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

Abstract

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.

Figure 1

Prospective studies of C reactive protein and coronary heart disease. Risk ratios compare top and bottom thirds of baseline measurements. Black squares indicate the risk ratio in each study, with the size of square proportional to number of cases. The combined risk ratio and its 95% confidence interval are indicated by unshaded diamonds for subtotals and shaded diamond for total. All studies adjusted for age, sex, smoking, and some other standard vascular risk factors; the first three studies also adjusted for markers of socioeconomic status

Figure 2

Prospective studies of serum amyloid A protein concentration and coronary heart disease. Risk ratios compare top and bottom thirds of baseline measurements. Black squares indicate the risk ratio in each study, with the size of square proportional to number of cases. All studies adjusted for age, sex, smoking, and some other standard vascular risk factors; our study also adjusted for markers of socioeconomic status