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Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses

BMJ 2000; 321 doi: (Published 22 July 2000) Cite this as: BMJ 2000;321:199
  1. John Danesh, clnical 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. J Ruth Gallimore, research officerc,
  8. Mark B Pepys, professor of medicinec
  1. a Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE
  2. b Department of Public Health Sciences, St George's Hospital Medical School, London SW17 0RE
  3. c Departments of Medicine and Population Sciences and Primary Care, Royal Free and University College Medical School, London NW3 2PF
  4. d Imperial Cancer Research Fund Cancer Epidemiology Unit, Oxford OX2 6HE
  1. Correspondence to: J Danesh
  • Accepted 22 February 2000


Objective: To assess associations between baseline values of four different circulating markers of inflammation and future risk of coronary heart disease, potential triggers of systemic inflammation (such as persistent infection), and other markers of inflammation.

Design: Nested case-control comparisons in a prospective, population based cohort.

Setting: General practices in 18 towns in Britain.

Participants: 506 men who died from coronary heart disease or had a non-fatal myocardial infarction and 1025 men who remained free of such disease until 1996 selected from 5661 men aged 40–59 years who provided blood samples in 1978-1980.

Main outcome measures: Plasma concentrations of C reactive protein, serum amyloid A protein, and serum albumin and leucocyte count. Information on fatal and non-fatal coronary heart disease was obtained from medical records and death certificates.

Results: Compared with men in the bottom third of baseline measurements of C reactive protein, men in the top third had an odds ratio for coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age, town, smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to 1.04) for albumin. No strong associations were observed of these factors with Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma total homocysteine concentrations. Baseline values of the acute phase reactants were significantly associated with one another (P<0.0001), although the association between low serum albumin concentration and leucocyte count was weaker (P=0.08).

Conclusion: In the context of results from other relevant studies these findings suggest that some inflammatory processes, unrelated to the chronic infections studied here, are likely to be involved in coronary heart disease.


  • Funding The British Regional Heart Study is a British Heart Foundation research group and also receives support from the Department of Health. JD is supported by Merton College and the Frohlich Trust. MBP is supported by the UK Medical Research Council.

  • Competing interests None declared.

  • Embedded Image Tables showing distribution of risk factors in the control population are available on the BMJ's website

  • Accepted 22 February 2000
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