Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis

Kaptoge, S. et al. (2014) Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. European Heart Journal, 35(9), pp. 578-589. (doi: 10.1093/eurheartj/eht367)

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Abstract

Aims: Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta-analysis of prospective studies.<p></p> Methods and results: Interleukin-6 (IL-6), IL-18, matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor-α (TNF-α) were measured at baseline in a case-cohort study of 1514 participants and 833 incident CHD events within population-based prospective cohorts at the Danish Research Centre for Prevention and Health. Age- and sex-adjusted hazard ratios (HRs) for CHD per 1-SD higher log-transformed baseline levels were: 1.37 (95% CI: 1.21–1.54) for IL-6, 1.26 (1.11–1.44) for IL-18, 1.30 (1.16–1.46) for MMP-9, 1.01 (0.89–1.15) for sCD40L, and 1.13 (1.01–1.27) for TNF-α. Multivariable adjustment for conventional vascular risk factors attenuated the HRs to: 1.26 (1.08–1.46) for IL-6, 1.12 (0.95–1.31) for IL-18, 1.21 (1.05–1.39) for MMP-9, 0.93 (0.78–1.11) for sCD40L, and 1.14 (1.00–1.31) for TNF-α. In meta-analysis of up to 29 population-based prospective studies, adjusted relative risks for non-fatal MI or CHD death per 1-SD higher levels were: 1.25 (1.19–1.32) for IL-6; 1.13 (1.05–1.20) for IL-18; 1.07 (0.97–1.19) for MMP-9; 1.07 (0.95–1.21) for sCD40L; and 1.17 (1.09–1.25) for TNF-α.<p></p> Conclusions: Several different pro-inflammatory cytokines are each associated with CHD risk independent of conventional risk factors and in an approximately log-linear manner. The findings lend support to the inflammation hypothesis in vascular disease, but further studies are needed to assess causality.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rumley, Dr Ann
Authors: Kaptoge, S., Seshasai, S. R. K., Gao, P., Freitag, D. F., Butterworth, A. S., Borglykke, A., Di Angelantonio, E., Gudnason, V., Rumley, A., Lowe, G. D.O., Jorgensen, T., and Danesh, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
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