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Accelerated atherosclerosis in patients with Wegener’s granulomatosis

K de Leeuw¹, J-S Sanders¹, C Stegeman², A Smit³, C G Kallenberg¹ and M Bijl¹

¹ Department of Clinical Immunology, University Hospital, Groningen, Netherlands
² Department of Nephrology, University Hospital, Groningen
³ Department of Vascular diseases, University Hospital, Groningen

Correspondence to:
Correspondence to:
MsKarina de Leeuw
Department of Internal Medicine, Division of Clinical Immunology, University Hospital, PO Box 30.001, 9700 RB Groningen, Netherlands; k.de.leeuw{at}int.azg.nl

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

Objective: To evaluate whether patients with Wegener’s granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors.

Methods: 29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima–media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease 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) and TIMP-1 were measured.

Results: IMT was increased in WG patients compared with 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).

Conclusions: Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised 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.

Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; BVAS, Birmingham vasculitis activity score; hsCRP, high sensitivity C reactive protein; IMT, intima–media thickness; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; VCAM-1, vascular cell adhesion molecule-1; vWF, von Willebrand factor; WG, Wegener’s granulomatosis; WTS, wall track system

Keywords: Wegener’s granulomatosis; atherosclerosis; endothelial activation; matrix metalloproteinases

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