Skip to main content
Top
Published in: Clinical Research in Cardiology 6/2017

Open Access 01-06-2017 | Original Paper

Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry

Authors: Stephan von Haehling, Uwe Gremmler, Michael Krumm, Frank Mibach, Norbert Schön, Jens Taggeselle, Johannes B. Dahm, Christiane E. Angermann

Published in: Clinical Research in Cardiology | Issue 6/2017

Login to get access

Abstract

Background

Iron deficiency (ID) and anaemia are common in heart failure (HF). The prospective, observational PReP registry (Prävalenz des Eisenmangels bei Patienten mit Herzinsuffizienz) studied prevalence and clinical impact of ID and anaemia in HF outpatients attending cardiology practices in Germany.

Methods and results

A total of 42 practices enrolled consecutive patients with chronic HF [left ventricular ejection fraction (LVEF) ≤45%]. ID was defined as serum ferritin <100 µg/l, or serum ferritin ≥100 µg/l/<300 µg/l plus transferrin saturation <20%, and anaemia as haemoglobin <13 g/dl (12 g/dl) in men (women). Exercise capacity was assessed using spiroergometry (69.4%) or 6-min walk test (30.4%). Amongst 1198 PReP-participants [69.0  ± 10.6 years, 25.3% female, New York Heart Association (NYHA) class 2.4  ± 0.5, LVEF 35.3 ± 7.2%], ID was found in 42.5% (previously unknown in all), and anaemia in 18.9% (previously known in 4.8%). ID was associated with female gender, lower body weight and haemoglobin, higher NYHA class and natriuretic peptide (NP) levels (all p < 0.05). ID was also more common in anaemic than non-anaemic patients (p < 0.0001), and 9.8% of PrEP-participants had both, ID and anaemia. On spiroergometry, ID independently predicted maximum exercise capacity even after multivariable adjustment, including anaemia (p = 0.0004). In all PrEP-participants, ID predicted reduced physical performance (adjusted for age, gender, anaemia, serum creatinine, C-reactive protein, LVEF, and NP level).

