Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts

Christian Herder, Tonia de Las Heras Gala, Maren Carstensen-Kirberg, Cornelia Huth, Astrid Zierer, Simone Wahl, Julie Sudduth-Klinger, Kari Kuulasmaa, David Peretz, Symen Ligthart, Brenda W C Bongaerts, Abbas Dehghan, M Arfan Ikram, Antti Jula, Frank Kee, Arto Pietilä, Olli Saarela, Tanja Zeller, Stefan Blankenberg, Christa MeisingerAnnette Peters, Michael Roden, Veikko Salomaa, Wolfgang Koenig, Barbara Thorand

Research output: Contribution to journalReview article

39 Citations (Scopus)

Abstract

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 (I2=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.

Original languageEnglish
Pages (from-to)1222-1227
Number of pages6
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume37
Issue number6
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Biomarkers
  • Cardiovascular Diseases
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Odds Ratio
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Journal Article
  • Meta-Analysis
  • Review

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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., 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., ... Thorand, B. (2017). Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts. Arteriosclerosis Thrombosis and Vascular Biology, 37(6), 1222-1227. https://doi.org/10.1161/ATVBAHA.117.309307