Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. May 2005; 64(5): 753–759.
Published online Sep 16, 2004. doi:  10.1136/ard.2004.029033
PMCID: PMC1755479

Accelerated atherosclerosis in patients with Wegener's granulomatosis


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.

Full Text

The Full Text of this article is available as a PDF (114K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Libby Peter, Ridker Paul M, Maseri Attilio. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135–1143. [PubMed]
  • Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115–126. [PubMed]
  • Shimokawa H. Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol. 1999 Jan;31(1):23–37. [PubMed]
  • Szmitko Paul E, Wang Chao-Hung, Weisel Richard D, de Almeida John R, Anderson Todd J, Verma Subodh. New markers of inflammation and endothelial cell activation: Part I. Circulation. 2003 Oct 21;108(16):1917–1923. [PubMed]
  • Albert Michelle A, Glynn Robert J, Ridker Paul M. Plasma concentration of C-reactive protein and the calculated Framingham Coronary Heart Disease Risk Score. Circulation. 2003 Jul 15;108(2):161–165. [PubMed]
  • Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000 Mar 23;342(12):836–843. [PubMed]
  • Ridker Paul M, Rifai Nader, Rose Lynda, Buring Julie E, Cook Nancy R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557–1565. [PubMed]
  • Alkaabi JK, Ho M, Levison R, Pullar T, Belch JJF. Rheumatoid arthritis and macrovascular disease. Rheumatology (Oxford) 2003 Feb;42(2):292–297. [PubMed]
  • Del Rincón Inmaculada, Williams Ken, Stern Michael P, Freeman Gregory L, O'Leary Daniel H, Escalante Agustín. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum. 2003 Jul;48(7):1833–1840. [PubMed]
  • Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Côte R, Grover SA, Fortin PR, Clarke AE, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001 Oct;44(10):2331–2337. [PubMed]
  • Gonzalez-Juanatey Carlos, Llorca Javier, Testa Ana, Revuelta Javier, Garcia-Porrua Carlos, Gonzalez-Gay Miguel A. Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine (Baltimore) 2003 Nov;82(6):407–413. [PubMed]
  • Roman Mary J, Shanker Beth-Ann, Davis Adrienne, Lockshin Michael D, Sammaritano Lisa, Simantov Ronit, Crow Mary K, Schwartz Joseph E, Paget Stephen A, Devereux Richard B, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003 Dec 18;349(25):2399–2406. [PubMed]
  • Vlachoyiannopoulos PG, Kanellopoulos PG, Ioannidis JPA, Tektonidou MG, Mastorakou I, Moutsopoulos HM. Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology (Oxford) 2003 May;42(5):645–651. [PubMed]
  • Ara J, Mirapeix E, Arrizabalaga P, Rodriguez R, Ascaso C, Abellana R, Font J, Darnell A. Circulating soluble adhesion molecules in ANCA-associated vasculitis. Nephrol Dial Transplant. 2001 Feb;16(2):276–285. [PubMed]
  • Simantov R, Lo SK, Gharavi A, Sammaritano LR, Salmon JE, Silverstein RL. Antiphospholipid antibodies activate vascular endothelial cells. Lupus. 1996 Oct;5(5):440–441. [PubMed]
  • Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488–498. [PubMed]
  • Muller Kobold AC, van Wijk RT, Franssen CF, Molema G, Kallenberg CG, Tervaert JW. In vitro up-regulation of E-selectin and induction of interleukin-6 in endothelial cells by autoantibodies in Wegener's granulomatosis and microscopic polyangiitis. Clin Exp Rheumatol. 1999 Jul-Aug;17(4):433–440. [PubMed]
  • Stegeman CA, Tervaert JW, Huitema MG, de Jong PE, Kallenberg CG. Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin in patients with Wegener's granulomatosis. Relationship to disease activity and relevance during followup. Arthritis Rheum. 1994 Aug;37(8):1228–1235. [PubMed]
  • Booth AD, Jayne DRW, Kharbanda RK, McEniery CM, Mackenzie IS, Brown J, Wilkinson IB. Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation. 2004 Apr 13;109(14):1718–1723. [PubMed]
  • Filer AD, Gardner-Medwin JM, Thambyrajah J, Raza K, Carruthers DM, Stevens RJ, Liu L, Lowe SE, Townend JN, Bacon PA. Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa. Ann Rheum Dis. 2003 Feb;62(2):162–167. [PMC free article] [PubMed]
  • Booth AD, Wallace S, McEniery CM, Yasmin, Brown J, Jayne DRW, Wilkinson IB. Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum. 2004 Feb;50(2):581–588. [PubMed]
  • Faia Kerrie L, Davis Wendell P, Marone Adele J, Foxall Thomas L. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in hamster aortic atherosclerosis: correlation with in-situ zymography. Atherosclerosis. 2002 Feb;160(2):325–337. [PubMed]
