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Objective--To look for the presence of the more virulent strains of Helicobacter pylori (H pylori) in men who developed ischaemic heart disease over a 10 year period and in controls.
Design--The Caerphilly prospective heart disease study recruited 2512 men aged 45-59 years during 1979-83. Western blot analysis or enzyme linked immunosorbent assay (ELISA) was performed on serum taken from those who subsequently died of ischaemic heart disease, or developed non-fatal myocardial infarction, to determine H pylori and Cag A status. Similar information was available on age matched controls.
Results--During the first decade of the study, 312 men died of ischaemic heart disease or developed non-fatal myocardial infarction. Serum was available from 172 of these (55%). There was no evidence of an association between Cag A seropositivity and incident ischaemic heart disease or ischaemic heart disease mortality, either before or after adjustment for potential confounders (adjusted odds ratios 1.18 (95% confidence interval (CI) 0.76 to 1.85) and 1.13 (95% CI 0.61 to 2.07), respectively). Further, the odds ratios for ischaemic heart disease incidence and ischaemic heart disease mortality by H pylori seropositivity did not appear to depend on the presence or absence of Cag A strains (p = 0.76 and 0.77, respectively).
Conclusions--In this cohort of middle aged men, followed over a 10 year period, there is little evidence of an association between Cag A seropositivity and either incident ischaemic heart disease or ischaemic heart disease mortality.
Keywords: ischaemic heart disease; epidemiology; infection; Helicobacter pylori
Helicobacter pylori is a lifelong bacterial infection of the stomach that is mainly acquired in childhood.  Over 20 epidemiological studies have been reported that have investigated the role of H pylori in the aetiology of ischaemic heart disease.  Early case-control studies  broadly supported an association. Cross sectional population studies have given more mixed findings, while more detailed information has recently come from large population based prospective case-control studies. These have attempted to overcome the bias present in case-control and cross sectional studies, and are consistent with only very modest effects. A meta-analysis performed on the seven previous prospective studies involving H pylori and ischaemic heart disease covered 2286 cases. A combined analysis showed an adjusted odds ratio of 1.16 (95% confidence interval (CI) 0.94 to 1.43). 
The inconsistent results may stem from the fact that bacterial and host factors influence the risk, and these have not been assessed in the studies to date. There is a great variability in the severity of H pylori associated gastritis, both between individuals and also at varying stages of life within the individual. Gastritis is more severe in young and early middle aged people, and H pylori may be a stronger risk factor for ischaemic heart disease in younger subjects. 
The H pylori cytotoxin associated gene product A (Cag A) is a marker for enhanced virulence and increased cytotoxin production, and is more commonly found in strains of H pylori causing more severe gastritis, peptic ulcer disease, and gastric cancer.  There are conflicting results from studies designed to investigate the link between CagA seropositivity and ischaemic heart disease, but the results are consistent with a weak association. If confirmed, the finding of a "dose-response" relation between H pylori and ischaemic heart disease would …