Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip
2015 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 12, 3340-3347 p.Article in journal (Refereed) PublishedText
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.
adrenomedullin, natriuretic peptide, brain, proteins, risk factors, stroke
Cardiac and Cardiovascular Systems
IdentifiersURN: urn:nbn:se:uu:diva-270960DOI: 10.1161/STROKEAHA.115.010829ISI: 000365534400001PubMedID: 26542692OAI: oai:DiVA.org:uu-270960DiVA: diva2:890845
FunderAstraZenecaEU, European Research Council, 634869Swedish Research Council, 2012-1727Swedish Research Council, 2012-2215Swedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation