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 α, 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.
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 α, growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumornecrosis 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.
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Authors: Antonela Bicvic; Natalie Scherrer; Juliane Schweizer; Felix Fluri; Mirjam Christ-Crain; Gian Marco De Marchis; Andreas R Luft; Mira Katan Journal: Eur Stroke J Date: 2022-04-20
Authors: Lars Lind; Bruna Gigante; Yan Borné; Tobias Feldreich; Jerzy Leppert; Pär Hedberg; Carl Johan Östgren; Fredrik H Nyström; Johan Sundström; Johan Ärnlöv; Damiano Baldassarre; Elena Tremoli; Fabrizio Veglia; Anders Hamsten; Christopher J O'Donnell; Nora Franceschini; Marju Orho-Melander; Jan Nilsson; Olle Melander; Gunnar Engström; Anders Mälarstig Journal: Arterioscler Thromb Vasc Biol Date: 2021-03-04 Impact factor: 8.311
Authors: Alexandru Schiopu; Eva Bengtsson; Isabel Gonçalves; Jan Nilsson; Gunilla Nordin Fredrikson; Harry Björkbacka Journal: J Am Heart Assoc Date: 2016-09-13 Impact factor: 5.501