Ischaemic heart disease and Cag A strains of Helicobacter pylori in the Caerphilly heart disease study.

Abstract

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.

(Heart 2001;86:506-509)

Keywords: ischaemic heart disease; epidemiology; infection; Helicobacter pylori

Helicobacter pylori is a lifelong bacterial infection of the stomach that is mainly acquired in childhood. [1] Over 20 epidemiological studies have been reported that have investigated the role of H pylori in the aetiology of ischaemic heart disease. [2] Early case-control studies [3] 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). [4]

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. [5]

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. [6] 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 …