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

TitleCirculating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts
Publication TypeJournal Article
Year of Publication2017
AuthorsHerder C., T. Gala deLas Heras, Carstensen-Kirberg M., Huth C., Zierer A., Wahl S., Sudduth-Klinger J., Kuulasmaa K., Peretz D., Ligthart S., Bongaerts B.WC, Dehghan A., Ikram M.A, Jula A., Kee F., Pietila A., Saarela O., Zeller T., Blankenberg S., Meisinger C., Peters A., Roden M., Salomaa V., Koenig W., Thorand B.
JournalArterioscler Thromb Vasc Biol
Volume37
Pagination1222-1227
Date PublishedJun
ISBN Number1079-5642
Accession Number28428221
Keywordsbiomarker, Biomarkers/blood, cardiovascular disease, Cardiovascular Diseases/*blood/diagnosis/*epidemiology, Cohort study, Humans, Inflammation, Interleukin 1 Receptor Antagonist Protein/*blood, interleukin-1 receptor antagonist, meta-analysis, Odds Ratio, Prognosis, Risk Assessment, Risk Factors, Time Factors
Abstract

OBJECTIVE: Interleukin (IL)-1beta represents a key cytokine in the development of cardiovascular disease (CVD). IL-1beta 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.

Short TitleArterioscler. Thromb. Vasc. Biol.Arterioscler. Thromb. Vasc. Biol.
Alternate JournalArteriosclerosis, thrombosis, and vascular biology