SynthesisLancet (London, England)2012
Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.
Synthesis in Lancet (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 413 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
413 citing papers in PubMed, 8 syntheses or guidelines pooled it, 810 citations in OpenAlex.
- A multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway.Cardiovascular research · 2025Pooled it
- Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.The Cochrane database of systematic reviews · 2024Pooled it
- Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.Journal of interventional cardiology · 2024Pooled it
- The relationship between pre-operative psoas and skeletal muscle parameters and survival following endovascular aneurysm repair: a systematic review and meta-analysis.Scientific reports · 2022Pooled it
- Association of clonal hematopoiesis mutations with clinical outcomes: A systematic review and meta-analysis.American journal of hematology · 2022Pooled it
- Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Gene and Human Diseases and Phenotypes.Frontiers in immunology · 2022Pooled it
- The association of child maltreatment and systemic inflammation in adulthood: A systematic review.PloS one · 2021Pooled it
- Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes.EBioMedicine · 2020Pooled it
- Effect of IL-6 receptor inhibition on infarct volume after endovascular treatment for ischaemic stroke: a phase 2, randomised, placebo-controlled trial.EBioMedicine · 2026Trial
- Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.Cardiovascular research · 2022Trial
- Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial.European heart journal · 2020Trial
- Cardiovascular Disease in CKD: Ethnic and Regional Differences in Risk and Phenotype.Clinical journal of the American Society of Nephrology : CJASN · 2026Review
- Impact of Downregulated Inflammation via the IL6R Asp358Ala Variant on Atrial Fibrillation Recurrence Following Ablation.JACC. Advances · 2026Article
- Red Blood Cell Distribution Width Is a Biomarker of Red Cell Dysfunction Associated with Inflammation, Macrophage Polarization, and Coronary Artery Calcification: A Prognostic Marker in Cardiovascular Disease and a Potential Target for Anti-Cytokine Therapy.Life (Basel, Switzerland) · 2026Review
- Interleukin-6 as an Oral-Vascular Inflammatory Bridge: Integrating CXCL10 and Haptoglobin 2-2 into a Potential Model of Periodontitis-Associated Cardiovascular Risk.International journal of molecular sciences · 2026Review
- Lipoprotein(a), Inflammation, and Risk of Coronary Artery Disease and Aortic Valve Stenosis.JAMA cardiology · 2026Article
- Interplay Between Interleukin-6 Receptor and Lipoprotein(a) in the Causal Association With Cardiovascular Disease.JACC. Basic to translational science · 2026Article
- Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions.JACC. Basic to translational science · 2026Article
- Targeting Inflammation in Atherosclerotic Cardiovascular Disease: Mechanisms and Emerging Therapies.Immunological reviews · 2026Review
- Biomarkers of Cardiovascular Stress: A Historical Review.Journal of cardiovascular development and disease · 2026Review
353 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
97 authors at 20 institutions in 10 countries.
Funding
Abstract
backgroundPersistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling.
methodsIn a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.
findingsThe minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.
interpretationLarge-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
fundingBritish Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.