Evidence map›Paper›PMID 39993026›Full record

ArticleStroke2025

Impact of Conventional Stroke Risk Factors on Early- and Late-Onset Ischemic Stroke: A Mendelian Randomization Study.

Kevin T K Nguyen, Huichun Xu, Brady J Gaynor, Patrick F McArdle, Timothy D O'Connor, James A Perry, Bradford B Worrall, Rainer Malik, Giorgio B Boncoraglio, Sally N Adebamowo and 5 more

Abstract read
In one paragraph

Article in Stroke, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. ESO annual stroke evidence update 2025.European stroke journal · 2026
    Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Kevin T K NguyenDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.ORCID 0009-0005-3635-6628
Huichun XuDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0001-8118-9607
Brady J GaynorDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0002-4142-0613
Patrick F McArdleDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.
Timothy D O'ConnorDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.
James A PerryDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0001-5050-2074
Bradford B WorrallDepartment of Neurology and Department of Public Health Sciences, University of Virginia, Charlottesville (B.B.W.).ORCID 0000-0001-9386-4091
Rainer MalikInstitute for Stroke and Dementia Research, Ludwig-Maximilians-University of Munich, Germany (R.M.).ORCID 0000-0001-9212-2520
Giorgio B BoncoraglioDepartment of Neurology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy (G.B.B).ORCID 0000-0002-2551-525X
Sally N AdebamowoDepartment of Epidemiology and Public Health (S.N.A.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0003-4713-2433
Ramin ZandDepartment of Neurology, College of Medicine, The Pennsylvania State University, Hershey (R.Z.).ORCID 0000-0002-9477-0094
John W ColeDepartment of Epidemiology and Public Health (S.N.A.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0001-9263-8930
Steven J KittnerDepartment of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0002-8457-8744
Braxton D MitchellDepartment of Medicine (K.T.K.N., H.X., B.J.G., P.F.M, T.D.O., J.A.P., B.D.M.), University of Maryland School of Medicine, Baltimore.ORCID 0000-0003-4920-4744
Stroke Genetic Network and Early-Onset Stroke Consortia

Funding

University of Maryland Claude D. Pepper Older Americans Independence Center (UM-OAIC)P30AG028747 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI ALICE S. RYAN · 2006 to 2026
$28.9M
RESEARCH TRAINING IN THE EPIDEMIOLOGY OF AGINGT32AG000262 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI ANN L GRUBER-BALDINI, DENISE L ORWIG · 1998 to 2026
$8.2M
Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry - Study SitesU01HG011717 · NHGRI · UNIVERSITY OF MARYLAND BALTIMORE · PI ADEBAMOWO, SALLY NNEOMA, TAYO, BAMIDELE OLUSEGUN · 2021 to 2025
$4.6M
Genetics of ischemic stroke in the SiGN ConsortiumR01NS100178 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2017 to 2021
$3.0M
Genetics of Early-Onset Ischemic Stroke ConsortiumR01NS105150 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2018 to 2022
$3.0M
CNV And Stroke (CaNVAS)R01NS114045 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI COLE, JOHN W. · 2020 to 2024
$2.6M
NHGRI NIH HHS U01 HG011717NIA NIH HHS P30 AG028747NIA NIH HHS T32 AG000262NINDS NIH HHS R01 NS100178NINDS NIH HHS R01 NS105150NINDS NIH HHS R01 NS114045
6 · The paper itself

Abstract

backgroundStroke incidence is decreasing in older ages but increasing in young adults. These divergent trends are at least partially attributable not only to diverging trends in stroke risk factors but may also be due to differences in the impact of stroke risk factors at different ages. To address this latter possibility, we used Mendelian randomization to assess differences in the association of stroke risk factors between early-onset ischemic stroke ([EOS]; onset 18-59 years) and late-onset ischemic stroke ([LOS]; onset ≥60 years).

methodsWe identified genetic variants from the GWAS Catalog for use as instrumental variables to proxy conventional stroke risk factors and then estimated the effects of these variants on risk factors in younger and older individuals in the UK Biobank. We then used these estimates to estimate the causal effects of stroke risk factors on EOS (n=6728 cases) and LOS (n=9272) cases from SiGN (Stroke Genetic Network) and the EOSC (Early-Onset Stroke Consortium). Lastly, we compared odds ratios between EOS and LOS, stratified by TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtypes, to determine if differences between estimates could be attributed to differences in stroke subtype distributions.

resultsEOS was associated with higher levels of body mass index, blood pressure, type 2 diabetes, and lower levels of HDL (high-density lipoprotein) cholesterol (all

conclusionsThese results support a causal relationship between body mass index, blood pressure, type 2 diabetes, and HDL cholesterol levels with EOS and blood pressure levels in LOS. Interventions that target these traits may reduce stroke risk.

Indexed as

Ischemic StrokeMendelian Randomization AnalysisStrokeAdolescentAdultAgedAge of OnsetDiabetes Mellitus, Type 2FemaleGenome-Wide Association StudyHumansMaleMiddle AgedRisk FactorsYoung Adultischemic strokeMendelian randomization analysisrisk factorsstrokeyoung adult

Identifiers

PMID39993026
PMCPMC11856430

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.