Conclusions

Despite high prevalence, ID was previously unknown in all PrEP-participants, and anaemia was often unappreciated. Given the clinical relevance, treatability, and independent association with reduced physical performance, ID should be considered more in real-world ambulatory healthcare settings and ID-screening be advocated to cardiologists in such populations.
Literature
1.
go back to reference von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD (2015) Iron deficiency and cardiovascular disease. Nat Rev Cardiol 12:659–669CrossRef von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD (2015) Iron deficiency and cardiovascular disease. Nat Rev Cardiol 12:659–669CrossRef
2.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P on behalt of the Authors/Task Force Members and Document Reviewers (2016) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC) developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 18:891–975CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P on behalt of the Authors/Task Force Members and Document Reviewers (2016) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC) developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 18:891–975CrossRefPubMed
4.
go back to reference Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 2001;131(Suppl 2):568S–579S Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 2001;131(Suppl 2):568S–579S
5.
go back to reference Turer AT, Malloy CR, Newgard CB, Podgoreanu MV (2010) Energetics and metabolism in the failing heart: important but poorly understood. Curr Opin Clin Nutr Metab Care 13:458–465CrossRefPubMedPubMedCentral Turer AT, Malloy CR, Newgard CB, Podgoreanu MV (2010) Energetics and metabolism in the failing heart: important but poorly understood. Curr Opin Clin Nutr Metab Care 13:458–465CrossRefPubMedPubMedCentral
6.
go back to reference Wish JB (2006) Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 1(Suppl 1):S4–S8CrossRefPubMed Wish JB (2006) Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 1(Suppl 1):S4–S8CrossRefPubMed
7.
go back to reference Pasricha SR, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK, Roger SD, Savoia HF, Tampi R, Thomson AR, Wood EM, Robinson KL (2010) Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 193:525–532PubMed Pasricha SR, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK, Roger SD, Savoia HF, Tampi R, Thomson AR, Wood EM, Robinson KL (2010) Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 193:525–532PubMed
8.
go back to reference Glaspy J, Cavill I (1999) Role of iron in optimizing responses of anemic cancer patients to erythropoietin. Int Soc Cell 13:461–473 Glaspy J, Cavill I (1999) Role of iron in optimizing responses of anemic cancer patients to erythropoietin. Int Soc Cell 13:461–473
10.
go back to reference Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P, for the FAIR-HF Trial Investigators (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefPubMed Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P, for the FAIR-HF Trial Investigators (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefPubMed
11.
go back to reference Ezekowitz JA, McAlister FA, Armstrong PW (2003) Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12,065 patients with new-onset heart failure. Circulation 107:223–225CrossRefPubMed Ezekowitz JA, McAlister FA, Armstrong PW (2003) Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12,065 patients with new-onset heart failure. Circulation 107:223–225CrossRefPubMed
12.
go back to reference Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, Tsagalou EP, Maroulidis GD, Alexopoulos GP, Kanakakis JE, Anastasiou-Nana MI (2006) Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 48:2485–2489CrossRefPubMed Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, Tsagalou EP, Maroulidis GD, Alexopoulos GP, Kanakakis JE, Anastasiou-Nana MI (2006) Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 48:2485–2489CrossRefPubMed
13.
go back to reference Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P (2010) Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 31:1872–1880CrossRefPubMed Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P (2010) Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 31:1872–1880CrossRefPubMed
14.
go back to reference Blanc B, Finch CA, Hallberg L, Nutritional anaemias (1968) Report of a WHO scientific group. WHO Tech Rep Ser 405:1–40 Blanc B, Finch CA, Hallberg L, Nutritional anaemias (1968) Report of a WHO scientific group. WHO Tech Rep Ser 405:1–40
15.
go back to reference Opasich C, Cazzola M, Scelsi L, DeFeo S, Bosimini E, Lagioia R, Febo O, Ferrari R, Fucilli A, Moratti R, Tramarin R, Tavazzi L (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26:2232–2237CrossRefPubMed Opasich C, Cazzola M, Scelsi L, DeFeo S, Bosimini E, Lagioia R, Febo O, Ferrari R, Fucilli A, Moratti R, Tramarin R, Tavazzi L (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26:2232–2237CrossRefPubMed
16.
go back to reference Adlbrecht C, Kommata S, Hu¨lsmann M, Szekeres T, Bieglmayer C, Strunk G, Karanikas G, Berger R, Mortl D, Kletter K, Maurer G, Lang IM, Pacher R (2008) Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body’s red cell volume. Eur Heart J 29:2343–2350CrossRefPubMed Adlbrecht C, Kommata S, Hu¨lsmann M, Szekeres T, Bieglmayer C, Strunk G, Karanikas G, Berger R, Mortl D, Kletter K, Maurer G, Lang IM, Pacher R (2008) Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body’s red cell volume. Eur Heart J 29:2343–2350CrossRefPubMed
17.
