Accelerated atherosclerosis in patients with Wegener's granulomatosis

Karina de Leeuw ^1*, Jan Stephan F. Sanders ¹, Coen A Stegeman ¹, Andries J Smit ¹, CGM Kallenberg ² and Marc Bijl ³

¹ Academic Hospital Groningen, The Netherlands
² University Hospital, The Netherlands
³ Dept of Clinical Immunology, The Netherlands

^* To whom correspondence should be addressed. E-mail: k.de.leeuw{at}int.azg.nl.

Accepted 10 September 2004

Abstract

Background: Several autoimmune diseases are complicated by excess cardiovascular disease (CVD). In addition to traditional risk factors, non-traditional risk factors, such as endothelial activation and excessive vascular remodelling, might be determinant factors in the progression of atherosclerosis in patients with an autoimmune disease.

Objectives: To evaluate whether patients with Wegener's Granulomatosis (WG) have increased prevalence of atherosclerosis and to determine predisposing factors. Methods: Twenty-nine WG patients (19 men, age 53 ± 14 years, mean ± standard deviation) with inactive disease and 26 controls (16 men, age 53 ± 15 years) were included. Common carotid intima media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for CVD were determined. High- sensitivity C-reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1 and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) as well as TIMP-1 were measured.

Results: IMT was increased in WG patients compared to controls (p<0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs and TIMP-1 were increased in WG patients (p<0.05).

Conclusion: Increased IMT found in WG patients can not be explained by increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the elevated levels of hsCRP, MMPs and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.

Keywords: intima media thickness, Wegener's granulomatosis, atherosclerosis, endothelial activation, matrix metalloproteinases

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