Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major Constadina Aggeli T , Charalambos Antoniades, Constadina Cosma, Christine Chrysohoou, Dimitris Tousoulis, Vasilios Ladis, Markisia Karageorga, Christos Pitsavos, Christodoulos Stefanadis Athens University Medical School, A’Cardiology Department, Hippokration Hospital, Greece Received 19 July 2004; received in revised form 8 November 2004; accepted 30 December 2004 Available online 5 March 2005 Abstract Background: Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. Methods: The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6F0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. Results: Patients had significantly lower levels of total cholesterol (125F4.5 vs. 207F7 mg/ml, pb0.01), ApoA1 (120F3 vs. 129F5 mg/ ml, pb0.05), ApoB (60.5F2 vs. 95F4 mg/ml, p b0.01), ApoE (3F2 vs. 4F0.2 mg/ml, p b0.01) and Lp(a) (7.9F1.3 vs. 14.5F3.2 mg/ml, p b0.01) than controls. IL-6 levels were significantly higher in patients (3.03F0.31 pg/ml) than controls (1.15F0.15 pg/ml, pb0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513F31 and 368F25.5 ng/ml, respectively) than controls (333F13.8 and 272F14.05 ng/ml, respectively, p b0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1F0.3 ml/100 ml tissue/min and 49F2.8%, respectively) than controls (8.26F0.32 ml/100 ml tissue/min and 86.3F5.57%, respectively, pb0.01 for both). Conclusions: Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Beta-thalassemia major; Endothelium; Cytokines; Adhesion molecules 1. Introduction Endothelium plays an important role in the modulation of vascular tone and structure while its dysfunction may be representative of vascular inflammation [1,2]. Endothelial dysfunction is the earliest measurable functional abnormal- ity of the vessel wall in atherogenetic process. Conse- quently, endothelial dysfunction appears to have detrimental functional consequences as well as adverse long term effects, including vascular remodelling [3]. It is widely known that in b-thalassemic patients the iron overload leads to toxicity in many organs including cardiovascular system [3–7]. Despite improved prognosis with iron chelation therapy, cardiac mortality and morbidity remain high in this particular population [6]. There is strong evidence of endothelial cell activation, and vascular complications in patients with beta-thalassemia are more frequent [4]. Activation of vascular endothelium is consid- ered an important facet of inflammation, vasculitis, and thrombosis [8]. 0167-5273/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2004.12.025 T Corresponding author. 47, Georgiou Papandreou, Athens, 15773 Greece E-mail address: caggeli@hol.gr (C. Aggeli). International Journal of Cardiology 105 (2005) 80 – 84 www.elsevier.com/locate/ijcard