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

• Published in: European heart journal 2014-03, Vol.35 (9), p.578-589
• Main Authors: Kaptoge, Stephen, Seshasai, Sreenivasa Rao Kondapally, Gao, Pei, Freitag, Daniel F, Butterworth, Adam S, Borglykke, Anders, Di Angelantonio, Emanuele, Gudnason, Vilmundur, Rumley, Ann, Lowe, Gordon D O, Jørgensen, Torben, Danesh, John
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers - metabolism; Clinical Research; Coronary Disease - etiology; Cytokines - metabolism; Female; Humans; Male; Middle Aged; Myocardial Infarction - etiology; Prospective Studies; Risk Factors
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/eht367

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. 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. 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.