Interleukin-6 and incident coronary heart disease: results from the British Women's Heart and Health Study.
BACKGROUND
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.
Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. Abigail.fraser@bristol.ac.uk
Abigail
A
Fraser
Margaret
M
May
Gordon
G
Lowe
Ann
A
Rumley
George Davey
GD
Smith
Shah
S
Ebrahim
Debbie A
DA
Lawlor
D000368:Aged; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D016387:Women's Health
C508600:IL6 protein, human; D015850:Interleukin-6