OC 45.1 - Circulatory microRNA-411-5p as a novel prognostic biomarker for major adverse cardiac events in patients with atrial fibrillation

Monday, July 11, 2022

2:45 PM – 3:00 PM

Location: ExCel Center, ICC Capital Suite Room 8&9

Presentation Format: In-Person

Presenting Author(s)

Stephan Nopp, MD

PhD Student
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria

Co-Author(s)

Mv

M L. van der Bent

Postdoc
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Oliver Königsbrügge, MD PhD

Physician Scientist
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Daniel Kraemmer, MD

PhD Student
Department of Medicine I, Clinical Division of Haematology and Haemostaseology; Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Johann Wojta, PhD

Professor
Medical University of Vienna
Vienna, Wien, Austria
Ingrid Pabinger, MD

Co-Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
Cihan Ay, MD

Professor, Head of the Thrombosis and Haemostasis Research Group
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Vienna, Wien, Austria
AN

Anne Y. Nossent

Professor
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Background: Reliable risk prediction of cardiovascular (CV) events in patients with atrial fibrillation (AF) is essential for optimizing prevention strategies. However, current clinical and routine laboratory markers lack accuracy in predicting major adverse cardiovascular events (MACE).

Aims: In this study, we sought to investigate circulating microRNAs as prognostic biomarkers for MACE in patients with AF.

Methods: We conducted a 3-stage nested case-control study on 418 patients with AF, who were followed-up for the occurrence of MACE (stroke, myocardial infarction, or CV death). First, total small-RNA sequencing was performed in 13 patients with MACE and 13 controls matched by age, sex, and CHA2DS2-VASc score. Eight candidate microRNAs showing differential expression in CV death were selected and measured using reverse-transcription quantitative polymerase chain reaction (qPCR) in 42 patients with CV death and 55 matched controls. To validate our findings and investigate broader clinical applicability, we also measured these microRNAs in 37 patients with MACE and 65 controls. Results of the qPCR-measurements for each candidate microRNA were handled according to a data-handling pipeline and analyzed using Cox regression.

Results: In the screening cohort, we detected 184 well-expressed microRNAs but did not find differentially expressed microRNAs below an FDR-adjusted p-value threshold of 0.05 for predicting MACE. However, significant results were obtained in the subgroup of patients with CV death. We, therefore, proceeded with a nested case-control study on patients with CV death and selected 8 microRNAs (miR-483-3p, miR-122-3p, miR-150-5p, miR-127-3p, miR-1908-5p, miR-15a-5p, miR-411-5p, and miR-625-5p) for further qPCR-analysis. In those, microRNA-411-5p was associated with CV death with a hazard ratio (HR) of 1.98 (95%CI 1.06-3.72). Validation in patients who developed MACE held similar findings; microRNA-411-5p showed an HR of 2.12 (95%CI 1.16-4.11) for the occurrence of MACE.

Conclusion(s): Circulating microRNA-411-5p could be a valuable prognostic biomarker for MACE in patients with AF.