Evidence map›Paper›PMID 26219649›Full record

ArticleStroke2015

Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke.

Charlotte Andersson, Sarah R Preis, Alexa Beiser, Charles DeCarli, Kai C Wollert, Thomas J Wang, James L Januzzi, Ramachandran S Vasan, Sudha Seshadri

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 3 pooled it
4.0field-weighted citation impact, top 6% of its field
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

44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 citations in OpenAlex.

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  10. Heart-Brain Axis: Subclinical Cardiovascular Changes and Brain Health.Journal of the American Heart Association · 2026
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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

9 authors at 5 institutions in 3 countries.

Charlotte AnderssonFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.). ca@heart.dk.
Sarah R PreisFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Alexa BeiserFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Charles DeCarliFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Kai C WollertFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Thomas J WangFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
James L JanuzziFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Ramachandran S VasanFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Sudha SeshadriFrom the Framingham Heart Study, MA (C.A., A.B., T.J.W., R.S.V., S.S.); Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark (C.A.); Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., A.B.); Department of Neurology (A.B., S.S.) and Section of Preventive Medicine and Cardiology (R.S.V.), Boston University School of Medicine, MA; Department of Neurology, University of California at Davis, Sacramento (C.D.); Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany (K.C.W.); Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN (T.J.W.); and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.).
Medizinische Hochschule Hannover · DEUniversity of California, Davis · USVanderbilt University · USBoston University · USUniversity of Copenhagen · DK

Funding

UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI RAJAN, KUMAR B. · 1991 to 2020
$28.3M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
MRI, Genetics &Cognitive Precursors of AD &DementiaR01AG016495 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA · 1999 to 2016
$12.5M
MRI, Cognitive, Genetic & Biomarker Precursors of AD & Dementia in Young AdultsR01AG033040 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 2009 to 2019
$11.2M
Preclinical AD: Correlates of Amyloid, Tau PET and fcMRI in Framingham Gen 3 Young AdultsR01AG049607 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2015 to 2019
$3.1M
Neurotrophic Factors: Genetic Variation and Serum Levels in Brain AgingR01AG031287 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2010
$1.2M
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS N01 HC025195NIA NIH HHS AG016495NIA NIH HHS AG081220NIA NIH HHS NIA AG10129NIA NIH HHS P30 AG010129NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG016495NIA NIH HHS R01 AG031287NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG049607NINDS NIH HHS NS17950NINDS NIH HHS R01 NS017950
6 · The paper itself

Abstract

background and purposeGrowth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort.

methodsWe followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination.

resultsAfter adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (β coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (β coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03.

conclusionsCirculating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury.

Indexed as

AgedBiomarkersBrainCerebrovascular TraumaCognition DisordersCross-Sectional StudiesFemaleGrowth Differentiation Factor 15HumansInterleukin-1 Receptor-Like 1 ProteinIschemic Attack, TransientLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedReceptors, Cell SurfaceBiomarkersGrowth Differentiation Factor 15IL1RL1 protein, humanInterleukin-1 Receptor-Like 1 ProteinReceptors, Cell Surfacefollow-up studiesgrowth differentiation factor-15magnetic resonance imagingneuroimagingstroke

Identifiers

PMID26219649
PMCPMC4550531
OpenAlexW2167964400

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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.