  • Galis Zorina S, Khatri Jaikirshan J. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res. 2002 Feb 22;90(3):251–262. [PubMed]
  • Orbe J, Fernandez L, Rodríguez JA, Rábago G, Belzunce M, Monasterio A, Roncal C, Páramo José A. Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed. Atherosclerosis. 2003 Oct;170(2):269–276. [PubMed]
  • Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RW, Jr, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990 Aug;33(8):1101–1107. [PubMed]
  • Luqmani RA, Bacon PA, Moots RJ, Janssen BA, Pall A, Emery P, Savage C, Adu D. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994 Nov;87(11):671–678. [PubMed]
  • van Leeuwen MA, van Rijswijk MH, Westra J, de Jong HJ, Marrink J. C-reactieve proteïne; een dure bezinking? Ned Tijdschr Geneeskd. 1986 Aug 2;130(31):1391–1395. [PubMed]
  • de Groot E, Jukema JW, Montauban van Swijndregt AD, Zwinderman AH, Ackerstaff RG, van der Steen AF, Bom N, Lie KI, Bruschke AV. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS). J Am Coll Cardiol. 1998 Jun;31(7):1561–1567. [PubMed]
  • Howard G, Sharrett AR, Heiss G, Evans GW, Chambless LE, Riley WA, Burke GL. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. Stroke. 1993 Sep;24(9):1297–1304. [PubMed]
  • Montauban van Swijndregt AD, De Lange EE, De Groot E, Ackerstaff RG. An in vivo evaluation of the reproducibility of intima-media thickness measurements of the carotid artery segments using B-mode ultrasound. Ultrasound Med Biol. 1999 Mar;25(3):323–330. [PubMed]
  • Van Bortel LM, Vanmolkot FH, van der Heijden-Spek JJ, Bregu M, Staessen JA, Hoeks AP. Does B-mode common carotid artery intima-media thickness differ from M-model? Ultrasound Med Biol. 2001 Oct;27(10):1333–1336. [PubMed]
  • Khreiss Tarek, József Levente, Potempa Lawrence A, Filep János G. Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells. Circulation. 2004 Apr 27;109(16):2016–2022. [PubMed]
  • Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000 Oct 31;102(18):2165–2168. [PubMed]
  • Kai H, Ikeda H, Yasukawa H, Kai M, Seki Y, Kuwahara F, Ueno T, Sugi K, Imaizumi T. Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol. 1998 Aug;32(2):368–372. [PubMed]
  • Nomoto Kazumiki, Oguchi Sumito, Watanabe Ikuyoshi, Kushiro Toshio, Kanmatsuse Katsuo. Involvement of inflammation in acute coronary syndromes assessed by levels of high-sensitivity C-reactive protein, matrix metalloproteinase-9 and soluble vascular-cell adhesion molecule-1. J Cardiol. 2003 Nov;42(5):201–206. [PubMed]
  • Tziakas Dimitrios N, Chalikias Georgios K, Parissis John T, Hatzinikolaou Eleni I, Papadopoulos Elias D, Tripsiannis Grigorios A, Papadopoulou Evropi G, Tentes Ioannis K, Karas Spilios M, Chatseras Dimitrios I. Serum profiles of matrix metalloproteinases and their tissue inhibitor in patients with acute coronary syndromes. The effects of short-term atorvastatin administration. Int J Cardiol. 2004 Apr;94(2-3):269–277. [PubMed]
  • Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH. Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression. J Rheumatol. 2000 Dec;27(12):2761–2768. [PubMed]
  • Tchetverikov I, Lard LR, DeGroot J, Verzijl N, TeKoppele JM, Breedveld FC, Huizinga TWJ, Hanemaaijer R. Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis. Ann Rheum Dis. 2003 Nov;62(11):1094–1099. [PMC free article] [PubMed]
  • Matsuyama Akifumi, Sakai Naohiko, Ishigami Masato, Hiraoka Hisatoyo, Kashine Susumu, Hirata Ayumu, Nakamura Tadashi, Yamashita Shizuya, Matsuzawa Yuji. Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation. 2003 Sep 23;108(12):1469–1473. [PubMed]
  • Sorbi D, French DL, Nuovo GJ, Kew RR, Arbeit LA, Gruber BL. Elevated levels of 92-kd type IV collagenase (matrix metalloproteinase 9) in giant cell arteritis. Arthritis Rheum. 1996 Oct;39(10):1747–1753. [PubMed]

Figures and Tables

Figure 1
 Inflammation and endothelial activation markers. Empty circles represent controls, filled circles represent patients with Wegener's granulomatosis.
Figure 2
 Markers of vascular remodelling. Empty circles represent controls, filled circles represent patients with Wegener's granulomatosis.
Figure 3
 Correlation between intima–media thickness and age in controls and patients. Empty circles represent controls, filled circles represent patients with Wegener's granulomatosis.

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...