Background: Despite multiple factors correlating with the high prevalence of anaemia in heart failure, the prevailing mechanisms have yet to be established. The purpose of this study is to systematically review the literature and determine whether low circulating haemoglobin is primarily underlain by erythropoietin resistance or defective production in heart failure.
Design and methods: We conducted a systematic search of MEDLINE since its inception until May 2017 for articles reporting erythropoietin and haemoglobin concentrations in heart failure patients not treated with erythropoietin-stimulating agents. The primary outcome was the mean difference in observed/predicted (O/P) erythropoietin ratio between heart failure patients and normal reference values. Meta-regression analyses assessed the influence of potential moderating factors.
Results: Forty-one studies were included after systematic review, comprising a total of 3137 stable heart failure patients with mean age and left ventricular ejection fraction ranging from 52 years to 80 years and 21% to 59%. The O/P erythropoietin ratio was below reference values in 24 of 25 studies in anaemic heart failure patients ( n = 1094, range = 0.49-1.05), whereas only one out of 16 studies in non-anaemic heart failure patients presented a low O/P erythropoietin ratio ( n = 2043, range = 0.91-1.97). In studies comparing anaemic versus non-anaemic heart failure patients ( n = 1531), the mean O/P erythropoietin ratio was consistently reduced in anaemic heart failure patients (mean difference = -0.68, 95% confidence interval = -0.78, -0.57; p < 0.001). In meta-regression, the O/P erythropoietin ratio was negatively associated with age, female sex, left ventricular ejection fraction, inflammation and disease severity.
Conclusion: Anaemia in heart failure is overwhelmingly characterized by impaired erythropoietin production, which is exacerbated with age, female sex, left ventricular ejection fraction, inflammation and disease severity.
Keywords: Erythropoietin; anaemia; haemoglobin; heart failure; meta-analysis.