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Introduction
Mendall et al showed an association between Helicobacter pylori infection of the stomach and ischaemic heart disease in 1994-5,[1, 2] and 18 studies have reported on the relationship over the subsequent two years.[3-20] The position remains uncertain, an assessment supported by a recent review.[21] Since the risk of acquiring H pylori infection in childhood increases with socioeconomic deprivation and overcrowding,[3, 22] the association may be indirect, H pylori infection and ischaemic heart disease are both related to social class Some studies have shown little or no excess risk,[4-9] but others reported a fourfold to fivefold increased risk without adjustment for measures of social class and other risk factors for ischaemic heart diseases[10-11] or a twofold to threefold increased risk after such adjustment.[1-3]
We report the results of an investigation using a prospective study of the determinants of major chronic disease. This study is well suited to determine whether there is an independent relationship between H pylori infection and ischaemic heart disease. With 648 deaths from ischaemic heart disease it is much the largest study to report on the association. The likelihood of an indirect association arising through social class differences is minimised by the homogeneity of the study population: the subjects were all professional men attending for a routine medical examination. Random error and systematic error are therefore likely to be small.
Methods
The British United Provident (BUPA) study is a prospective study of 21 520 professional men aged 35-64 who attended the BUPA medical centre in London between 1975 and 1982 for a routine medical examination. Serum cholesterol concentration and other risk factors for ischaemic heart disease were measured[23, 24] and serum samples were stored at 40 Celsius The cohort consisted of men resident in Britain, so all records could be flagged at the NHS central register in Southport, permitting automatic notification of death (with the certified cause) and cancer incidence by the Office of Population Censuses and Surveys (now the Office for National Statistics). Further information on the causes of death was obtained by writing to each certifying doctor.
This analysis is based on follow up to the end of December 1994; the average follow up was 15.6 years. In this period 648 men died from ischaemic heart disease (international classification of diseases, 9th revision, codes 410-414) but had no history of ischaemic heart disease on entry. For each case, two controls (who did not die of ischaemic heart disease and did not have a history of ischaemic heart disease on entry) were selected; they were matched for age and duration of storage of the serum sample, each to one year.
In 1997 the frozen serum samples were retrieved. IgG antibody titres specific to H pylori were measured with an enzyme linked …