Inflammatory Cytokines and Risk of Coronary Heart Disease: New Prospective Study and Updated Meta-Analysis
Seshasai, Sreenivasa Rao Kondapally
Di, Angelantonio Emanuele
Lowe, Gordon DO
European Heart Journal
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Kaptoge, S., Seshasai, S. R. K., Gao, P., Freitag, D., Butterworth, A., Borglykke, A., Di, A. E., et al. (2013). Inflammatory Cytokines and Risk of Coronary Heart Disease: New Prospective Study and Updated Meta-Analysis. European Heart Journal, 35 578-589. https://doi.org/10.1093/eurheartj/eht367
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. Methods and Results Interleukin-6 (IL-6), interleukin-18 (IL-18), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor–alpha (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 (HR) 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. 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.
Inflammation, CHD, Cytokines, Risk factors, Meta-analysis
This work was supported by a grant from the British Heart Foundation (RG/08/014), the U.K. Medical Research Council, and the U.K. National Institute of Health Research Cambridge Biomedical Research Centre.
British Heart Foundation (RG/08/014/24067)
External DOI: https://doi.org/10.1093/eurheartj/eht367
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246352