Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study.

Abstract

Objective To determine whether there is an independent association between infection with Chlamydia pneumoniae and ischaemic heart disease.

Design Prospective study using a nested case-control design.

Setting Medical centre in London run by BUPA, a private medical organisation.

Participants 21 520 professional men aged 35-64 who attended for a medical examination in London between 1975 and 1982.

Main outcome measure Death from ischaemic heart disease.

Results The distributions of concentrations of IgG and IgA antibodies to C pneumoniae were similar in the 647 men who subsequently died of ischaemic heart disease and in 1294 age matched controls who did not. There was no material association with heart disease irrespective of the cut-off point chosen to define seropositivity. At a cut-off point that defines 15% of controls as positive, for example, the odds ratios were 1.26 (95% confidence interval 0.95 to 1.68) for IgG and 1.09 (0.82 to 1.43) for IgA.

Conclusions No material association was found between infection with C pneumoniae and ischaemic heart disease. The size and prospective design of the study and the socioeconomic homogeneity of the cohort minimise both random and systematic error.

Introduction

Several reports have linked ischaemic heart disease with various infections, notably those caused by Helicobacter pylori and Chlamydia pneumoniae (also called Chlamydophila pneumoniae)[1 2] A review in 1997 emphasised the problems in interpreting these associations.[2] The studies showing associations tended to be small, retrospective, and susceptible to bias or confounding. It was concluded that large prospective studies of socially homogeneous cohorts were needed to resolve the issue[2] We then reported a clearly negative result in much the largest study to report on the association between H pylori and ischaemic heart disease, with 648 deaths.[3] The prospective design of this study reduced bias, and the likelihood of an indirect association arising through differences in social class (socioeconomically disadvantaged people being more likely to have the infection and to develop heart disease regardless of a possible causal link between the two) was minimised by the homogeneity of the study population; the participants were all professional men attending for a routine medical examination. Both random and systematic errors were therefore likely to be small.

The studies of C pneumoniae and heart disease have generated mixed results regardless of whether IgG or IgA was measured.[1 2 4-11] For example, results from the Caerphilly prospective study were negative for IgG antibodies to chlamydia but suggested an association with IgA (odds ratio for fatal ischaemic heart disease 1.83, 95% confidence interval 1.17 to 2.85).[7] We report on the relation between ischaemic heart disease and both IgG and IgA antibodies to C pneumoniae in the BUPA study.

Participants and methods

The study design was as reported previously for H pylori and ischaemic heart disease.[3] Briefly, the BUPA study is a prospective (cohort) study of 21 520 healthy professional men aged 35-64 who attended the BUPA (a private medical organisation) centre in London for a routine medical examination between 1975 and 1982. Risk factors for ischaemic heart disease were measured, and serum samples were stored at -40 [degrees] C. At the end of 1994 (average follow up 15.6 years), 648 men with no history of heart …