Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly prospective heart disease study • Commentary: Chlamydia pneumoniae infection and ischaemic heart disease

BMJ 1999;318:1035-1040 ( 17 April )

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Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly prospective heart disease study

David P Strachan, professor, ^a David Carrington, senior lecturer, ^b Michael A Mendall, senior lecturer, ^c Lydia Ballam, research assistant, ^c Julia Morris, research assistant, ^c Barbara K Butland, lecturer, ^a Peter M Sweetnam, statistician, ^d Peter C Elwood, director. ^d

^a Department of Public Health Sciences, St George's Hospital Medical School, London SW17 0RE, ^b Department of Medical Microbiology, St George's Hospital Medical School, ^c Division of Gastroenterology, Endocrinology and Metabolism, St George's Hospital Medical School, ^d Medical Research Council Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan CF64 2XW

Correspondence to: Professor Strachan d.strachan{at}sghms.ac.uk

Objectives: To investigate the effect of Chlamydia pneumoniaeinfection on future development of ischaemic heart disease andmortality.
Design: Prospective longitudinalstudy.
Setting: Caerphilly, SouthWales.
Subjects: Plasma specimens were collected during 1979-83from 1773 men aged 45-59 years. These were tested for IgG andIgA antibodies to C pneumoniae (TW183) bymicroimmunofluorescence.
Outcome measures: 13 year mortality and incident ischaemic heartdisease events were ascertained from death certificates, hospitalrecords, and electrocardiographic changes at follow up every 4to 5years.
Results: 642 men (36.2%) had IgG antibodies at a titreof $>=$ 1 in 16, of whom 362 (20.4% of all men) also had detectableIgA antibodies. The prevalence of ischaemic heart disease (a historyof past or current disease) at entry was similar at all IgG antibodytitres but was positively related to IgA antibody titre. IgA antibodytitre was positively correlated with plasma viscosity but notwith other cardiovascular risk factors. Incidence of ischaemicheart disease was not associated with either IgG antibody titreor IgA antibody titre, but there were stronger and significantrelations of IgA antibodies with all cause mortality and fatalischaemic heart disease, which persisted after adjustment forconventional cardiovascular risk factors. The odds ratios associatedwith detectable IgA antibodies were 1.07 (95% confidence interval0.75 to 1.53) for all incident ischaemic heart disease, 1.83 (1.17to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to2.04) for all causemortality.
Conclusion: This is the first prospective demonstrationof an association between IgA antibodies to C pneumoniae, a putativemarker of chronic infection, and subsequent risk of death fromischaemic heart disease. In contrast to earlier case-control studies,IgG antibodies were not associated with either prevalent or incidentischaemic heartdisease.

Key messages

Middle aged men with circulating IgA antibodies against Chlamydia pneumoniae had increased mortality over a 13 year period, mainly due to an excess of fatal ischaemic heart disease
This association was largely independent of conventional cardiovascular risk factors and attributable to increased case fatality of ischaemic heart disease among men with detectable IgA antibodies
No association was found between C pneumoniae IgA antibody titre and incident ischaemic heart disease (fatal and non-fatal combined), nor between C pneumoniae IgG antibody titre and incident ischaemic heart disease
This is the first study to suggest an association between persistent C pneumoniae infection and subsequent mortality

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