Eline L Vegter1, Daniela Schmitter2, Yanick Hagemeijer1, Ekaterina S Ovchinnikova3, Pim van der Harst1, John R Teerlink4, Christopher M O'Connor5, Marco Metra6, Beth A Davison7, Daniel Bloomfield8, Gad Cotter7, John G Cleland9, Michael M Givertz10, Piotr Ponikowski11, Dirk J van Veldhuisen1, Peter van der Meer1, Eugene Berezikov12, Adriaan A Voors13, Mohsin A F Khan1. 1. Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. 2. Momentum Research, Inc., Hagmattstrasse 17, CH-4123 Allschwil, Switzerland. 3. Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands; European Research Institute for the Biology of Ageing and University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. 4. University of California at San Francisco, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. 5. Inova Heart and Vascular Institute, Falls Church, VA, USA. 6. Cardiology, The Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Italy. 7. Momentum Research, Durham, NC, USA. 8. Merck Research Laboratories, Rahway, NY, USA. 9. National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK. 10. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 11. Medical University, Clinical Military Hospital, Wroclaw, Poland. 12. European Research Institute for the Biology of Ageing and University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. 13. Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. Electronic address: a.a.voors@umcg.nl.
Abstract
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 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. 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 48hours, 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 48hours 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.
RCT Entities:
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 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. 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 48hours, 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 failurepatients at 48hours 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.
Authors: Eline L Vegter; Ekaterina S Ovchinnikova; Dirk J van Veldhuisen; Tiny Jaarsma; Eugene Berezikov; Peter van der Meer; Adriaan A Voors Journal: Clin Res Cardiol Date: 2017-03-14 Impact factor: 5.460
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