{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:45:37Z","timestamp":1791384337034,"version":"4.3.3"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Growth 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>We followed 3374 stroke- and dementia-free individuals (mean age, 59.0\u00b19.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8\u00b13.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing \u22484.0\u00b11.7 years after the sixth examination.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              After 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 (\n              <jats:italic>\u03b2<\/jats:italic>\n              coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: \u22120.71% for GDF-15;\n              <jats:italic>P<\/jats:italic>\n              =0.002 and 0.47% for sST2;\n              <jats:italic>P<\/jats:italic>\n              =0.02) and worse performance on the visual reproduction test (\n              <jats:italic>\u03b2<\/jats:italic>\n              coefficients for Q4 versus Q1: \u22120.62 for GDF-15;\n              <jats:italic>P<\/jats:italic>\n              =0.009 and \u22120.40 for sST2;\n              <jats:italic>P<\/jats:italic>\n              =0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (\n              <jats:italic>\u03b2<\/jats:italic>\n              for Q4 versus Q1=0.19;\n              <jats:italic>P<\/jats:italic>\n              =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\n              <jats:italic>P<\/jats:italic>\n              =0.03.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Circulating 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.115.009026","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T02:50:44Z","timestamp":1438138244000},"page":"2568-2575","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke"],"prefix":"10.1161","volume":"46","author":[{"given":"Charlotte","family":"Andersson","sequence":"first","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Preis","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Beiser","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"DeCarli","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai C.","family":"Wollert","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Wang","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"James L.","family":"Januzzi","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"From 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 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