白细胞介素-1受体拮抗剂的循环水平与心血管疾病风险：六项基于人群队列的荟萃分析
Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts.
作者信息
Herder Christian, de Las Heras Gala Tonia, Carstensen-Kirberg Maren, Huth Cornelia, Zierer Astrid, Wahl Simone, Sudduth-Klinger Julie, Kuulasmaa Kari, Peretz David, Ligthart Symen, Bongaerts Brenda W C, Dehghan Abbas, Ikram M Arfan, Jula Antti, Kee Frank, Pietilä Arto, Saarela Olli, Zeller Tanja, Blankenberg Stefan, Meisinger Christa, Peters Annette, Roden Michael, Salomaa Veikko, Koenig Wolfgang, Thorand Barbara
机构信息
From the Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany (C. Herder, M.C.-K., M.R.); German Center for Diabetes Research (DZD), München-Neuherberg, Germany (C. Herder, M.C.-K., A. Peters, M.R., B.T.); Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.d.l.H.G., C. Huth, A.Z., S.W., C.M., A. Peters, B.T.); German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Germany (T.d.l.H.G., W.K.); Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (S.W.); Tethys Bioscience, Emeryville, CA (J.S.-K., D.P.); National Institute for Health and Welfare, Helsinki, Finland (K.K., A. Pietilä, V.S.); Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands (S.L., A.D., M.A.I.); Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany (B.W.C.B.); Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, United Kingdom (A.D.); National Institute for Health and Welfare, Turku, Finland (A.J.); Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Institute of Clinical Science B, Queen's University Belfast, United Kingdom (F.K.); UKCRC Centre of Excellence for Public Health (Northern Ireland), Queen's University Belfast, United Kingdom (F.K.); Dalla Lana School of Public Health, University of Toronto, Ontario, Canada (O.S.); Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Germany (T.Z., S.B.); German Center for Cardiovascular Research (DZHK), Partner site Hamburg, Lübeck, Kiel, Germany (T.Z., S.B.); Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Germany (M.R.); Deutsches Herzzentrum München, Technische Universität München, Germany (W.K.); and Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Germany (W.K.).
出版信息
Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1222-1227. doi: 10.1161/ATVBAHA.117.309307. Epub 2017 Apr 20.
OBJECTIVE
Interleukin (IL)-1β represents a key cytokine in the development of cardiovascular disease (CVD). IL-1β is counter-regulated by IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor. This study aimed to identify population-based studies on circulating IL-1RA and incident CVD in a systematic review, estimate the association between IL-1RA and incident CVD in a meta-analysis, and to test whether the association between IL-1RA and incident CVD is explained by other inflammation-related biomarkers in the MONICA/KORA Augsburg case-cohort study (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg).
APPROACH AND RESULTS
We performed a systematic literature search and identified 5 cohort studies on IL-1RA and incident CVD in addition to the MONICA/KORA Augsburg case-cohort study for a meta-analysis based on a total of 1855 CVD cases and 18 745 noncases with follow-up times between 5 and 16 years. The pooled standardized hazard ratio (95% confidence interval) for incident CVD was 1.11 (1.06-1.17) after adjustment for age, sex, anthropometric, metabolic, and lifestyle factors (<0.0001). There was no heterogeneity in effect sizes (I=0%; =0.88). More detailed analyses in the MONICA/KORA study showed that the excess risk for CVD was attenuated by ≥10% after additional separate adjustment for serum levels of high-sensitivity C-reactive protein, IL-6, myeloperoxidase, soluble E-selectin, or soluble intercellular adhesion molecule-1.
CONCLUSIONS
Serum IL-1RA levels were positively associated with risk of CVD after adjustment for multiple confounders in a meta-analysis of 6 population-based cohorts. This association may at least partially reflect a response to triggers inducing subclinical inflammation, oxidative stress, and endothelial activation.
目的
白细胞介素（IL）-1β是心血管疾病（CVD）发生发展中的关键细胞因子。IL-1β受内源性抑制剂IL-1受体拮抗剂（IL-1RA）的反向调节。本研究旨在通过系统评价确定关于循环IL-1RA与CVD发病的基于人群的研究，通过荟萃分析估计IL-1RA与CVD发病之间的关联，并在慕尼黑/奥格斯堡地区心血管疾病趋势和决定因素多国监测/合作健康研究（MONICA/KORA奥格斯堡病例队列研究）中检验IL-1RA与CVD发病之间的关联是否可由其他炎症相关生物标志物解释。
方法与结果
我们进行了系统的文献检索，除MONICA/KORA奥格斯堡病例队列研究外，还确定了5项关于IL-1RA与CVD发病的队列研究，用于荟萃分析，共有1855例CVD病例和18745例非病例，随访时间为5至16年。在对年龄、性别、人体测量、代谢和生活方式因素进行调整后，CVD发病的合并标准化风险比（95%置信区间）为1.11（1.06 - 1.17）（<0.0001）。效应大小无异质性（I² = 0%；P = 0.88）。MONICA/KORA研究中更详细的分析表明，在对高敏C反应蛋白、IL-6、髓过氧化物酶、可溶性E选择素或可溶性细胞间黏附分子-1的血清水平进行额外单独调整后，CVD的额外风险降低了≥10%。
结论
在对6项基于人群的队列进行荟萃分析时，调整多个混杂因素后，血清IL-1RA水平与CVD风险呈正相关。这种关联可能至少部分反映了对诱导亚临床炎症、氧化应激和内皮激活的触发因素的反应。
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