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Atherosclerosis 153 2000 231 – 239 High plasma levels of a- and b-carotene are associated with a lower risk of atherosclerosis Results from the Bruneck study Anna D’Odorico a , Diego Martines a , Stefan Kiechl b , Georg Egger b , Friedrich Oberhollenzer c , Piero Bonvicini d , Giacomo Carlo Sturniolo a , Remo Naccarato a , Johann Willeit b, a Department of Surgery and Gastroenterology, Uni6ersity of Padua, Padua, Italy b Department of Neurology, Uni6ersity of Innsbruck, Anichstr 35 , A- 6020 Innsbruck, Austria c Di6ision of Internal Medicine, Bruneck, Italy d Department of Clinical Biochemistry, Uni6ersity of Padua, Padua, Italy Received 13 July 1999; received in revised form 29 November 1999; accepted 7 January 2000 Abstract Background and purpose: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids a- and b- carotene, lutein, lycopene, zeaxanthin, b-cryptoxanthin, vitamins A and E, and atherosclerosis in the carotid and femoral arteries. Methods: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45 – 65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. Results: a- and b- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries P = 0.004 and with the 5-year incidence of atherosclerotic lesions in the carotid arteries P = 0.04. These findings were obtained after adjustment for other cardiovascular risk factors sex, age, LDL low density lipoproteins, ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein. Atherosclerosis risk gradually decreased with increasing plasma a- and b-carotene concentrations P = 0.004. No associations were found between vitamin A and E plasma levels and atherosclerosis. Conclusions: This study provides further epidemiological evidence of a protective role of high a- and b- carotene in early atherogenesis. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Antioxidants; a-Carotene; b-Carotene; Atherosclerosis; Carotid artery disease www.elsevier.comlocateatherosclerosis

1. Introduction

Cardiovascular disease is the leading cause of mor- bidity and mortality in industrialized countries and hyperlipidemia constitutes one of the main underlying risk conditions. A large number of epidemiological and experimental studies have contributed to the hypothesis that oxidative surface modifications of low-density lipo- protein LDL are crucial in the initiation of lipid-in- duced atherogenesis [1,2]. Modified LDL is more readily taken up by macrophages through the scavenger receptor, giving rise to the formation of foam cells and fatty streaks. Antioxidant substances disolved in LDL may be expected to counteract lipid peroxidation and decelerate atherosclerosis progression [3]. Strong sup- port for this concept derives from an animal model in which large amounts of dietary carotenoids protected against the development of atherosclerosis [4]. Furthermore, a variety of epidemiological studies [5 – 13] suggest inhibitory effects of high vitamin E and carotenoids on myocardial infarction, ischemic stroke and progression of coronary heart disease. These stud- ies focused on clinical complications of advanced atherosclerosis, and thus cannot furnish the proof of an Corresponding author. Tel.: + 43-512-5044279; fax: + 43-512- 5044260. E-mail address : johann.willeituibk.ac.at J. Willeit. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 0 0 0 0 4 0 3 - 2 antioxidant defense of carotenoids and vitamins [14]. Vitamin E, for example, could prevent progression of cardiovascular disease by potential blood clotting con- trol [15] and platelet adherence modulation properties [16,17]. Epidemiological surveys which directly address the effects of antioxidant levels on early atherosclerosis are needed to verify the key issue, but such evaluations are particularly scarce [18]. The current study was designed to investigate the association between carotenoids a- and b- carotene, lutein, lycopene, zeaxanthin, b-cryptoxanthin, vitamins A and E, and carotid and femoral artery atherosclerosis in a large random sample of men and women aged 45 – 65 years.

2. Methods

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