Use of biomarkers to establish potential role and function of circulating microRNAs in acute heart failure

Eline L. Vegter, Daniela Schmitter, Yanick Hagemeijer, Ekaterina S. Ovchinnikova, Pim van der Harst, John R. Teerlink, Christopher M. O'Connor, Marco Metra, Beth A. Davison, Daniel Bloomfield, Gad Cotter, John G. Cleland, Michael M. Givertz, Piotr Ponikowski, Dirk J. van Veldhuisen, Peter van der Meer, Eugene Berezikov, Adriaan A. Voors*, Mohsin A. F. Khan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers.

Methods: Associations between 16 biomarkers predictive for 180 day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48 hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis.

Results: No significant correlations were found at hospital admission. However, after 48 hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n = 21); miR-16-5p was correlated to C-reactive protein (R = -0.66, p-value = 0.0027), miR-106a-5p to creatinine (R = -0.68, p-value = 0.002), miR-223-3p to growth differentiation factor 15 (R = -0.69, p-value = 0.0015), miR-652-3p to soluble ST-2 (R = -0.77, p-value <0.001), miR-199a-3p to procalcitonin (R = -0.72, p-value <0.001) and galectin-3 (R = -0.73, p-value <0.001) and miR-18a-5p to procalcitonin (R = -0.68, p-value = 0.002). MiRNA target prediction and pathway analysis identified several pathways related to cardiac diseases, which could be linked to some of the miRNA-biomarker correlations.

Conclusions: The majority of correlations between circulating AHF-specific miRNAs were related to biomarkers predictive for a worse clinical outcome in a subgroup of worsening heart failure patients at 48 hours of hospitalization. The selective findings suggest a time-dependent effect of circulating miRNAs and highlight the susceptibility to individual patient characteristics influencing potential relations between miRNAs and biomarkers. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalInternational Journal of Cardiology
Publication statusPublished - 1-Dec-2016


  • Acute heart failure
  • Circulating microRNAs
  • Biomarkers
  • Correlation analysis
  • Pathways

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