Author + information
- Received February 24, 2019
- Revision received March 19, 2019
- Accepted March 20, 2019
- Published online July 10, 2019.
- Robert C. Block, MDa,b,
- Linxi Liu, MSa,
- David M. Herrington, MDc,
- Shue Huang, MSd,
- Michael Y. Tsai, PhDe,
- Timothy D. O’Connell, PhDf,∗ ( and )
- Gregory C. Shearer, PhDd,∗ ()
- aDepartment of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, New York
- bCardiology Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York
- cCardiology, Epidemiology and Prevention, Wake Forest University, Winston-Salem, North Carolina
- dDepartment of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania
- eDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
- fDepartment of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota
- ↵∗Address for correspondence:
Dr. Gregory C. Shearer, Department of Nutritional Sciences, Pennsylvania State University, 110 Chandlee Laboratory, University Park, Pennsylvania 16802.
- ↵∗Dr. Timothy D. O’Connell, Department of Integrative Biology and Physiology, University of Minnesota, 6-125 Jackson Hall 321 Church Street S.E., