Fetuin-A serum levels in patients with aortic aneurysms of Marfan syndrome and atherosclerosis Zolta ´ n Szeberin * , Ma ´ tya ´ s Fehe ´ rva ´ ri * , Miklo ´ s Krepuska * , Astrid Apor † , Endre Rimely † , Hunor Sarkadi † , Ga ´bor Bı´ro ´ * , Pe ´ ter So ´ tonyi * , Ga ´ bor Sze ´ plaki † , Zolta ´ n Szabolcs ‡ , Zolta ´ n Proha ´ szka § , La ´ szlo ´ Kalabay ¶ and Gyo ¨ rgy Acsa ´ dy * * Department of Vascular Surgery, † Heart Center, ‡ Department of Cardiac Surgery, § Third Department of Internal Medicine, ¶ Department of Family Medicine, Semmelweis University, Budapest, Hungary ABSTRACT Background Fetuin-A is a glycoprotein that inhibits extraosseous and vascular calcification. Its serum level is lower in patients with atherosclerosis compared with healthy controls, but its role is unknown in aneurysmal diseases. The aim of our study was to investigate the association of serum fetuin-A levels with aortic aneurysms of different aetiology: Marfan syndrome and atherosclerosis. Material and methods In a single centre cross-sectional observational study, 105 patients (30 with atheroscle- rotic aortic aneurysm, 15 with Marfan syndrome, 30 with peripheral arterial disease and 30 healthy controls) were examined; sera were analysed for fetuin-A, standard markers of possible inflammation, lipid profile, kidney and hepatic disease and diabetes. Systemic atherosclerosis was assessed by carotid intima-media thickness (IMT) measurement and arterial calcification score of cardiac valves, carotids, aorta and femoral arteries determined by ultrasound. Results Serum fetuin-A levels (median and IQR) were significantly lower in the atherosclerotic aneurysm cohort than in patients with Marfan syndrome: 708 lg mL )1 (612–780) and 756 lg mL )1 (708–816), respectively, (P =0Æ0428). Fetuin-A levels were 754 lg mL )1 (713–777) in the control group and 654 lg mL )1 (600–756) in patients with peripheral arterial disease. Mean and maximum IMT, ACS values and homocysteine levels were significantly higher in patients with atherosclerosis: P <0Æ0001, P <0Æ0001, P <0Æ0001 and P =0Æ0034, respectively. There was no significant difference between aneurysm groups analysing the results of lipid profile and acute-phase markers. Conclusions The significantly lower serum level of fetuin-A in the atherosclerotic aneurysm group supports the protective role of fetuin-A in the evolution of arterial calcification. Keywords Aortic aneurysm, atherosclerosis, calcification, fetuin-A, Marfan syndrome. Eur J Clin Invest 2011; 41 (2): 176–182 Introduction Atherosclerotic patients with calcified arterial walls have a tendency to develop earlier and more severe progression of their disease. This leads to higher cardiovascular morbidity and mortality [1]. There is gathering evidence that fetuin-A (also known as alpha2-Heremans-Schmid glycoprotein, AHSG) plays an important role in the regulation of ectopic calcification [2,3]. Fetuin-A is reported as a systematically acting inhibitor of extraosseous calcification in AHSG knock- out mice [4,5]. Several studies report that lower fetuin-A serum levels associate with more severe atherosclerosis. Most of these data were collected from studies on patients with end-stage kidney disease requiring dialysis [6,7]. Only limited data are available in patients with normal kidney functions or moderate renal impairment and advanced atherosclerosis. There are a few studies about patients with coronary artery [8,9] and cardiac valve calcification [10] and patients with peripheral artery disease (PAD) [11], and information is especially scarce about the connection of fetuin-A and aortic atherosclerosis [12]. We found no report on examination of fetuin-A in patients with aneurysmal disease. 176 European Journal of Clinical Investigation Vol 41 DOI: 10.1111/j.1365-2362.2010.02393.x ORIGINAL ARTICLE