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Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0003-2247-8454
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2017 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 5, p. 379-384Article in journal (Refereed) Published
Abstract [en]

Background Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice. Objective To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk. Methods In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median followup 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n= 725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate > 70% in both cohorts. Results Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-proBNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p< 0.0001). Conclusions Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP , 2017. Vol. 103, no 5, p. 379-384
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Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:uu:diva-320847DOI: 10.1136/heartjnl-2016-309764ISI: 000395671900012PubMedID: 27609943OAI: oai:DiVA.org:uu-320847DiVA, id: diva2:1091363
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-04-26Bibliographically approved

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Lind, LarsSundström, JohanStenemo, MarkusHagström, EmilÄrnlöv, Johan

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