Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis Commentary: Adjustment for potential confounders may have been taken too far

OBJECTIVE: To examine the association between coronary heart disease and serum markers of chronic Chlamydia pneumoniae infection. DESIGN: "Nested" case-control analysis in a prospective cohort study and an updated meta-analysis of previous relevant studies. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: Of the 5661 men aged 40-59 who provided blood samples during 1978-80, 496 men who died from coronary heart disease or had non-fatal myocardial infarction and 989 men who had not developed coronary heart disease by 1996 were included. MAIN OUTCOME MEASURES: IgG serum antibodies to C pneumoniae in baseline samples; details of fatal and non-fatal coronary heart disease from medical records and death certificates. RESULTS: 200 (40%) of the 496 men with coronary heart disease were in the top third of C pneumoniae titres compared with 329 (33%) of the 989 controls. The corresponding odds ratio for coronary heart disease was 1.66 (95% confidence interval 1.25 to 2.21), which fell to 1.22 (0.82 to 1.82) after adjustment for smoking and indicators of socioeconomic status. No strong associations were observed between C pneumoniae IgG titres and blood lipid concentrations, blood pressure, or plasma homocysteine concentration. In aggregate, the present study and 14 other prospective studies of C pneumoniae IgG titres included 3169 cases, yielding a combined odds ratio of 1. 15 (0.97 to 1.36), with no significant heterogeneity among the separate studies (chi(2)=10.5, df=14; P>0.1). CONCLUSION: This study, together with a meta-analysis of previous prospective studies, reliably excludes the existence of any strong association between C pneumoniae IgG titres and incident coronary heart disease. Further studies are required, however, to confirm or refute any modest association that may exist, particularly at younger ages.