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. 2000 Sep;84(3):267–271. doi: 10.1136/heart.84.3.267

Significant association of cagA positive Helicobacter pylori strains with risk of premature myocardial infarction

M Gunn 1, J Stephens 1, J Thompson 1, B Rathbone 1, N Samani 1
PMCID: PMC1760960  PMID: 10956287

Abstract

OBJECTIVE—To investigate whether genetic diversity of Helicobacter pylori influences its association with coronary heart disease, and specifically whether the risk is confined to infection with the more virulent strains bearing the cytotoxin associated gene-A (cagA) antigen.
DESIGN AND SETTING—Case-control study in hospital admitting unselected patients with myocardial infarction.
METHODS AND SUBJECTS—Serological status for cagA and H pylori were determined in 342 cases of acute myocardial infarction and 214 population based control subjects free of clinical coronary heart disease.
RESULTS—38.0% of cases and 30.8% of controls were cagA seropositive (odds ratio 1.38, 95% confidence interval (CI) 0.94 to 2.01, p = 0.08). In subjects < 65 years old (153 cases, 153 controls), cagA seropositivity was associated with a 1.80-fold increase (95% CI 1.07 to 3.03, p = 0.02) in myocardial infarction risk, which increased further to 2.25-fold (95% CI 1.12 to 4.53, p = 0.01) in subjects < 55 years. There was no significant association of cagA status with classical coronary heart disease risk factors. H pylori seropositivity was present in 60.2% of cases and 53.7% of controls (odds ratio 1.12, 95% CI 0.83 to 1.51, p = 0.43). H pylori seropositivity was not increased in young cases and did not show any interaction with age.
CONCLUSIONS—The association of chronic H pylori infection with risk of myocardial infarction appears to be restricted to cagA bearing strains. The association is age dependent and stronger in younger subjects. Genetic heterogeneity of H pylori may explain some of the discordant findings with regard to the association of H pylori with coronary heart disease.


Keywords: coronary heart disease; risk factors; Helicobacter pylori

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Figure 1  .

