ArticleBritish journal of clinical pharmacology2022
Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.
Article in British journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Mendelian randomization studies on ischemic stroke: a field synopsis and systematic review.Journal of translational medicine · 2025Pooled it
- Appraising the Causal Role of Risk Factors in Coronary Artery Disease and Stroke: A Systematic Review of Mendelian Randomization Studies.Journal of the American Heart Association · 2023Pooled it
- Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.PLoS medicine · 2023Pooled it
- IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.Nature medicine · 2024Trial
- The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes: The Cross Cohort Collaboration (CCC).Journal of the American College of Cardiology · 2026Observational
- Triglyceride-Rich Lipoproteins and Inflammation: Independent and Synergistic Roles in Cardiovascular Disease.Current atherosclerosis reports · 2026Review
- Remote ischemic preconditioning in elderly patients with acute myocardial infarction and transient ischemic attack: a retrospective cohort study.Frontiers in cardiovascular medicine · 2026Article
- The role of IL-6 in atherosclerosis: a narrative review.Frontiers in cardiovascular medicine · 2026Review
- Autophagy, telomerase, and endothelial dysfunction in COVID-19-induced cardiac injury: an evidence-graded genetic and epigenetic synthesis.Frontiers in cardiovascular medicine · 2026Review
- Obesity-driven low-grade chronic inflammation as a mechanistic bridge to chronic pain: from adipose tissue remodeling to central sensitization.Frontiers in immunology · 2026Review
- C-reactive protein polygenic risk is associated with obesity-related traits in schizophrenia spectrum disorders.Frontiers in psychiatry · 2026Article
- Redefining cardiometabolic biomarkers in the big data era: toward a personalized medicine-centered reconstruction of risk prediction models.Frontiers in cardiovascular medicine · 2026Article
- Triglyceride-glucose index and atherogenic index of plasma as predictors of cardiovascular risk in rectal cancer survivors.Frontiers in cardiovascular medicine · 2026Article
- Shared genetic associations between CHAInternational journal of cardiology. Cardiovascular risk and prevention · 2025Article
- Inflammatory Biomarkers in Heart Failure: Clinical Perspectives on hsCRP, IL-6 and Emerging Candidates.Current heart failure reports · 2025Review
- Thromboelastography and interleukin-6 predict postoperative negative remodeling of descending aorta in patients with type A aortic dissection.Journal of thoracic disease · 2025Article
- IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk.Nature cardiovascular research · 2025Article
- Epigenetic mechanisms underlying variation of IL-6, a well-established inflammation biomarker and risk factor for cardiovascular disease.Atherosclerosis · 2025Article
- Human Genetics Informing Drug Development in Cardiovascular Disease: Interleukin-6 Signaling as a Case Study.Circulation. Genomic and precision medicine · 2025Review
- Correlation Analysis of Gut Microbiota Derivatives with Coronary Artery Disease Severity and Prognosis.Reviews in cardiovascular medicine · 2025Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
aimsChronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.
methodsWe constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.
resultsA 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.
conclusionsIL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.
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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 OpenQuestion graph.