Improved risk stratification in prevention by use of a panel of selected circulating microRNAs

  • Risk stratification is crucial in prevention. Circulating microRNAs have been proposed as biomarkers in cardiovascular disease. Here a miR panel consisting of miRs related to different cardiovascular pathophysiologies, was evaluated to predict outcome in the context of prevention. MiR-34a, miR-223, miR-378, miR-499 and miR-133 were determined from peripheral blood by qPCR and combined to a risk panel. As derivation cohort, 178 individuals of the DETECT study, and as validation cohort, 129 individuals of the SHIP study were used in a case-control approach. Overall mortality and cardiovascular events were outcome measures. The Framingham Risk Score(FRS) and the SCORE system were applied as risk classification systems. The identified miR panel was significantly associated with mortality given by a hazard ratio(HR) of 3.0 (95% (CI): 1.09–8.43; p = 0.034) and of 2.9 (95% CI: 1.32–6.33; p = 0.008) after adjusting for the FRS in the derivation cohort. In a validation cohort the miR-panel had a HR of 1.31 (95% CI: 1.03–1.66; p = 0.03) and of 1.29 (95% CI: 1.02–1.64; p = 0.03) in a FRS/SCORE adjusted-model. A FRS/SCORE risk model was significantly improved to predict mortality by the miR panel with continuous net reclassification index of 0.42/0.49 (p = 0.014/0.005). The present miR panel of 5 circulating miRs is able to improve risk stratification in prevention with respect to mortality beyond the FRS or SCORE.

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Author:Till KellerORCiDGND, Jes-Niels Boeckel, Stefan Groß, Jens KlotscheORCiDGND, Lars Palapies, David LeistnerORCiDGND, Lars Pieper, Günnter K. Stalla, Hendrik Lehnert, Sigmund Silber, David Pittrow, Winfried MärzORCiDGND, Marcus DörrORCiDGND, Hans-Ulrich Wittchen, Sebastian E. Baumeister, Uwe Völker, Stephan B. Felix, Stefanie DimmelerORCiDGND, Andreas M. ZeiherORCiDGND
URN:urn:nbn:de:hebis:30:3-486075
DOI:https://doi.org/10.1038/s41598-017-04040-w
ISSN:2045-2322
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28674420
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/07/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/01/17
Tag:Prognostic markers; miRNAs
Volume:7
Issue:1, Art. 4511
Page Number:9
First Page:1
Last Page:9
Note:
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS-PPN:446224286
Institutes:Medizin / Medizin
Exzellenzcluster / Exzellenzcluster Herz-Lungen-System
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0