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

BMJ 2000; 321 doi: https://doi.org/10.1136/bmj.321.7255.208 (Published 22 July 2000) Cite this as: BMJ 2000;321:208

Abstract

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 (χ2=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.

Footnotes

    • Accepted 6 June 2000

    Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis

    1. John Danesh, clinical research fellowa,
    2. Peter Whincup, professorb,
    3. Mary Walker, senior lecturerc,
    4. Lucy Lennon, research assistantc,
    5. Andrew Thomson, computer programmerc,
    6. Paul Appleby, statisticiand,
    7. Yuk-ki Wong, research registrare,
    8. Martine Bernardes-Silva, research scientiste,
    9. Michael Ward, professore
    1. a Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX2 6HE
    2. b Department of Public Health Sciences, St George's Hospital Medical School, London SW17 ORE
    3. c Department of Population Sciences and Primary Care, Royal Free and University College London Medical School, London NW3 2PF
    4. d Imperial Cancer Research Fund Cancer Epidemiology Unit, Oxford OX2 6HE
    5. e Departments of Cardiology and Molecular Microbiology, University of Southampton, Southampton SO16 6YD
    6. University of Wales College of Medicine, Cardiff CF4 4XN
    1. Correspondence to: J Danesh
    • Accepted 6 June 2000

    Abstract

    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 (χ2=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.

    Footnotes

    • Funding The British Regional Heart Study is a British Heart Foundation research group and also receives support from the Department of Health. JD was supported by a Merton College fellowship and a Frohlich award.

    • Competing interests None declared.

    • Accepted 6 June 2000

    Commentary: Adjustment for potential confounders may have been taken too far

    1. Robert West, reader in epidemiology
    1. a Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX2 6HE
    2. b Department of Public Health Sciences, St George's Hospital Medical School, London SW17 ORE
    3. c Department of Population Sciences and Primary Care, Royal Free and University College London Medical School, London NW3 2PF
    4. d Imperial Cancer Research Fund Cancer Epidemiology Unit, Oxford OX2 6HE
    5. e Departments of Cardiology and Molecular Microbiology, University of Southampton, Southampton SO16 6YD
    6. University of Wales College of Medicine, Cardiff CF4 4XN

      Footnotes

      • Embedded Image Further details of the meta-analysis are available on the BMJ's website

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