Interleukin-6 and incident coronary heart disease: results from the British Women's Heart and Health Study.

INTRODUCTION: Inflammatory mechanisms may play a role in the pathogenesis of atherosclerosis and its complications. Interleukin-6 (IL-6) is an 'upstream' pro-inflammatory cytokine that stimulates hepatocytes to synthesize acute phase response proteins such as C-reactive protein (CRP) and fibrinogen. The purpose of this study was to determine whether IL-6 is associated with incident coronary heart disease (CHD) events independently of established risk factors and to examine its predictive ability for future CHD events. METHODS: Data from the British Women's Heart and Health Study, a prospective cohort of randomly sampled British women 60-79 years old at baseline was used. Three thousand five hundred and eighty-one women had no evidence of coronary heart disease at baseline and were followed up for a median of 4.6 years. Cox proportional hazard models were used to estimate the association of IL-6 with incident CHD. RESULTS: The age-adjusted association of IL-6 with the risk of CHD (hazard ratio, HR per doubling of IL-6=1.26, 95% CI 1.10, 1.43) was attenuated when adjusting for established CHD risk factors (HR per doubling of IL-6=1.13, 95% CI 0.97, 1.31). The main confounders of the association of IL-6 and CHD risk were smoking and forced expiratory volume (FEV(1)). Further attenuation was observed when additional terms for components of the metabolic syndrome were added into the model (HR=1.08, 95% CI 0.93, 1.27). CONCLUSIONS: There was no strong evidence of an association between IL-6 and incident CHD in older British women after controlling for established CHD risk factors. Studies with measures of lung function and socio-economic position are needed to further investigate the role of IL-6 in CHD etiology.