Objective-To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease.Design-Population based cross sectional study. Setting-General practices in Merton, Sutton, andWandsworth.Subjects-A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined.Interventions-Measurements ofserum C reactive protein concentrations by in house enzyme linked inmunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms.Main outcome measures-Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease.Results-Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamrydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease.

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Objective-To determine whether serum concentrations of the cytokines tumour necrosis factor a (TNFa) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. Design--A population based cross sectional study. Subjects and methods-198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. Results-Serum TNFa concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNFa was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNFa, each by approximately 50% (P < 0*05 for TNFa, P < 0 1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNFa and 36% for IL-6 (P = 0*14 for TNFa and P < 0*05 for IL-6). Conclusions-This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism. (Heart 1997;78:273-277) Keywords: C reactive protein; interleukin 6; TNFa; cardiovascular risk; coronary heart disease Cardiovascular risk factors as established in prospective studies could be considered to fall into two broad groups: endogenous and exogenous (lifestyle) Inflammation may be this mechanism.Most cardiovascular risk factors are changed in an adverse direction by acute inflammation: fibrinogen and the white blood cell count rise, glucose rises, HDL falls, and triglycerides rise.5-7 We have shown recently that low levels of systemic inflammation, as measured by serum C reactive protein in normal subjects, are related to many of these endogenous risk factors and that these levels of inflammatory activity are influenced in turn by many of the exogenous (lifestyle) cardiovascular risk factors.8 C reactive protein production by the liver is regulated by cytokines, principally interleukin 6 (IL-6), and tumour necrosis factor a (TNFa), which is the main trigger for the production of IL-6 by a variety of cells.9 The effect of these cytokines is modulated by cortisol and growth factors such as insulin.'0 In vitro and animal challenge experiments suggest that IL-6 and TNFa play important roles in the regulation of the synthesis of other acute phase proteins which are established risk factors for atherosclerosis, such as fibrinogen and factor VIII.10 These cytokines also have profound effects on lipid meta...

C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.