Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis
Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis
复制标题
DOI：
10.1093/eurheartj/eht367
复制
发表时间：
2014-03-01
影响因子：
39.3
通讯作者：
Danesh, John
中科院分区：
文献类型：
--
作者：
Kaptoge, Stephen;Seshasai, Sreenivasa Rao Kondapally;Danesh, John
由于低级别炎症可能在冠心病(CHD)的发病机制中起作用，而促炎细胞因子主导炎症级联反应，本研究旨在评估几种促炎细胞因子与冠心病风险的关系，包括前瞻性研究的荟萃分析。在丹麦预防与健康研究中心基于人群的前瞻性队列研究中，对1514名参与者和833起冠心病事件进行了基线测量。年龄和性别调整后的危险比(HR)分别为：IL-6 1.37(95可信区间：1.211.54)、IL-18 1.26(1.111.44)、MMP-9 1.30(1.161.46)、sCD40L 1.01(0.891.15)和TNF-1 1.13(1.011.27)。对常规血管危险因素的多变量调整使HR值降低：IL-6为1.26(1.081.46)，IL-18为1.12(0.951.31)，MMP9为1.21(1.051.39)，sCD40L为0.93(0.781.11)，TNF-α为1.14(1.001.31)。在对29项基于人群的前瞻性研究进行的荟萃分析中，调整后的相对危险度为：IL-6为1.25(1.191.32)，IL-18为1.13(1.051.20)，基质金属蛋白酶-9为1.07(0.971.19)，sCD40L为1.07(0.951.21)，肿瘤坏死因子为1.17(1.091.25)。这些发现支持了血管疾病中的炎症假说，但还需要进一步的研究来评估因果关系。
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- (TNF-) 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: 1.211.54) for IL-6, 1.26 (1.111.44) for IL-18, 1.30 (1.161.46) for MMP-9, 1.01 (0.891.15) for sCD40L, and 1.13 (1.011.27) for TNF-. Multivariable adjustment for conventional vascular risk factors attenuated the HRs to: 1.26 (1.081.46) for IL-6, 1.12 (0.951.31) for IL-18, 1.21 (1.051.39) for MMP-9, 0.93 (0.781.11) for sCD40L, and 1.14 (1.001.31) for TNF-. 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 (1.191.32) for IL-6; 1.13 (1.051.20) for IL-18; 1.07 (0.971.19) for MMP-9; 1.07 (0.951.21) for sCD40L; and 1.17 (1.091.25) for TNF-.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.