Letter to the Editor
Anemia and iron in heart failure – A brief comment
Anemia e ferro na insuficiência cardíaca – um breve comentário
José Pedro Lopes Nunes
Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Anemia and iron in heart failure – A brief comment" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "637" "paginaFinal" => "638" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José Pedro Lopes Nunes" "autores" => array:1 [ 0 => array:3 [ "nombre" => "José Pedro Lopes" "apellidos" => "Nunes" "email" => array:1 [ 0 => "jplnunes@med.up.pt" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Faculdade de Medicina da Universidade do Porto, Porto, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Anemia e ferro na insuficiência cardíaca – um breve comentário" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">I read with interest a letter mentioning our paper on “Anti-troponin I antibodies in renal transplant patients”, recently published.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Since the text is on a different topic, iron metabolism in heart failure, I will start by briefly commenting on this latter theme.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Medical textbooks have traditionally paid a considerable degree of attention to anemia and to iron deficiency. The underlying line of reasoning is that as iron is an essential element for the production of erythrocytes, insufficient body iron stores may lead to anemia, a situation that can be corrected by the administration of iron. Conventional medical wisdom has been that it is better to have a hemoglobin concentration in the normal range, rather than a lower one.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Data obtained in chronic renal failure patients with the use of erythropoiesis-stimulating agents (compared to placebo) caused a shift in medical thinking on the subject under consideration. Studies by Singh et al.,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> Drueke et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> and Pfeffer et al.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> have clearly shown that normal or near-normal values for hemoglobin lead to worse outcomes in patients with chronic renal failure, compared to lower values, leading to the current policy of avoiding hemoglobin values greater than 11.5 g/dl in these patients (therefore, normal is not always better).</p><p id="par0020" class="elsevierStylePara elsevierViewall">It was not until the turn of the millennium that an important regulator of iron metabolism<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a> was discovered – hepcidin.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6,7</span></a> As iron is important not only for human cells but also for invading microbial cells, the human body has a hepcidin-based mechanism to withdraw iron from the circulation in the presence of infection.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">5</span></a> Many inflammatory states would appear to be interpreted as stimuli for the action of hepcidin – giving rise to the so-called anemia of chronic disease. In a study carried out in preschool children in Africa (in a region with a high incidence of malaria), Sazawal et al. showed that routine prophylactic supplementation with iron and folic acid resulted in an increased risk of severe illness and death.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">With regard to heart failure, a condition frequently associated with anemia (and also with inflammation<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">9</span></a>), Swedberg et al. showed that darbepoetin alfa did not improve clinical outcomes in this setting.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> Adverse thromboembolic events were in fact increased in the intervention patient group.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> Anemia in heart failure may have different types of causes, one of which is the action of angiotensin-converting enzyme inhibitors.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Enalapril has been shown to increase the incidence of anemia in patients with heart failure.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Hepcidin was shown to be decreased in patients with heart failure and anemia,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> and has an uncertain role in this disease (unlike the case of hemodialysis patients, who have increased hepcidin levels<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">13</span></a>).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Anemia is associated with increased mortality in patients with heart failure, however it is unclear whether it is a marker or a mediator of increased mortality risk in this setting.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> Ferric carboxymaltose has been used in patients with heart failure and “iron deficiency”, with improvement in symptoms, functional capacity, and quality of life.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">15,16</span></a> However, data are available for only up to one year of therapy, and the longer-term effects of ferric carboxymaltose are unclear. Iron deficiency was diagnosed if ferritin <100 ng/ml or 100–299/300 ng/ml if transferrin saturation <20%, meaning that it is uncertain whether total body iron stores were decreased in all patients studied.