SynthesisNeurology2022
Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies.
Open access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph
Synthesis in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
4.8field-weighted citation impact, top 4% of its field
What it found
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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
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Immunosenescence and its impact on ischemic stroke risk and outcomes in older adults: a systematic review.Frontiers in aging neuroscience · 2026Pooled it
- Efficacy and safety of Shenmai injection for acute ischemic stroke: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Targeting interleukin-6 trans-signaling to improve post-stroke inflammation: A precision immunotherapy perspective.Neural regeneration research · 2026Article
- Multimodal profiling of atherosclerosis: Protocol and pilot data for the AtherOMICS biobank.Science advances · 2026Article
- Towards a Compositional Framework for Describing Human Phenotypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Clonal Hematopoiesis and Risk of Stroke: Evidence From Over 800 000 Individuals Across 3 Cohorts.Stroke · 2026Article
- Peripheral inhibition of IL-6 signaling with tocilizumab improves stroke outcomes in aged mice but requires sex-specific dosing.bioRxiv : the preprint server for biology · 2026Article
- Evaluating tocilizumab in ischemic stroke: Findings from the SPAN multicenter trial.Neuropharmacology · 2026Article
- Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review).Molecular medicine reports · 2026Review
- Premature aging in serious mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction.Current atherosclerosis reports · 2026Review
- Beyond Reperfusion: Adjunctive Therapies Targeting Inflammation, Edema, and Blood-Brain Barrier Dysfunction in Ischemic Stroke.Cerebrovascular diseases (Basel, Switzerland) · 2026Review
- A Review of Emerging Biomarkers Connecting Diabetes and Ischemic Stroke: Implications for Early Detection and Risk Stratification.Journal of diabetes research · 2026Review
- Cellular Communication Networks Mediated by Microglia in Ischemic Stroke.CNS neuroscience & therapeutics · 2025Review
- Association between Serum Levels of Interleukin-6 and Stroke, Cardiovascular Events, and Alzheimer's Disease Dementia.Journal of atherosclerosis and thrombosis · 2025Observational
- Reduced interleukin-6 stress reactivity in male physicians with occupational burnout.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Uric Acid to Platelet Ratio (UAPR) and Its Link to Lipid Abnormalities: Findings from a Large Cohort Study in Saudi Arabia.Journal of clinical medicine · 2025Article
- Immunological and Inflammatory Biomarkers in the Prognosis, Prevention, and Treatment of Ischemic Stroke: A Review of a Decade of Advancement.International journal of molecular sciences · 2025Review
- Human Genetics Informing Drug Development in Cardiovascular Disease: Interleukin-6 Signaling as a Case Study.Circulation. Genomic and precision medicine · 2025Review
- Engineered Exosome-Based Senolytic Therapy Alleviates Stroke by Targeting p21Exploration (Beijing, China) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Andreas PapadopoulosFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Konstantinos PalaiopanosFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Harry BjörkbackaFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Annette PetersFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
James A de LemosFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Sudha SeshadriFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Martin DichgansFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
Marios K GeorgakisFrom the Department of Radiology (A.P.), 401 General Military Hospital of Athens; National Public Health Organization (K.P.), Athens, Greece; Department of Clinical Sciences Malmö (H.B.), Lund University, Sweden; Institute of Epidemiology (A.P.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg; German Center for Diabetes Research (DZD) (A.P.), München-Neuherberg, Neuherberg; German Research Center for Cardiovascular Disease (DZHK) (A.P.), Partner Site Munich Heart Alliance; Institute of Medical Information Sciences, Biometry and Epidemiology (A.P.), and Institute for Stroke and Dementia Research, University Hospital (M.D., M.K.G.), Ludwig-Maximilians-University, Munich, Germany; Division of Cardiology (J.A.d.L.), University of Texas Southwestern Medical Center, Dallas; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study (S.S.), Framingham; Department of Medicine (S.S.), Boston University School of Medicine, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (S.S.), University of Texas Health Sciences Center, San Antonio; Munich Cluster for Systems Neurology (SyNergy) (M.D.); and German Centre for Neurodegenerative Diseases (DZNE) (M.D.), Munich, Germany. M.K.G. is currently at the Center for Genomic Medicine, Massachusetts General Hospital, Boston and the Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA. marios.georgakis@med.uni-muenchen.de.
Helmholtz Zentrum München · DE
Funding
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9MNHLBI NIH HHS HHSN268201500001ININDS NIH HHS R01 NS017950
Abstract
BACKGROUND AND
objectivesHuman genetic studies support a key role of interleukin-6 (IL-6) in the pathogenesis of ischemic stroke. However, there are only limited data from observational studies exploring circulating IL-6 levels as a risk factor for ischemic stroke. We set out to perform a systematic review and meta-analysis of aggregate data on cohort studies to determine the magnitude and shape of the association between circulating IL-6 levels and risk of incident ischemic stroke in the general population.
methodsFollowing the PRISMA guidelines, we systematically screened the PubMed search engine from inception to March 2021 for population-based prospective cohort studies exploring the association between circulating IL-6 levels and risk of incident ischemic stroke. We pooled association estimates for ischemic stroke risk with random-effects models and explored nonlinear effects in dose-response meta-analyses. Risk of bias was assessed with the Newcastle-Ottawa Scale (NOS). We used funnel plots and trim-to-fill analyses to assess publication bias.
resultsWe identified 11 studies (n = 27,411 individuals; 2,669 stroke events) meeting our eligibility criteria. Mean age of all included participants was 60.5 years and 54.8% were female. Overall, quality of the included studies was high (median 8 out of 9 NOS points, interquartile range 7-9). In meta-analyses, 1 SD increment in circulating log-transformed IL-6 levels was associated with a 19% increase in risk of incident ischemic stroke over a mean follow-up of 12.4 years (relative risk 1.19; 95% confidence interval 1.10 to 1.28). A dose-response meta-analysis showed a linear association between circulating IL-6 levels and ischemic stroke risk. There was only moderate heterogeneity and the results were consistent in sensitivity analyses restricted to studies of low risk of bias and studies fully adjusting for demographic and vascular risk factors. The results also remained stable following adjustment for publication bias. DISCUSSION: Higher circulating IL-6 levels in community-dwelling individuals are associated with higher long-term risk of incident ischemic stroke in a linear pattern and independently of conventional vascular risk factors. Along with findings from genetic studies and clinical trials, these results provide additional support for a key role of IL-6 signaling in ischemic stroke.
Indexed as
Interleukin-6Ischemic StrokeFemaleHumansMaleMiddle AgedProspective StudiesRisk FactorsInterleukin-6
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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.