1 Department of Clinical Medicine - Department of Thoracic and Cardiovascular Surgery T, Department of Clinical Medicine, Health, Aarhus University2 Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid3 Hjerte-, Lunge- og Karkirurgi4 Hospital de Cruces, Bilbao5 INSERM U773, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Louis Mourier, Colombes6 U698 and UMR 1148, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris7 Inserm, U773, Univ Paris Diderot, Sorbonne Paris Cité, AP-HP, Biochemistry Department, Hôpital Bichat, Paris8 Vascular Surgery, Hospital Galdakao, Bilbao9 INSERM U773, Univ Versailles Saint Quentin-en-Yvelines, AP-HP, Hôpital Ambroise Paré10 Department of Internal Medicine VI, Medical University of Innsbruck11 Vascular Research Lab and Vascular Surgery, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)12 Department of Clinical Medicine - Department of Thoracic and Cardiovascular Surgery T, Department of Clinical Medicine, Health, Aarhus University
Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.
Thrombosis and Haemostasis, 2014, Vol 112, Issue 1, p. 87-95