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">15,16</span></a> “Iron deficiency”, under the same criteria, has been shown to act as a marker for an unfavorable prognosis in patients with heart failure.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">17,18</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Getting back to the comment on our text,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> we did not report that “the levels of antibodies were associated with reduced left ventricular ejection fraction”, neither did we state that “inflammatory mediators such as antibodies can be used as a marker of cardiac dysfunction”.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Moreover, I would certainly not agree with the concept that erythropoietin “seems to be an efficient therapy” for heart failure (as the data presented above<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">10</span></a> show).</p><p id="par0045" class="elsevierStylePara elsevierViewall">However, we did publish a case report,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> mentioned in our text, in which high titers of anti-troponin I antibodies were associated with the partial reversibility of a clinical picture of dilated cardiomyopathy, after immunosuppressive drugs were used. We presented the hypothesis that “the syndrome of reversible cardiomyopathy seen after renal transplantation is associated with immunosuppression therapy acting on immunological mechanisms previously at play”.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The speculation that anti-troponin I antibodies, acting as inflammatory mediators, could “lead to the inhibition of iron absorption at the duodenal level” – and this would seem to be the major point to be considered in the text – is worthy of consideration, in my view.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0100" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-troponin I antibodies in renal transplant patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.P.L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 5 | 10 |
| 2024 October | 34 | 24 | 58 |
| 2024 September | 44 | 26 | 70 |
| 2024 August | 34 | 24 | 58 |
| 2024 July | 45 | 26 | 71 |
| 2024 June | 32 | 18 | 50 |
| 2024 May | 30 | 26 | 56 |
| 2024 April | 21 | 22 | 43 |
| 2024 March | 63 | 20 | 83 |
| 2024 February | 40 | 30 | 70 |
| 2024 January | 18 | 30 | 48 |
| 2023 December | 15 | 23 | 38 |
| 2023 November | 23 | 15 | 38 |
| 2023 October | 25 | 24 | 49 |
| 2023 September | 21 | 16 | 37 |
| 2023 August | 16 | 15 | 31 |
| 2023 July | 17 | 12 | 29 |
| 2023 June | 17 | 14 | 31 |
| 2023 May | 31 | 17 | 48 |
| 2023 April | 13 | 9 | 22 |
| 2023 March | 15 | 23 | 38 |
| 2023 February | 18 | 21 | 39 |
| 2023 January | 17 | 12 | 29 |
| 2022 December | 14 | 24 | 38 |
| 2022 November | 18 | 15 | 33 |
| 2022 October | 20 | 12 | 32 |
| 2022 September | 15 | 29 | 44 |
| 2022 August | 24 | 25 | 49 |
| 2022 July | 24 | 26 | 50 |
| 2022 June | 15 | 18 | 33 |
| 2022 May | 15 | 29 | 44 |
| 2022 April | 22 | 21 | 43 |
| 2022 March | 21 | 23 | 44 |
| 2022 February | 16 | 18 | 34 |
| 2022 January | 15 | 22 | 37 |
| 2021 December | 11 | 22 | 33 |
| 2021 November | 22 | 30 | 52 |
| 2021 October | 38 | 36 | 74 |
| 2021 September | 18 | 23 | 41 |
| 2021 August | 24 | 26 | 50 |
| 2021 July | 14 | 25 | 39 |
| 2021 June | 15 | 18 | 33 |
| 2021 May | 32 | 38 | 70 |
| 2021 April | 23 | 21 | 44 |
| 2021 March | 59 | 16 | 75 |
| 2021 February | 41 | 12 | 53 |
| 2021 January | 21 | 11 | 32 |
| 2020 December | 25 | 5 | 30 |
| 2020 November | 23 | 10 | 33 |
| 2020 October | 11 | 8 | 19 |
| 2020 September | 26 | 13 | 39 |
| 2020 August | 12 | 7 | 19 |
| 2020 July | 33 | 8 | 41 |
| 2020 June | 14 | 12 | 26 |
| 2020 May | 44 | 2 | 46 |
| 2020 April | 18 | 5 | 23 |
| 2020 March | 33 | 13 | 46 |
| 2020 February | 30 | 13 | 43 |
| 2020 January | 23 | 4 | 27 |
| 2019 December | 21 | 6 | 27 |
| 2019 November | 33 | 6 | 39 |
| 2019 October | 29 | 6 | 35 |
| 2019 September | 11 | 6 | 17 |
| 2019 August | 27 | 7 | 34 |
| 2019 July | 24 | 12 | 36 |
| 2019 June | 16 | 11 | 27 |
| 2019 May | 32 | 6 | 38 |
| 2019 April | 14 | 13 | 27 |
| 2019 March | 19 | 14 | 33 |
| 2019 February | 30 | 11 | 41 |
| 2019 January | 30 | 8 | 38 |
| 2018 December | 32 | 8 | 40 |
| 2018 November | 76 | 13 | 89 |
| 2018 October | 157 | 7 | 164 |
| 2018 September | 31 | 19 | 50 |
| 2018 August | 25 | 9 | 34 |
| 2018 July | 22 | 5 | 27 |
| 2018 June | 17 | 3 | 20 |
| 2018 May | 56 | 9 | 65 |
| 2018 April | 35 | 1 | 36 |
| 2018 March | 52 | 9 | 61 |
| 2018 February | 35 | 1 | 36 |
| 2018 January | 46 | 6 | 52 |
| 2017 December | 100 | 7 | 107 |
| 2017 November | 13 | 11 | 24 |
| 2017 October | 22 | 14 | 36 |
| 2017 September | 19 | 8 | 27 |
| 2017 August | 27 | 12 | 39 |
| 2017 July | 16 | 8 | 24 |
| 2017 June | 19 | 24 | 43 |
| 2017 May | 21 | 6 | 27 |
| 2017 April | 31 | 1 | 32 |
| 2017 March | 36 | 28 | 64 |
| 2017 February | 24 | 9 | 33 |
| 2017 January | 20 | 4 | 24 |
| 2016 December | 29 | 9 | 38 |
| 2016 November | 27 | 4 | 31 |
| 2016 October | 16 | 6 | 22 |
| 2016 September | 14 | 11 | 25 |
| 2016 August | 13 | 2 | 15 |
| 2016 July | 10 | 6 | 16 |
| 2016 June | 12 | 6 | 18 |
| 2016 May | 16 | 5 | 21 |
| 2016 April | 9 | 5 | 14 |
| 2016 March | 9 | 15 | 24 |
| 2016 February | 20 | 13 | 33 |
| 2016 January | 27 | 15 | 42 |
| 2015 December | 17 | 11 | 28 |
| 2015 November | 27 | 15 | 42 |
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