Evidence map›Paper›PMID 42201287›Full record

Observational studyJournal of the American College of Cardiology2026

The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes: The Cross Cohort Collaboration (CCC).

Zhiqi Yao, Zeina A Dardari, Michael J LaMonte, Kunihiro Matsushita, Christie M Ballantyne, Joao A Lima, Ramachandran S Vasan, Eleanor M Simonsick, Lawrence J Appel, Debbie L Cohen and 16 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of the American College of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. The role of IL-6 in atherosclerosis: a narrative review.Frontiers in cardiovascular medicine · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Zhiqi YaoJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA.
Zeina A DardariJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA.
Michael J LaMonteDepartment of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
Kunihiro MatsushitaJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA; Department of Epidemiology, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Christie M BallantyneDepartment of Medicine, Baylor College of Medicine, and the Texas Heart Institute, Houston, Texas, USA.
Joao A LimaDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Ramachandran S VasanUniversity of Texas School of Public Health, San Antonio, Texas, USA.
Eleanor M SimonsickIntramural Research Program, National Institute on Aging, Baltimore, Maryland, USA.
Lawrence J AppelDepartment of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
Debbie L CohenRenal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Suzanne JuddDepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Peggy M CawthonCalifornia Pacific Medical Center Research Institute, San Francisco, California, USA.
Amil M ShahDivision of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Brittany N WeberDivision of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Tianyu CaoJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York, USA.
Omar DzayeJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA; Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Erfan TasdighiJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA.
Yara JelwanJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA.
Kunal K JhaJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA.
Joshua C BisCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA.
Nels C OlsonDepartment of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, USA.
James P LashDivision of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA.
Mary CushmanDepartment of Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.
Charles B EatonDepartment of Family Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA.
Michael J BlahaJohns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA. Electronic address: mblaha1@jhmi.edu.

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Scientific and Data Coordinating Center(SDCC) for the P*U01DK060990 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI FELDMAN, HAROLD I · 2001 to 2017
$50.1M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Tulane COBRE in Cardiometabolic Diseases Clinical Research CoreP20GM109036 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI Tanika Nicole Kelly · 2016 to 2026
$25.3M
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6 · The paper itself

Abstract

backgroundInterleukin (IL)-6 has emerged as a promising target for cardiovascular disease (CVD) prevention. Better understanding IL-6's contribution to CVD events in community-based, diverse cohorts and in clinically relevant subgroups will provide critical context about IL-6 inhibition for CVD prevention.

objectivesThe aim of this study was to evaluate the association of circulating IL-6 concentrations with incident cardiovascular events and mortality using pooled data from large multiethnic prospective cohorts.

methodsThe authors harmonized individual-level participant data from 14 cohorts with blood IL-6 measurements and follow-up data on any of 9 prespecified outcomes: myocardial infarction, stroke, atrial fibrillation, heart failure, total coronary heart disease (CHD), total CVD, all-cause mortality, CVD-specific mortality, and CHD-specific mortality. Multivariable-adjusted Cox proportional hazards models were used to estimate HRs and corresponding 95% CIs. IL-6 was analyzed by quartiles and as a log-transformed continuous variable. Associations were further examined by chronic kidney disease status, diabetes status, high-sensitivity C-reactive protein (hsCRP) concentrations, body mass index categories, as well as in secondary prevention. Discrimination was evaluated using the area under the curve across 4 models: base, base plus IL-6, base plus hsCRP, and base plus both markers.

resultsAmong 59,396 participants, the median IL-6 concentration was 1.91 pg/mL. The mean age was 63.6 ± 12.4 years. 67.6% were women, and 20.6% were Black. The longest median follow-up time was 15.8 years (for CVD-specific mortality). Higher IL-6 concentrations were associated with increased risk for all 9 outcomes. The strongest association was observed for CHD-specific mortality, with an adjusted HR of 2.12 (95% CI: 1.88-2.39) in the highest compared with the lowest IL-6 quartile. The weakest association was for myocardial infarction (HR: 1.45; 95% CI: 1.28-1.64). Findings were robust and consistent in all key subgroups as well as in secondary prevention. IL-6 alone demonstrated modest additive discrimination beyond hsCRP for stroke, heart failure, CVD, CHD, and mortality.

conclusionsIn this large, harmonized, individual-level participant data analysis of prospective cohorts, higher IL-6 concentrations were strongly associated with 9 cardiovascular and mortality outcomes after controlling for clinical covariates. These associations were consistent across cardiometabolic subgroups, chronic kidney disease status, and secondary prevention populations, highlighting the broad and consistent role of IL-6-mediated inflammation in cardiovascular risk.

Indexed as

Cardiovascular DiseasesInterleukin-6AgedBiomarkersCohort StudiesC-Reactive ProteinFemaleFollow-Up StudiesHumansMaleMiddle AgedPrognosisProspective StudiesBiomarkersC-Reactive ProteinInterleukin-6biomarkersCVDIL-6systemic inflammation

Identifiers

PMID42201287
PMCPMC13616589

What Socratic holds

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Registered trials

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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.