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A Multi-Cohort Meta...
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Lind, LarsKarolinska Institutet,Uppsala universitet,Klinisk epidemiologi
(author)
A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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Elsevier BV,2020
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LIBRIS-ID:oai:DiVA.org:uu-402618
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-402618URI
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https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104476DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:142691365URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:du-31198URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Background and Purpose:To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach.Methods: We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites.Results:In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR.69 per SD change, 95% CI.57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively).Conclusions:An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies.
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Salihovic, SamiraUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)samsa560
(author)
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Ganna, AndreaMassachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA
(author)
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Sundström, Johan,Professor,1971-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk epidemiologi(Swepub:uu)johasund
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Broeckling, Corey D.Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA
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Magnusson, Patrik K.Karolinska Institutet
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Pedersen, Nancy L.Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden
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Siegbahn, Agneta,1947-Uppsala universitet,Koagulation och inflammationsvetenskap(Swepub:uu)agsie424
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Prenni, JessicaColorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA
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Fall, Tove,1979-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)tovfa878
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Ingelsson, ErikStanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Cardiovasc Inst, Stanford, CA USA
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Ärnlöv, Johan,1970-Högskolan Dalarna,Karolinska Institutet,Medicinsk vetenskap(Swepub:du)jan
(author)
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Uppsala universitetKlinisk epidemiologi
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In:Journal of Stroke & Cerebrovascular Diseases: Elsevier BV29:21052-30571532-8511
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Uppsala University
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Karolinska Institutet
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Högskolan Dalarna