Author + information
- Received March 6, 2019
- Revision received August 12, 2019
- Accepted August 14, 2019
- Published online October 30, 2019.
- Michael G. Silverman, MD, MPHa,
- Ashish Yeri, PhDa,
- M. Vinayaga Moorthy, PhDb,
- Fernando Camacho Garcia, BSa,
- Neal A. Chatterjee, MD, MSca,c,
- Charlotte S.A. Glinge, MDd,
- Jacob Tfelt, MD, DMScd,e,
- Ane M. Salvador, PhDa,
- Alexander R. Pico, PhDf,
- Ravi Shah, MD, MSca,
- Christine M. Albert, MD, MPHb,∗ and
- Saumya Das, MD, PhDa,∗∗ ()
- aCardiology Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bCenter for Arrhythmia Prevention, Divisions of Preventive and Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- cCardiology Division, University of Washington, Medical Center, Seattle, Washington
- dDepartment of Cardiology, Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- eDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- fInstitute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, California
- ↵∗Address for correspondence:
Dr. Saumya Das, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Simches Research Center, Third Floor, 185 Cambridge Street, Charles River Plaza, Boston, Massachusetts 02114.
Objectives This study evaluated whether plasma miRNAs were specifically associated with sudden cardiac and/or arrhythmic death (SCD) in a cohort of patients with coronary heart disease (CHD), most of whom were without primary prevention implantable cardioverter-defibrillators.
Background Novel biomarkers for sudden death risk stratification are needed in patients with CHD to more precisely target preventive therapies, such as implantable cardioverter-defibrillators. miRNAs have been implicated in regulating inflammation and cardiac fibrosis in cells, and plasma miRNAs have been shown to predict cardiovascular death in patients with CHD.
Methods We performed a nested case control study within a multicenter cohort of 5,956 patients with CHD followed prospectively for SCD. Plasma levels of 18 candidate miRNAs previously associated with cardiac remodeling were measured in 129 SCD cases and 258 control subjects matched on age, sex, race, and left ventricular ejection fraction.
Results miR-150-5p, miR-29a-3p, and miR-30a-5p were associated with increased SCD risk (odds ratios and 95% confidence intervals: 2.03 [1.12 to 3.67]; p = 0.02; 1.93 [1.07 to 3.50]; p = 0.02; 0.55 [0.31 to 0.97]; p = 0.04, respectively, for third vs. first tertile miRNA level). Unfavorable levels of all 3 miRNAs was associated with a 4.8-fold increased SCD risk (1.59 to 14.51; p = 0.006). A bioinformatics-based approach predicted miR-150-5p, miR-29a-3p, and miR-30a-5p to be involved in apoptosis, fibrosis, and inflammation.
Conclusions These findings suggest that plasma miRNAs may regulate pathways important for remodeling and may be useful in identifying patients with CHD at increased risk of SCD.
↵∗ Drs. Albert and Das contributed equally to this work and are joint senior authors.
This work was supported by research grants from the National Heart, Lung, and Blood Institute (R01HL091069, R01HL122547); the National Institutes of Health Common Fund exRNA Communication Program (UH3-TR000901); and St Jude Medical Inc. and St Jude Medical Foundation. Dr. Silverman was supported by the John S. Ladue Memorial Fellowship from Harvard Medical School. Dr. Shah is a consultant for MyoKardia, Inc., Amgen, Inc., Best Doctors, Inc., and KOLGroups, Inc., none of which participated in this study. Dr. Albert is a consultant for MyoKardia and Sanofi; and received grants from St Jude Medical, National Institutes of Health, Abbott, and Roche Diagnostics outside the submitted work. Dr. Das is a founding member of Dyrnamix, which had no role in this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received March 6, 2019.
- Revision received August 12, 2019.
- Accepted August 14, 2019.
- 2019 American College of Cardiology Foundation
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