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Herder, C.* ; de Las Heras Gala, T. ; Carstensen-Kirberg, M.* ; Huth, C. ; Zierer, A. ; Wahl, S. ; Sudduth-Klinger, J.* ; Kuulasmaa, K.A. ; Peretz, D.* ; Ligthart, S. ; Bongaerts, B.W.C.* ; Dehghan, A.* ; Ikram, M.A. ; Jula, A.* ; Kee, F.* ; Pietilä, A.* ; Saarela, O.* ; Zeller, T.* ; Blankenberg, S.* ; Meisinger, C. ; Peters, A. ; Roden, M.* ; Salomaa, V.* ; Koenig, W.* ; Thorand, B.

Circulating levels of interleukin 1-receptor antagonist and risk of  cardiovascular disease: Meta-analysis of six population-based cohorts.

Arterioscler. Thromb. Vasc. Biol. 37, 1222-1227 (2017)
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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 (P<0.0001). There was no heterogeneity in effect sizes (I(2)=0%; P=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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biomarker ; Cardiovascular Disease ; Cohort Study ; Inflammation ; Interleukin-1 Receptor Antagonist ; Meta-analysis
ISSN (print) / ISBN 1079-5642
e-ISSN 1524-4636
Quellenangaben Volume: 37, Issue: 6, Pages: 1222-1227 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Reviewing status Peer reviewed