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 Meisinger; Annette Peters; Michael Roden; Veikko Salomaa; Wolfgang Koenig; Barbara Thorand

doi:10.1161/ATVBAHA.117.309307

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 journal › Review article › peer-review

44 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 language	English
Pages (from-to)	1222-1227
Number of pages	6
Journal	Arteriosclerosis Thrombosis and Vascular Biology
Volume	37
Issue number	6
DOIs	https://doi.org/10.1161/ATVBAHA.117.309307
Publication status	Published - 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

Herder, Christian ; de Las Heras Gala, Tonia ; Carstensen-Kirberg, Maren ; Huth, Cornelia ; Zierer, Astrid ; Wahl, Simone ; Sudduth-Klinger, Julie ; Kuulasmaa, Kari ; Peretz, David ; Ligthart, Symen ; Bongaerts, Brenda W C ; Dehghan, Abbas ; Ikram, M Arfan ; Jula, Antti ; Kee, Frank ; Pietilä, Arto ; Saarela, Olli ; Zeller, Tanja ; Blankenberg, Stefan ; Meisinger, Christa ; Peters, Annette ; Roden, Michael ; Salomaa, Veikko ; Koenig, Wolfgang ; Thorand, Barbara. / Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts. In: Arteriosclerosis Thrombosis and Vascular Biology. 2017 ; Vol. 37, No. 6. pp. 1222-1227.

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

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.",

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

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

note = "{\textcopyright} 2017 American Heart Association, Inc.",

year = "2017",

month = jun,

doi = "10.1161/ATVBAHA.117.309307",

language = "English",

volume = "37",

pages = "1222--1227",

journal = "Arteriosclerosis Thrombosis and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "6",

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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, BWC, Dehghan, A, Ikram, MA, Jula, A, Kee, F, Pietilä, A, Saarela, O, Zeller, T, Blankenberg, S, Meisinger, C, Peters, A, Roden, M, Salomaa, V, Koenig, W & 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, vol. 37, no. 6, pp. 1222-1227. https://doi.org/10.1161/ATVBAHA.117.309307

Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts. / Herder, Christian; de Las Heras Gala, Tonia; Carstensen-Kirberg, Maren; Huth, Cornelia; Zierer, Astrid; Wahl, Simone; Sudduth-Klinger, Julie; Kuulasmaa, Kari; Peretz, David; Ligthart, Symen; Bongaerts, Brenda W C; Dehghan, Abbas; Ikram, M Arfan; Jula, Antti; Kee, Frank; Pietilä, Arto; Saarela, Olli; Zeller, Tanja; Blankenberg, Stefan; Meisinger, Christa; Peters, Annette; Roden, Michael; Salomaa, Veikko; Koenig, Wolfgang; Thorand, Barbara.

In: Arteriosclerosis Thrombosis and Vascular Biology, Vol. 37, No. 6, 06.2017, p. 1222-1227.

Research output: Contribution to journal › Review article › peer-review

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

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 -