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.

, , , , ,
doi.org/10.1161/ATVBAHA.117.309307, hdl.handle.net/1765/108451
Arteriosclerosis, Thrombosis, and Vascular Biology
Erasmus MC: University Medical Center Rotterdam

Herder, C., De Las Heras Gala, T. (Tonia), Carstensen-Kirberg, M. (Maren), Huth, C., Zierer, A. (Astrid), Wahl, S., … Thorand, B. (2017). Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(6), 1222–1227. doi:10.1161/ATVBAHA.117.309307