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      Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome

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          Abstract

          Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07–2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.

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          Assessing iron status: beyond serum ferritin and transferrin saturation.

          The increasing prevalence of multiple comorbidities among anemic patients with chronic kidney disease has made the use of serum ferritin and transferrin saturation more challenging in diagnosing iron deficiency. Because serum ferritin is an acute-phase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of patients with serum ferritin >800 ng/ml, suggesting iron overload, and transferrin saturation <20%, suggesting iron deficiency, has become more common. This article revisits the basis for the Kidney Disease Outcomes Quality Initiative recommendations regarding the use of serum ferritin and transferrin saturation in guiding iron therapy, then explores some of the newer alternative markers for iron status that may be useful when serum ferritin and transferrin saturation are insufficient. These newer tests include reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor, all of which have shown some promise in limited studies. Finally, the role of hepcidin, a hepatic polypeptide, in the pathophysiology of iron mobilization is reviewed briefly.
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            Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives

            Iron is a micronutrient essential for cellular energy and metabolism, necessary for maintaining body homoeostasis. Iron deficiency is an important co-morbidity in patients with heart failure (HF). A major factor in the pathogenesis of anaemia, it is also a separate condition with serious clinical consequences (e.g. impaired exercise capacity) and poor prognosis in HF patients. Experimental evidence suggests that iron therapy in iron-deficient animals may activate molecular pathways that can be cardio-protective. Clinical studies have demonstrated favourable effects of i.v. iron on the functional status, quality of life, and exercise capacity in HF patients. It is hypothesized that i.v. iron supplementation may become a novel therapy in HF patients with iron deficiency.
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              Detection, evaluation, and management of iron-restricted erythropoiesis.

              Progress in our understanding of iron-restricted erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted erythropoiesis.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                20 July 2018
                September 2018
                : 8
                : 3
                : 60
                Affiliations
                [1 ]Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany; t.zeller@ 123456uke.de (T.Z.); c.waldeyer@ 123456uke.de (C.W.); f.ojeda-echevarria@ 123456uke.de (F.O.); r.schnabel@ 123456uke.de (R.B.S.); sar.schaefer@ 123456uke.de (S.S.); alevaltay@ 123456web.de (A.A.); d.westermann@ 123456uke.de (D.W.); s.blankenberg@ 123456uke.de (S.B.)
                [2 ]German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, 20246 Hamburg, Germany; Karl.Lackner@ 123456unimedizin-mainz.de (K.J.L.); s.anker@ 123456cachexia.de (S.D.A.)
                [3 ]Department of Laboratory Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
                [4 ]Department of Cardiology (CVK) and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany
                Author notes
                [* ]Correspondence: m.karakas@ 123456uke.de ; Tel.: +49-40-7410-57975; Fax: +49-40-7410-55619
                [†]

                These authors contributed equally to this work.

                Article
                biomolecules-08-00060
                10.3390/biom8030060
                6163749
                30037035
                e5d4de9f-537d-4d83-85e7-755ae062d2bf
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 June 2018
                : 16 July 2018
                Categories
                Article

                iron deficiency,acute coronary syndrome,biomarker,prognosis

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