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Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
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2015 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 12, 3340-3347 p.Article in journal (Refereed) Published
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Abstract [en]

Background and Purpose-Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. Methods-We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. Results-In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of individual data, interleukin-27 subunit , growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001). Conclusions-Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke.

Place, publisher, year, edition, pages
2015. Vol. 46, no 12, 3340-3347 p.
Keyword [en]
adrenomedullin, natriuretic peptide, brain, proteins, risk factors, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-270960DOI: 10.1161/STROKEAHA.115.010829ISI: 000365534400001PubMedID: 26542692OAI: oai:DiVA.org:uu-270960DiVA: diva2:890845
Funder
AstraZenecaEU, European Research Council, 634869Swedish Research Council, 2012-1727Swedish Research Council, 2012-2215Swedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation
Available from: 2016-01-05 Created: 2016-01-05 Last updated: 2017-12-01Bibliographically approved

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Lind, LarsSiegbahn, AgnetaLindahl, BertilStenemo, MarkusSundström, JohanÄrnlöv, Johan

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Lind, LarsSiegbahn, AgnetaLindahl, BertilStenemo, MarkusSundström, JohanÄrnlöv, Johan
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Cardiovascular epidemiologyCoagulation and inflammation scienceCardiologyUCR-Uppsala Clinical Research CenterMolecular epidemiology
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Stroke
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