Metabolic disorders induced by highly active antiretroviral therapy and their relationship with vascular remodeling of the brachial artery in a population of HIV-infected patients Rosario Rossi a, ⁎ , Annachiara Nuzzo a , Giovanni Guaraldi b , Nicola Squillace b , Gabriella Orlando b , Roberto Esposito b , Antonella Lattanzi a , Maria G. Modena a a Institute of Cardiology, University of Modena and Reggio Emilia. Policlinico Hospital, 41100 Modena, Italy b Infectious Diseases Clinic, University of Modena and Reggio Emilia. Policlinico Hospital, 41100 Modena, Italy Received 25 August 2008; accepted 17 February 2009 Abstract Antiretroviral therapy has positively modified the natural history of HIV infection; but this treatment can induce metabolic abnormalities, including dyslipidemia, fat redistribution, high blood pressure, and insulin resistance. The metabolic syndrome, a clustering of the metabolic disorders, is frequently detected among HIV patients, especially those on antiretroviral treatment. All the arteries can modify their diameter in response to a chronic injury. This process, defined vascular remodeling, was demonstrated for the brachial artery. It is well known that the diameter of the brachial artery was correlated with the number of the elements of the metabolic syndrome and was associated with the severity of coronary artery disease. On this basis, we postulate that brachial arterial enlargement may be a process potentially correlated with the metabolic disorders induced by antiretroviral therapy. We tested this hypothesis in a large population of HIV-infected patients in which we measured brachial artery diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic technique. Our population consisted of 570 patients, with a mean age of 46.3 ± 7.1 years. All the patients were chronically treated with highly active antiretroviral therapy. Brachial artery diameter was correlated with insulin resistance, evaluated by the homeostasis model assessment of insulin resistance index (r = 0.18, P b .0001). There was a significant linear increase in brachial artery diameter as the number of components of the metabolic syndrome increased: brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3 ± 7.2, 41.0 ± 6.8, 42.0 ± 7.3, and 43.8 ± 7.9 mm, respectively (P b .001 for trend). In multivariable logistic regression analysis, brachial artery diameter was independently correlated with the presence of metabolic syndrome. Our results are in line with the hypothesis that, among HIV-infected patients chronically treated with antiretroviral therapy, those with a larger brachial artery diameter are at high risk for metabolic disorders, including a more severe insulin resistance and the presence of metabolic syndrome. © 2009 Elsevier Inc. All rights reserved. 1. Introduction Combination highly active antiretroviral therapy (HAART) has positively modified the natural history of HIV infection, leading to a significant reduction in morbidity and mortality. However, long-term toxicity is recognized; and a variety of metabolic abnormalities, including dyslipidemia, fat redis- tribution, high blood pressure, and insulin resistance, has frequently been associated with this treatment [1-8]. The metabolic syndrome (MS), a clustering of the above-cited metabolic disorders, is frequently detected among HIV patients, especially those on HAART [9-11]. All the arteries can modify their diameter in response to a variety of stimuli, including hemodynamic changes or chronic injury. This process, defined vascular remodeling, was clearly demonstrated in patients with atherosclerosis [12-15]. The brachial artery, probably due to its favorable position, is one of the most studied artery in the body. It is well known that the diameter of the brachial artery was proportionally related with the number of the elements of the MS [16] and was associated with the severity of coronary artery disease [17]. On this basis, we postulate that brachial arterial Available online at www.sciencedirect.com Metabolism Clinical and Experimental 58 (2009) 927 – 933 www.metabolismjournal.com ⁎ Corresponding author. Tel.: +39 059 4224241; fax: +39 059 4224323. E-mail address: rossi.rosario@unimore.it (R. Rossi). 0026-0495/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2009.02.026