Evidence mapPaperPMID 42334366Full record

ArticleCardiovascular research2026

Associations of the inflammasome-dependent cytokine IL-18 with risk of coronary heart disease.

Harry Björkbacka, Isabel Gonçalves, Gunnar Engström, Alexandru Schiopu, Anna von Sydow, Maria Ryaboshapkina, Vijayalakshmi Varma, Alastair Moss, Angela C Shore, Andrea Natali and 2 more

Abstract readMulticenter Study
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Article in Cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Harry BjörkbackaDepartment of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0003-3918-0857
Isabel GonçalvesDepartment of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0002-2935-0181
Gunnar EngströmDepartment of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0002-8618-9152
Alexandru SchiopuDepartment of Translational Medicine, Lund University, Malmö, Sweden.ORCID 0000-0002-7587-5050
Anna von SydowAstraZeneca, Mölndal, Sweden.
Maria RyaboshapkinaAstraZeneca, Mölndal, Sweden.
Vijayalakshmi VarmaAstraZeneca, Gaithersburg, USA.
Alastair MossAstraZeneca, Cambridge, UK.
Angela C ShoreDiabetes and Vascular Medicine, University of Exeter Medical School and NIHR Exeter Clinical Research Facility, Exeter, UK.
Andrea NataliDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID 0000-0002-8465-7717
Faisel KhanDivision of Cardiovascular Research, University of Dundee, Dundee, UK.ORCID 0000-0002-9889-0229
Jan NilssonDepartment of Clinical Sciences Malmö, Lund University, Sweden.ORCID 0000-0002-9752-7479

Funding

ALFAstraZenecaInnovative Medicines Initiative IMI-2008/115006LeDucq Foundation Network of ExcellenceLund University STYR 2019/2046Lund University Diabetes Centre 2009-1039NIHR Exeter Clinical Research FacilitySkåne University HospitalSUS Foundations and FundsSwedish Foundation for Strategic Research IRC15-006Swedish Heart and Lung foundationSwedish Research Council
6 · The paper itself

Abstract

aimsInflammasome activation has emerged as a promising therapeutic target to reduce residual cardiovascular (CV) risk in patients on guideline lipid-lowering therapy. IL-1β and IL-6 have been intensively studied, whereas the role of the inflammasome-related cytokine IL-18 has gained less attention. Here we aimed to assess the associations of IL-18 with risk of coronary events and severity of atherosclerosis. METHODS AND

resultsThe study included 4742 participants participating in a prospective Swedish Malmö Diet and Cancer (MDC) cohort study, 54 219 general population participants in the UK Biobank, and 1500 participants with Type 2 diabetes and/or known CV disease in the European multicentre SUMMIT VIP imaging study. Plasma levels of IL-18 were analysed using proximity extension assay and atherosclerosis by carotid ultrasound. The incidence of MI and CV death was registered during a 23-year follow-up for the MDC cohort and for a 15-year follow-up for the UK Biobank cohort. There were 617 cases of MI and 644 CV deaths in the MDC cohort and 2454 cases of MI and 1537 CV deaths in the UK Biobank cohort. Elevated IL-18 was associated with an increased risk of MI and CV death independent of hsCRP and IL-6 in both cohorts. In Cox proportional hazards regression models, this association was independent of major CV risk factors in the UK Biobank but not in the MDC cohort. IL-18 did not provide clinically meaningful risk reclassification in the UK Biobank cohort. The association of IL-18 with carotid atherosclerosis in the SUMMIT VIP cohort was weaker than that of IL-6.

conclusionIL-18 is independently associated with risk of MI and CV death in the general population but does not improve clinical risk stratification. Targeting IL-18 directly or through inflammasome inhibition represents a promising approach for treatment of residual inflammatory risk in high-risk atherosclerosis patients that merits to be evaluated in future randomized clinical trials.

Indexed as

Carotid Artery DiseasesCoronary Artery DiseaseInflammasomesInflammation MediatorsInterleukin-18AgedBiomarkersFemaleHeart Disease Risk FactorsHumansIncidenceMaleMiddle AgedMyocardial InfarctionPrognosisProspective StudiesBiomarkersIL18 protein, humanInflammasomesInflammation MediatorsInterleukin-18AtherosclerosisBiomarkersDrug targetsInflammasomeMyocardial infarction

Identifiers

PMID42334366

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.