Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation
The risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. W...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3861 |
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| author | Stephan Nopp M. Leontien van der Bent Daniel Kraemmer Oliver Königsbrügge Johann Wojta Ingrid Pabinger Cihan Ay Anne Yaël Nossent |
| author_facet | Stephan Nopp M. Leontien van der Bent Daniel Kraemmer Oliver Königsbrügge Johann Wojta Ingrid Pabinger Cihan Ay Anne Yaël Nossent |
| author_sort | Stephan Nopp |
| collection | DOAJ |
| description | The risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. We conducted a three-stage nested case–control study within the framework of a prospective registry, including 347 AF patients. First, total small RNA-sequencing was performed in 26 patients (13 cases with MACE) and the differential expression of microRNAs was analyzed. Seven candidate microRNAs with promising results in a subgroup analysis on cardiovascular death were selected and measured via using RT-qPCR in 97 patients (42 cases with cardiovascular death). To further validate our findings and investigate broader clinical applicability, we analyzed the same microRNAs in a subsequent nested case–control study of 102 patients (37 cases with early MACE) by using Cox regression. In the microRNA discovery cohort (n = 26), we detected 184 well-expressed microRNAs in circulation without overt differential expression between the cases and controls. A subgroup analysis on cardiovascular death revealed 26 microRNAs that were differentially expressed at a significance level < 0.05 (three of which with an FDR-adjusted <i>p</i>-value <0.05). We, therefore, proceeded with a nested case–control approach (n = 97) focusing on patients with cardiovascular death and selected, in total, seven microRNAs for further RT-qPCR analysis. One microRNA, miR-411-5p, was significantly associated with cardiovascular death (adjusted HR (95% CI): 1.95 (1.04–3.67)). Further validation (n = 102) in patients who developed early MACE showed similar results (adjusted HR (95% CI) 2.35 (1.17–4.73)). In conclusion, circulating miR-411-5p could be a valuable prognostic biomarker for MACE in AF patients. |
| first_indexed | 2024-03-11T08:41:57Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:41:57Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-76233d9cbbc246c4b11bf9b0c92134132023-11-16T21:06:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244386110.3390/ijms24043861Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial FibrillationStephan Nopp0M. Leontien van der Bent1Daniel Kraemmer2Oliver Königsbrügge3Johann Wojta4Ingrid Pabinger5Cihan Ay6Anne Yaël Nossent7Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 Leiden, The NetherlandsClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 Leiden, The NetherlandsThe risk stratification of patients with atrial fibrillation (AF) for subsequent cardiovascular events could help in guiding prevention strategies. In this study, we aimed at investigating circulating microRNAs as prognostic biomarkers for major adverse cardiovascular events (MACE) in AF patients. We conducted a three-stage nested case–control study within the framework of a prospective registry, including 347 AF patients. First, total small RNA-sequencing was performed in 26 patients (13 cases with MACE) and the differential expression of microRNAs was analyzed. Seven candidate microRNAs with promising results in a subgroup analysis on cardiovascular death were selected and measured via using RT-qPCR in 97 patients (42 cases with cardiovascular death). To further validate our findings and investigate broader clinical applicability, we analyzed the same microRNAs in a subsequent nested case–control study of 102 patients (37 cases with early MACE) by using Cox regression. In the microRNA discovery cohort (n = 26), we detected 184 well-expressed microRNAs in circulation without overt differential expression between the cases and controls. A subgroup analysis on cardiovascular death revealed 26 microRNAs that were differentially expressed at a significance level < 0.05 (three of which with an FDR-adjusted <i>p</i>-value <0.05). We, therefore, proceeded with a nested case–control approach (n = 97) focusing on patients with cardiovascular death and selected, in total, seven microRNAs for further RT-qPCR analysis. One microRNA, miR-411-5p, was significantly associated with cardiovascular death (adjusted HR (95% CI): 1.95 (1.04–3.67)). Further validation (n = 102) in patients who developed early MACE showed similar results (adjusted HR (95% CI) 2.35 (1.17–4.73)). In conclusion, circulating miR-411-5p could be a valuable prognostic biomarker for MACE in AF patients.https://www.mdpi.com/1422-0067/24/4/3861circulating microRNAatrial fibrillationbiomarkerssequence analysisRNAhumans |
| spellingShingle | Stephan Nopp M. Leontien van der Bent Daniel Kraemmer Oliver Königsbrügge Johann Wojta Ingrid Pabinger Cihan Ay Anne Yaël Nossent Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation International Journal of Molecular Sciences circulating microRNA atrial fibrillation biomarkers sequence analysis RNA humans |
| title | Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation |
| title_full | Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation |
| title_fullStr | Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation |
| title_full_unstemmed | Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation |
| title_short | Circulatory miR-411-5p as a Novel Prognostic Biomarker for Major Adverse Cardiovascular Events in Patients with Atrial Fibrillation |
| title_sort | circulatory mir 411 5p as a novel prognostic biomarker for major adverse cardiovascular events in patients with atrial fibrillation |
| topic | circulating microRNA atrial fibrillation biomarkers sequence analysis RNA humans |
| url | https://www.mdpi.com/1422-0067/24/4/3861 |
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