ABC | Volume 111, Nº2, August 2018

Original Article Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome Tatiana Duarte, Sara Gonçalves, Catarina Sá, Rita Rodrigues, Rita Marinheiro, Marta Fonseca, Filipe Seixo, Rui Caria Centro Hospitalar de Setúbal EPE, Setúbal - Portugal Mailing Address: Tatiana Duarte • Rua José Antonio Cabrita Batista,14 1DTO 2830-204 Barreiro, Setubal - Portugal E-mail: tatiana.isabel.duarte@gmail.com Manuscript received February 12, 2017, revised manuscript September 27, 2017, accepted May 01, 2018 DOI: 10.5935/abc.20180116 Abstract Background: Iron metabolism disorders have been associated with an increased risk of cardiovascular events. However, the prognostic impact on patients (pts) with acute coronary syndrome (ACS) has yet to be clarified. Objective: To determine the prognostic value of serum iron and ferritin levels in pts with ACS in the short and long-term. Methods: Consecutive pts admitted to a coronary care unit with a diagnosis of ACS, for a period of 2 years, were evaluated. The population was divided into tertiles of serum iron and ferritin distribution. The primary adverse events were the occurrence of in-hospital death or heart failure (HF) and death or HF at 1 year of follow-up. Results: We studied 280 pts (73% males; mean age 68 ± 13 years). The mean levels of serum iron and ferritin were 59 ± 34 mcg/dL and 205 ± 185 ng/mL, respectively. Patients included in the 1 st tertile of serum iron (≤ 40 mcg/dL) had a higher rate of adverse events, in-hospital and after 1 year. Lower and higher levels of ferritin (1 st and 3 rd tertiles, ≤ 110; >219 ng/ml, respectively) were associated with a higher incidence of HF during hospitalization and death at 1 year. A ferritin value >316 ng /mL was an independent risk factor for death at 1 year (adjusted OR: 14; 95%CI: 2.6 to 75.9). Conclusion: In this population, iron metabolism alterations were associated with a higher rate of adverse events and higher ferritin levels constituted an independent mortality predictor in the long-term. (Arq Bras Cardiol. 2018; 111(2):144-150) Keywords: Acute Coronary Syndrome; Iron Metabolism Disorders; Prognostic. Introduction Iron is an important micronutrient in cell metabolism, necessary for body homeostasis. 1 Iron deficiency affects more than one-third of the world’s population and is often a chronic disease complication (inflammatory bowel disease, chronic kidney disease, Parkinson's disease, rheumatoid arthritis) and plays a role in the sympathetic nervous system activation, as well as in ventricular hypertrophy and dilation. 1 According to the EMPIRE study, 1 in 3 Portuguese individuals have iron deficiency. 2 Iron deficiency is an important comorbidity factor inchronicheart failure (HF), aswell as inHFdecompensation periods, regardless of the presence of anemia. 1,3 The CONFIRM-HF study demonstrated a favorable effect on the functional capacity and quality of life of HF patients, as well as the reduction in the number of hospitalizations for decompensated HF in patients submitted to intravenous iron therapy. 1,3,4 Meanwhile, the debate between the role of ferritin and iron in the atherosclerosis metabolism persists, and the function of iron metabolism in coronary disease is unclear. Although small, there are studies that consider iron a proatherogenic agent for its role in free radical formation, with consequent oxidative stress at the vascular level. 5,6 Studies in animals have confirmed that chronic iron administration accelerates thrombus formation. 6 On the other hand, low iron levels may be associated with ischemia and major cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). 5 In a recent study, Steen et al. failed to establish any association between iron and the risk of myocardial infarction, as well as recurrent ischemic events. 7 Ferritin is considered by some studies as a cytoprotective agent, yet multivariate analyses have shown that low ferritin levels are predictors of 30-day MACE in patients with ACS. 5,8 Despite the several studies, the controversy over the role of iron in ACS persists, and the true correlation between iron and atherosclerotic disease is yet to be determined. In the present study, we aim to determine the short- and long-term prognostic value of serum iron and ferritin levels in patients admitted for ACS. 144