contribute to anaemia in patients with heart failure.61
- Reduced angiotensin II activity causes dilation of the afferent arteriole of the glomerulus and increased renal blood flow which, in turn, reduces EPO secretion.
- Angiotensin II stimulates production of red blood cell precursor cells via activation of angiotensin II receptor type 1 on blast cells.62
- ACE inhibitors inhibit the breakdown of N-acetyl-seryl-aspartyl-lysyl-proline which suppresses haematopoetic stem cell proliferation.63
Haemodilution
Haemodilution occurs as a consequence of fluid retention in patients with heart failure,64 and is associated with anaemia in patients with heart failure independent of eGFR and EPO levels.65 It may account for as many as half the cases of anaemia in chronic heart failure.61
Effect of pro-inflammatory cytokines
Heart failure is a pro-inflammatory state associated with raised levels of tumour necrosis factor and interleukin-6 among other cytokines.66 Levels of these cytokines are inversely proportional to haemoglobin.67 Pro-inflammatory states reduce EPO secretion,68 and reduce GI absorption and the bioavailability of iron for haem production.69
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