TY - JOUR
T1 - Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts
AU - Herder, Christian
AU - de Las Heras Gala, Tonia
AU - Carstensen-Kirberg, Maren
AU - Huth, Cornelia
AU - Zierer, Astrid
AU - Wahl, Simone
AU - Sudduth-Klinger, Julie
AU - Kuulasmaa, Kari
AU - Peretz, David
AU - Ligthart, Symen
AU - Bongaerts, Brenda W C
AU - Dehghan, Abbas
AU - Ikram, M Arfan
AU - Jula, Antti
AU - Kee, Frank
AU - Pietilä, Arto
AU - Saarela, Olli
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Meisinger, Christa
AU - Peters, Annette
AU - Roden, Michael
AU - Salomaa, Veikko
AU - Koenig, Wolfgang
AU - Thorand, Barbara
N1 - © 2017 American Heart Association, Inc.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Cardiovascular Diseases
KW - Humans
KW - Interleukin 1 Receptor Antagonist Protein
KW - Odds Ratio
KW - Prognosis
KW - Risk Assessment
KW - Risk Factors
KW - Time Factors
KW - Journal Article
KW - Meta-Analysis
KW - Review
U2 - 10.1161/ATVBAHA.117.309307
DO - 10.1161/ATVBAHA.117.309307
M3 - Review article
C2 - 28428221
VL - 37
SP - 1222
EP - 1227
JO - Arteriosclerosis Thrombosis and Vascular Biology
JF - Arteriosclerosis Thrombosis and Vascular Biology
SN - 1079-5642
IS - 6
ER -
