Abstract
Background
The role of infection in the pathogenesis of atherosclerosis is still a matter of debate.
Aims
This study aimed to investigate the effect of CagA-positive Helicobacter pylori (H. pylori) strains infection on coronary atherosclerosis in patients with coronary heart disease and to elucidate how cytotoxin-associated gene A (CagA)-positive H. pylori strains infections were involved in coronary heart disease by examining the levels of serum lipid, high-sensitivity C-reactive protein (hsCRP) and oxidized low-density protein (oxLDL).
Methods
Recruited for this study were 159 patients with coronary heart disease. The severity of coronary heart disease was estimated by calculating the Gensini score. Serum oxLDL and hsCRP were examined in all subjects. Current H. pylori infection was determined in all participants by means of a modified (13C) urea breath test (>200 dpm classified as positive). IgG antibodies against CagA protein were analyzed by enzyme immunoassays. Antibody titers against CagA (≥8 U/ml) were classified as positive. All subjects were divided into three groups, including an uninfected group (n = 30), an H. pylori +CagA− group (n = 69), and an H. pylori +CagA+ group (n = 60).
Results
Significant differences were found among the three groups in levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum hsCRP, oxLDL, and severity of coronary atherosclerosis (p < 0.05). The levels of total cholesterol, LDL, apolipoprotein B, serum hsCRP, oxLDL were significantly elevated and the severity of coronary atherosclerosis was significantly increased in H. pylori +CagA+ group (p < 0.05).
Conclusions
More serious coronary atherosclerosis was observed in CHD patients with H. pylori +CagA+ infection. H. pylori +CagA+ infection might be involved in coronary atherosclerosis by modifying serum lipids, enhancing LDL oxidation, and activating the inflammatory responses.
Similar content being viewed by others
References
Sanders MK, Peura DA. Helicobacter pylori-associated diseases. Curr Gastroenterol Rep. 2002;4:448–454.
Gasbarrini A, Franceschi F, Cammarota G, Pola P, Gasbarrini G. Vascular and immunological disorders associated with Helicobacter pylori infection. Ital J Gastroenterol Hepatol. 1998;30:115–118.
Gasbarrini A, De Luca A, Fiore G, et al. Beneficial effects of Helicobacter pylori eradication on migraine. Hepatogastroenterology. 1998;45:765–770.
Gasbarrini A, Serricchio M, Tondi P, et al. Raynaud’s phenomenon and Helicobacter pylori infection. Int J Angiol. 1998;7:307–309.
Szklo M, Ding J, Tsai MY, et al. Individual pathogens, pathogen burden and markers of subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis. J Cardiovasc Med. 2009;10:747–751.
Kaklikkaya I, Kaklikkaya N, Buruk K, et al. Investigation of Chlamydia pneumoniae DNA, chlamydial lipopolisaccharide antigens, and Helicobacter pylori DNA in atherosclerotic plaques of patients with aortoiliac occlusive disease. Cardiovasc Pathol. 2006;15:105–109.
Ozdogru I, Kalay N, Dogan A, et al. The relationship between Helicobacter pylori IgG titre and coronary atherosclerosis. Acta Cardiol. 2007;62:501–505.
Chimienti G, Russo F, Lamanuzzi BL, et al. Helicobacter pylori is associated with modified lipid profile: impact on Lipoprotein(a). Clin Biochem. 2003;36:359–365.
Niemelä S, Karttunen T, Korhonen T, et al. Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations? Heart. 1996;75:573–575.
Hoffmeister A, Rothenbacher D, Bode G, et al. Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or Cytomegalovirus, is associated with an atherogenic, modified lipid profile. Arterioscler Thromb VascBiol. 2001;21:427–432.
Crabtree JE, Shallcross TM, Heatley RV. Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis. Gut. 1991;32(10):1473–1477.
Zito F, Di Castelnuovo A. Helicobacter pylori infection and the risk of myocardial infarction, role of fibrinogen and its genetic control. Thromb Haemost. 1999;82(1):14–18.
Kayo S, Ohsawa M, Ehara S, et al. Oxidized low-density lipoprotein levels circulating in plasma and deposited in the tissues: comparison between Helicobacter pylori-associated gastritis and acute myocardial infarction. Am Heart J. 2004;148:818–825.
Mayr M, Kiechl S, Tsimikas S, et al. Oxidized low-density lipoprotein autoantibodies, chronic infections, and carotid atherosclerosis in a population-based study. J Am Coll Cardiol. 2006;47:2436–2443.