Figure 1  

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Age dependency of the association of cagA positive strains of H pylori with risk of myocardial infarction. The odds ratio estimates for risk of myocardial infarction associated with cagA seropositivity for different age cut off values from the Mantel-Haenszel analysis adjusted for age and sex are shown in the line with the closed circles (with 95% confidence intervals in dotted lines). The corresponding estimates from the logistic regression are shown by the solid line.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blaser M. J., Chyou P. H., Nomura A. Age at establishment of Helicobacter pylori infection and gastric carcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res. 1995 Feb 1;55(3):562–565. [PubMed] [Google Scholar]
  2. Blaser M. J., Perez-Perez G. I., Kleanthous H., Cover T. L., Peek R. M., Chyou P. H., Stemmermann G. N., Nomura A. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995 May 15;55(10):2111–2115. [PubMed] [Google Scholar]
  3. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648–14653. doi: 10.1073/pnas.93.25.14648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ching C. K., Wong B. C., Kwok E., Ong L., Covacci A., Lam S. K. Prevalence of CagA-bearing Helicobacter pylori strains detected by the anti-CagA assay in patients with peptic ulcer disease and in controls. Am J Gastroenterol. 1996 May;91(5):949–953. [PubMed] [Google Scholar]
  5. Danesh J., Collins R., Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997 Aug 9;350(9075):430–436. doi: 10.1016/S0140-6736(97)03079-1. [DOI] [PubMed] [Google Scholar]
  6. Danesh J., Peto R. Risk factors for coronary heart disease and infection with Helicobacter pylori: meta-analysis of 18 studies. BMJ. 1998 Apr 11;316(7138):1130–1132. doi: 10.1136/bmj.316.7138.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Danesh J., Youngman L., Clark S., Parish S., Peto R., Collins R. Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. BMJ. 1999 Oct 30;319(7218):1157–1162. doi: 10.1136/bmj.319.7218.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Entman M. L., Ballantyne C. M. Inflammation in acute coronary syndromes. Circulation. 1993 Aug;88(2):800–803. doi: 10.1161/01.cir.88.2.800. [DOI] [PubMed] [Google Scholar]
  9. Fyfe A. I., Rothenberg L. S., DeBeer F. C., Cantor R. M., Rotter J. I., Lusis A. J. Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes. Circulation. 1997 Nov 4;96(9):2914–2919. doi: 10.1161/01.cir.96.9.2914. [DOI] [PubMed] [Google Scholar]
  10. Graham D. Y., Malaty H. M., Evans D. G., Evans D. J., Jr, Klein P. D., Adam E. Epidemiology of Helicobacter pylori in an asymptomatic population in the United States. Effect of age, race, and socioeconomic status. Gastroenterology. 1991 Jun;100(6):1495–1501. doi: 10.1016/0016-5085(91)90644-z. [DOI] [PubMed] [Google Scholar]
  11. Haverkate F., Thompson S. G., Pyke S. D., Gallimore J. R., Pepys M. B. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet. 1997 Feb 15;349(9050):462–466. doi: 10.1016/s0140-6736(96)07591-5. [DOI] [PubMed] [Google Scholar]
  12. Koenig W., Rothenbacher D., Hoffmeister A., Miller M., Bode G., Adler G., Hombach V., März W., Pepys M. B., Brenner H. Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response. Circulation. 1999 Dec 7;100(23):2326–2331. doi: 10.1161/01.cir.100.23.2326. [DOI] [PubMed] [Google Scholar]
  13. Kuller L. H., Tracy R. P., Shaten J., Meilahn E. N. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol. 1996 Sep 15;144(6):537–547. doi: 10.1093/oxfordjournals.aje.a008963. [DOI] [PubMed] [Google Scholar]
  14. Kurata J. H., Nogawa A. N. Meta-analysis of risk factors for peptic ulcer. Nonsteroidal antiinflammatory drugs, Helicobacter pylori, and smoking. J Clin Gastroenterol. 1997 Jan;24(1):2–17. doi: 10.1097/00004836-199701000-00002. [DOI] [PubMed] [Google Scholar]
  15. Liuzzo G., Biasucci L. M., Gallimore J. R., Grillo R. L., Rebuzzi A. G., Pepys M. B., Maseri A. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994 Aug 18;331(7):417–424. doi: 10.1056/NEJM199408183310701. [DOI] [PubMed] [Google Scholar]
  16. McDonagh T. A., Woodward M., Morrison C. E., McMurray J. J., Tunstall-Pedoe H., Lowe G. D., McColl K. E., Dargie H. J. Helicobacter pylori infection and coronary heart disease in the North Glasgow MONICA population. Eur Heart J. 1997 Aug;18(8):1257–1260. doi: 10.1093/oxfordjournals.eurheartj.a015436. [DOI] [PubMed] [Google Scholar]
  17. Mendall M. A., Goggin P. M., Molineaux N., Levy J., Toosy T., Strachan D., Camm A. J., Northfield T. C. Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J. 1994 May;71(5):437–439. doi: 10.1136/hrt.71.5.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mendall M. A., Patel P., Ballam L., Strachan D., Northfield T. C. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996 Apr 27;312(7038):1061–1065. doi: 10.1136/bmj.312.7038.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mickey R. M., Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989 Jan;129(1):125–137. doi: 10.1093/oxfordjournals.aje.a115101. [DOI] [PubMed] [Google Scholar]
  20. Murray L. J., Bamford K. B., O'Reilly D. P., McCrum E. E., Evans A. E. Helicobacter pylori infection: relation with cardiovascular risk factors, ischaemic heart disease, and social class. Br Heart J. 1995 Nov;74(5):497–501. doi: 10.1136/hrt.74.5.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pasceri V., Cammarota G., Patti G., Cuoco L., Gasbarrini A., Grillo R. L., Fedeli G., Gasbarrini G., Maseri A. Association of virulent Helicobacter pylori strains with ischemic heart disease. Circulation. 1998 May 5;97(17):1675–1679. doi: 10.1161/01.cir.97.17.1675. [DOI] [PubMed] [Google Scholar]
  22. Patel P., Carrington D., Strachan D. P., Leatham E., Goggin P., Northfield T. C., Mendall M. A. Fibrinogen: a link between chronic infection and coronary heart disease. Lancet. 1994 Jun 25;343(8913):1634–1635. doi: 10.1016/s0140-6736(94)93084-8. [DOI] [PubMed] [Google Scholar]
  23. Patel P., Mendall M. A., Carrington D., Strachan D. P., Leatham E., Molineaux N., Levy J., Blakeston C., Seymour C. A., Camm A. J. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ. 1995 Sep 16;311(7007):711–714. doi: 10.1136/bmj.311.7007.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peek R. M., Jr, Miller G. G., Tham K. T., Perez-Perez G. I., Zhao X., Atherton J. C., Blaser M. J. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995 Dec;73(6):760–770. [PubMed] [Google Scholar]
  25. Pérez-Pérez G. I., Bhat N., Gaensbauer J., Fraser A., Taylor D. N., Kuipers E. J., Zhang L., You W. C., Blaser M. J. Country-specific constancy by age in cagA+ proportion of Helicobacter pylori infections. Int J Cancer. 1997 Jul 29;72(3):453–456. doi: 10.1002/(sici)1097-0215(19970729)72:3<453::aid-ijc13>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  26. Rathbone B., Martin D., Stephens J., Thompson J. R., Samani N. J. Helicobacter pylori seropositivity in subjects with acute myocardial infarction. Heart. 1996 Oct;76(4):308–311. doi: 10.1136/hrt.76.4.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973–979. doi: 10.1056/NEJM199704033361401. [DOI] [PubMed] [Google Scholar]
  28. Ridker P. M. Inflammation, infection, and cardiovascular risk: how good is the clinical evidence? Circulation. 1998 May 5;97(17):1671–1674. doi: 10.1161/01.cir.97.17.1671. [DOI] [PubMed] [Google Scholar]
  29. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  30. Schembri M. A., Lin S. K., Lambert J. R. Comparison of commercial diagnostic tests for Helicobacter pylori antibodies. J Clin Microbiol. 1993 Oct;31(10):2621–2624. doi: 10.1128/jcm.31.10.2621-2624.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson S. G., Kienast J., Pyke S. D., Haverkate F., van de Loo J. C. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med. 1995 Mar 9;332(10):635–641. doi: 10.1056/NEJM199503093321003. [DOI] [PubMed] [Google Scholar]
  32. Wald N. J., Law M. R., Morris J. K., Bagnall A. M. Helicobacter pylori infection and mortality from ischaemic heart disease: negative result from a large, prospective study. BMJ. 1997 Nov 8;315(7117):1199–1201. doi: 10.1136/bmj.315.7117.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Whincup P. H., Mendall M. A., Perry I. J., Strachan D. P., Walker M. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart. 1996 Jun;75(6):568–572. doi: 10.1136/hrt.75.6.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yamaoka Y., Kita M., Kodama T., Sawai N., Kashima K., Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut. 1997 Oct;41(4):442–451. doi: 10.1136/gut.41.4.442. [DOI] [PMC free article] [PubMed] [Google Scholar]

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