医学
内科学
冲程(发动机)
嗜酸性阳离子蛋白
利钠肽
蛋白质组学
免疫学
生物信息学
肿瘤科
嗜酸性粒细胞
心力衰竭
生物
机械工程
基因
生物化学
工程类
哮喘
作者
Lars Lind,Agneta Siegbahn,Bertil Lindahl,Markus Stenemo,Johan Sundström,Johan Ärnlöv
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2015-12-01
卷期号:46 (12): 3340-3347
被引量:73
标识
DOI:10.1161/strokeaha.115.010829
摘要
Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers.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.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).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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