Iron status in patients with chronic heart failure

Ewa Jankowska

Jolanta Malyszko

Hossein Ardehali

Ewa Koc-Zorawska

John McMurray+3 authors

Aims

The changes in iron status occurring during the course of heart failure (HF) and the underlying pathomechanisms are largely unknown. Hepcidin, the major regulatory protein for iron metabolism, may play a causative role. We investigated iron status in a broad spectrum of patients with systolic HF in order to determine the changes in iron status in parallel with disease progression, and to associate iron status with long-term prognosis.

Methods and results

Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 321 patients with chronic systolic HF [age: 61 ± 11 years, men: 84%, left ventricular ejection fraction: 31 ± 9%, New York Heart Association (NYHA) class: 72/144/87/18] at a tertiary cardiology centre and 66 age- and gender-matched healthy subjects. Compared with healthy subjects, asymptomatic HF patients had similar haematological status, but increased iron stores (evidenced by higher serum ferritin without distinct inflammation, P < 0.01) with markedly elevated serum hepcidin (P < 0.001). With increasing HF severity, patients in advanced NYHA classes had iron deficiency (ID) (reduced serum ferritin, low Tsat, high sTfR), iron-restricted erythropoiesis (reduced haemoglobin, high red cell distribution width), and inflammation (high serum high-sensitivity-C-reactive protein and interleukin 6), which was accompanied by decreased circulating hepcidin (all P < 0.001). In multivariable Cox models, low hepcidin was independently associated with increased 3-year mortality among HF patients (P < 0.001).

Conclusions

Increased level of circulating hepcidin characterizes an early stage of HF, and is not accompanied by either anaemia or inflammation. The progression of HF is associated with the decline in circulating hepcidin and the development of ID. Low hepcidin independently relates to unfavourable outcome.

^{Laboratory for Applied Research of Cardiovascular System, Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, ul. Weigla 5, 50-981, Wroclaw, Poland}

^{Centre for Heart Diseases, Military Hospital, Wroclaw, Poland}

^{Department of Nephrology and Transplantology, Bialystok Medical University, Bialystok, Poland}

^{Division of Cardiology, Department of Medicine, Northwestern University School of Medicine, Chicago, IL, USA}

^{Department of Renal Medicine, King's College Hospital, London, UK}

^{Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Medical University of Innsbruck, Innsbruck, Austria}

^{British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK}

^{Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany}

^{Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy}

^{Corresponding author. Tel/Fax: +48 71 7660 250, Email:}lp.corw.ma@akswoknaj.awe

Received 2012 Jul 18; Revised 2012 Sep 3; Accepted 2012 Oct 15.

Abstract

Aims

Methods and results

Conclusions

Keywords: Heart failure, Iron deficiency, Ferritin, Hepcidin, Prognosis

Abstract

Data are presented as means ± standard deviations, medians (with lower and upper quartiles), or numbers with percentages, where appropriate.

HF, heart failure; BMI, body mass index; CAD, coronary artery disease; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B type natriuretic peptide; GFR, glomerular filtration rate; hs-C-reactive protein, high-sensitivity C-reactive protein; IL-6, interleukin 6; ACE-I, angiotensin-converting enzyme-inhibitor; ARB, angiotensin receptor blocker; ICD, implanted cardioverter defibrillator; CRT, cardiac resynchronization therapy.

**P < 0.01, ***P < 0.001—patients with systolic HF compared with healthy subjects.

Data are presented as means ± standard deviations, medians (with lower and upper quartiles), where appropriate.

MCV, mean corpuscular volume; RDW, red cell distribution width; TIBC, total iron binding capacity; Tsat, transferrin saturation; sTfR, soluble transferrin receptor; hs-C-reactive protein, high-sensitivity C-reactive protein; IL-6, interleukin 6.

*P < 0.05, **P < 0.01, ***P < 0.001—healthy subjects compared with asymptomatic patients with systolic HF (NYHA class I).

HR, hazard ratio; CI, confidence interval; BMI, body mass index; HF, heart failure; CAD, coronary artery disease; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B type natriuretic peptide; hs-C-reactive protein, high-sensitivity C-reactive protein; GFR, glomerular filtration rate.

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