Mayr M, Kiechl S, Willeit J, Wick G, Xu Q. Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and Cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation. 2000;102:833–839.
Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983;51:606.
Itabe H, Yamamoto H, Imanaka T, et al. Sensitive detection of oxidatively modified low-density lipoprotein using a monoclonal antibody. J Lipid Res. 1996;37:45–53.
Adiloglu AK, Ocal A, Can R, Duver H, Yavuz T, Aridogan BC. Detection of Helicobacter pylori and Chlamydia pneumoniae DNA in human coronary arteries and evaluation of the results with serologic evidence of inflammation. Saudi Med J. 2005;26:1068–1074.
Kowalski M, Pawlik M, Konturek JW, Konturek SJ. Helicobacter pylori infection in coronary artery disease. J Physiol Pharmol. 2006;57:101–111.
Niu YH, Xu CF, Shi JH, Ge JB. Relationship between infection burden and atherosclerosis and plaque feature. Zhonghua Xin Xue Guan Bing Za Zhi. 2005;33:303–306.
Michael R, Armin J, Buggle F, et al. Association between cerebral ischemia and cytotoxin-associated gene-a-bearing strains of Helicobacter pylori. Stroke. 2004;35:1800.
Zhang S, Guo Y, Ma Y, Teng Y. Cytotoxin-associated gene-A-seropositive virulent strains of Helicobacter pylori and atherosclerotic diseases: a systematic review. Chin Med J. 2008;121:946–951.
Mayr M, Kiechl S, Mendall MA, Willeit J, Wick G, Xu QB. Increased risk of atherosclerosis is confined to CagA-positive Helicobacter pylori strains prospective results from the Bruneck study. Stroke. 2003;34:610–615.
Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997;350:430–436.
Libby P, Egan D, Skarlatos S. Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation. 1997;96:4095–4103.
Mehta JL, Saldeen TGP, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol. 1998;31:1217–1225.
Covacci A, Censini S, Bugnoli M, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA. 1993;90:5791–5795.
Oshima T, Ozono R, Yano Y, et al. Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects. Am Coll Cardiol. 2005;45:1219–1222.
Saijo Y, Utsugi M, Yoshioka E, et al. Relationship of Helicobacter pylori infection to arterial stiffness in Japanese subjects. Hypertens Res. 2005;28:283–292.
Diomedi M, Pietroiusti A, Silvestrini M, et al. CagA positive Helicobacter pylori strains may influence the natural history of atherosclerotic stroke. Neurology. 2004;63:800–804.
Kiechl S, Egger G, Mayr M, et al. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation. 2001;103:1064–1070.
Zhu J, Quyyumi AA, Norman JE, Csako G, Epstein SE. Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels. J Am Coll Cardiol. 1999;34:1738–1743.
Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001;89:763–771.
Kiechl S, Lorenz E, Reindl M, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med. 2002;347:185–192.
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915–924.
Steinberg D, Witztum JL. Lipoproteins and atherogenesis: current concepts. JAMA. 1990;264:3047–3052.
Steinberg D. Low-density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272:20963–20966.
Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK. T lymphocytes from human atherosclerotic plaques recognize oxidized low-density lipoprotein. Proc Natl Acad Sci USA. 1995;92:3893–3897.
Smith C, Mitchinson MJ, Aruoma OI, Halliwell B. Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions. Biochem J. 1992;286:901–905.
Ehara S, Ueda M, Naruko T, et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with severity of acute coronary syndromes. Circulation. 2001;103:1955–1960.
Naruko T, Ueda M, Haze K, et al. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation. 2002;106:2894–2900.
Azumi H, Inoue N, Ohashi Y, et al. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol. 2002;22:1838–1844.
Huang B, Dong Y, Mai W, Li Y. Effect of Chlamydia pneumoniae infection and hyperlipidaemia on the expression of PPARgamma, P50 and c-Fos in aortic endothelial cells in C57bL/6 J mice. Acta Cardiol. 2005;60(1):43–49.
Acknowledgments
The authors are grateful to Mr. Wenbiao Zhu and Department of Medical Technology for their technical assistance. This study was supported by the Natural Scientific Research Fund of the Panyu District of Guangdong Province (No:2007-Z-79-1).
Conflicts of interest statement
We have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, B., Chen, Y., Xie, Q. et al. CagA-Positive Helicobacter pylori Strains Enhanced Coronary Atherosclerosis by Increasing Serum OxLDL and HsCRP in Patients with Coronary Heart Disease. Dig Dis Sci 56, 109–114 (2011). https://doi.org/10.1007/s10620-010-1274-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-010-1274-6