go back to reference Schou M, Bosselmann H, Gaborit F, Iversen K, Goetze JP, Soletomas G, Rasmussen J, Kistorp C, Kober L, Gustafsson F, Tonder N (2015) Iron deficiency: prevalence and relation to cardiovascular biomarkers in heart failure outpatients. Int J Cardiol 195:143–148CrossRefPubMed Schou M, Bosselmann H, Gaborit F, Iversen K, Goetze JP, Soletomas G, Rasmussen J, Kistorp C, Kober L, Gustafsson F, Tonder N (2015) Iron deficiency: prevalence and relation to cardiovascular biomarkers in heart failure outpatients. Int J Cardiol 195:143–148CrossRefPubMed
18.
go back to reference Ebner N, Jankowska EA, Ponikowski P, Lainscak M, Elsner S, Sliziuk V, Steinbeck L, Kube J, Bekfani T, Scherbakov N, Valentova M, Sandek A, Doehner W, Springer J, Anker SD, von Haehling S (2016) The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int J Cardiol 205:6–12CrossRefPubMed Ebner N, Jankowska EA, Ponikowski P, Lainscak M, Elsner S, Sliziuk V, Steinbeck L, Kube J, Bekfani T, Scherbakov N, Valentova M, Sandek A, Doehner W, Springer J, Anker SD, von Haehling S (2016) The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int J Cardiol 205:6–12CrossRefPubMed
19.
go back to reference Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ (2013) The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol 88:261–264CrossRefPubMed Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ (2013) The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol 88:261–264CrossRefPubMed
20.
go back to reference Pamuk GE, Top MŞ, Uyanık MŞ, Köker H, Akker M, Ak R, Yürekli ÖA, Çelik Y (2016) Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression? Wien Klin Wochenschr 128(Suppl 8):576–580CrossRefPubMed Pamuk GE, Top MŞ, Uyanık MŞ, Köker H, Akker M, Ak R, Yürekli ÖA, Çelik Y (2016) Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression? Wien Klin Wochenschr 128(Suppl 8):576–580CrossRefPubMed
21.
go back to reference Swedberg K, Young JB, Anand IS, Cehng S, Desai AS, Diaz R, Maggioni AP, MvMurray JJ, O’Connor,C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ, RED-HF Committees, RED- HF Investigators (2013) Treatment fo anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 368:1210–1219CrossRefPubMed Swedberg K, Young JB, Anand IS, Cehng S, Desai AS, Diaz R, Maggioni AP, MvMurray JJ, O’Connor,C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ, RED-HF Committees, RED- HF Investigators (2013) Treatment fo anemia with darbepoetin alfa in systolic heart failure. N Engl J Med 368:1210–1219CrossRefPubMed
22.
go back to reference Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Mori C, von Eisenhart Rothe B, Pocock S, Poole-Wilson PA, Ponikowski P; FAIR-HF committees and investigators (2009) Rationale and design of ferinject assessment in patients with iron deficiency and chronic heart failure (Fair-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail 11:1084–1091CrossRefPubMedPubMedCentral Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Mori C, von Eisenhart Rothe B, Pocock S, Poole-Wilson PA, Ponikowski P; FAIR-HF committees and investigators (2009) Rationale and design of ferinject assessment in patients with iron deficiency and chronic heart failure (Fair-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail 11:1084–1091CrossRefPubMedPubMedCentral
23.
go back to reference Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefPubMed Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefPubMed
24.
go back to reference Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh TA, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD (2014) Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency. ESC Heart Failure 1:52–58CrossRef Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh TA, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD (2014) Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency. ESC Heart Failure 1:52–58CrossRef
26.
go back to reference Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, Banasiak W, Filippatos G, Anker SD, Ponikowski P (2016) Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail 18:786–795CrossRefPubMed Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, Banasiak W, Filippatos G, Anker SD, Ponikowski P (2016) Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail 18:786–795CrossRefPubMed
27.
go back to reference Clevenger B, Gurusamy K, Klein AA, Murphy GJ, Anker SD, Richards T (2016) Systematic review and meta-analysis of iron therapy in anaemic adults without chronic kidney disease: updated and abridged Cochrane review. Eur J Heart Fail 18:774–785CrossRefPubMed Clevenger B, Gurusamy K, Klein AA, Murphy GJ, Anker SD, Richards T (2016) Systematic review and meta-analysis of iron therapy in anaemic adults without chronic kidney disease: updated and abridged Cochrane review. Eur J Heart Fail 18:774–785CrossRefPubMed
29.
go back to reference Cohen-Solal A, Leclercq C, Mebazaa A, De Groote P, Damy T, Isnard R, Galinier M (2014) Diagnosis and treatment of iron deficiency in patients with heart failure: expert position paper from French cardiologists. Arch Cardiovasc Dis 107:563–571CrossRefPubMed Cohen-Solal A, Leclercq C, Mebazaa A, De Groote P, Damy T, Isnard R, Galinier M (2014) Diagnosis and treatment of iron deficiency in patients with heart failure: expert position paper from French cardiologists. Arch Cardiovasc Dis 107:563–571CrossRefPubMed
Metadata
Title
Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry
Authors
Stephan von Haehling
Uwe Gremmler
Michael Krumm
Frank Mibach
Norbert Schön
Jens Taggeselle
Johannes B. Dahm
Christiane E. Angermann
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 6/2017
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-016-1073-y

Other articles of this Issue 6/2017

Clinical Research in Cardiology 6/2017 Go to the issue