This Article Full Text Full Text (PDF) All Versions of this Article: 34/3/610    most recent 01.STR.0000058481.82639.EFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mayr, M. Articles by Xu, Q. Search for Related Content PubMed PubMed Citation Articles by Mayr, M. Articles by Xu, Q. Related Collections Pathophysiology Risk Factors

(Stroke. 2003;34:610.)
© 2003 American Heart Association, Inc.

Original Contributions

Increased Risk of Atherosclerosis Is Confined to CagA-Positive Helicobacter pylori Strains

Prospective Results From the Bruneck Study

Manuel Mayr, MD; Stefan Kiechl, MD; Michael A. Mendall, MD; Johann Willeit, MD; Georg Wick, MD Qingbo Xu, MD, PhD

From the Institute for Biomedical Aging Research, Austrian Academy of Sciences (M.M., G. W., Q. X.), and Department of Neurology, University Clinic (S.K., J.W.), Innsbruck, Austria, and Mayday University Hospital, London, UK (M.A.M.).

Correspondence to Professor Qingbo Xu, Department of Cardiological Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail q.xu{at}sghms.ac.uk

Background and Purpose— Accumulating evidence indicates that a variety of infections contribute to the pathogenesis of atherosclerosis, but there is controversy concerning the impact of Helicobacter pylori infections in atherosclerosis.

Methods— We evaluated seropositivity to H pylori and to its cytotoxin-associated gene A (CagA) product in a large, prospective, population-based study (n=684). Intima-media thickness and atherosclerosis of carotid arteries were thoroughly assessed by high-resolution duplex scanning.

Results— In our study population, H pylori infections defined by seropositivity have no relationship with levels of classic cardiovascular risk factors or markers of systemic inflammation, except for elevated levels of immune reactions to mycobacterial heat shock protein 65. The latter showed a trend toward highest levels in those harboring virulent H pylori strains (P=0.08). Common carotid artery intima-media thickness—both absolute values and changes between 1995 and 2000—were significantly enhanced in subjects seropositive to CagA but not in those infected with CagA-negative H pylori strains. There was a clear dose-response relation between anti-CagA antibodies and both intima-media thickness and atherosclerosis risk. Notably, the risk of atherosclerosis associated with CagA seropositivity was amplified by elevated C-reactive protein levels.

Conclusions— Infections with virulent CagA-bearing H pylori strains may contribute to the pathogenesis of early atherosclerosis by aggravating immune-inflammatory reactions.

Key Words: carotid arteries • Helicobacter pylori • infection • risk factors • seroepidemiologic studies

This article has been cited by other articles:

				M. Mayr, S. Kiechl, S. Tsimikas, E. Miller, J. Sheldon, J. Willeit, J. L. Witztum, and Q. Xu Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2436 - 2443. [Abstract] [Full Text] [PDF]

				A. Pietroiusti, M. Giuliano, A. Magrini, A. Bergamaschi, and A. Galante Cytotoxin-Associated Gene A Strains of Helicobacter Pylori Represent a Risk Factor for the Development of Microalbuminuria in Type 2 Diabetes. Diabetes Care, June 1, 2006; 29(6): 1399 - 1401. [Full Text] [PDF]

				M. Diomedi, A. Pietroiusti, M. Silvestrini, B. Rizzato, L. M. Cupini, F. Ferrante, A. Magrini, A. Bergamaschi, A. Galante, and G. Bernardi CagA-positive Helicobacter pylori strains may influence the natural history of atherosclerotic stroke Neurology, September 14, 2004; 63(5): 800 - 804. [Abstract] [Full Text] [PDF]

				B. Ludewig, P. Krebs, and E. Scandella Immunopathogenesis of atherosclerosis J. Leukoc. Biol., August 1, 2004; 76(2): 300 - 306. [Abstract] [Full Text] [PDF]

				M. R. Preusch, A. J. Grau, F. Buggle, C. Lichy, J. Bartel, C. Black, and J. Rudi Association Between Cerebral Ischemia and Cytotoxin-Associated Gene-A-Bearing Strains of Helicobacter pylori Stroke, August 1, 2004; 35(8): 1800 - 1804. [Abstract] [Full Text] [PDF]

				J. Zhu, R. J. Katz, A. A. Quyyumi, D. A. Canos, D. Rott, G. Csako, A. Zalles-Ganley, J. Ogunmakinwa, A. G. Wasserman, and S. E. Epstein Association of Serum Antibodies to Heat-Shock Protein 65 With Coronary Calcification Levels: Suggestion of Pathogen-Triggered Autoimmunity in Early Atherosclerosis Circulation, January 6, 2004; 109(1): 36 - 41. [Abstract] [Full Text] [PDF]

				M. Gabrielli, A. Santoliquido, F. Cremonini, V. Cicconi, M. Candelli, M. Serricchio, P. Tondi, R. Pola, G. Gasbarrini, P. Pola, et al. CagA-positive cytotoxic H. pylori strains as a link between plaque instability and atherosclerotic stroke Eur. Heart J., January 1, 2004; 25(1): 64 - 68. [Abstract] [Full Text] [PDF]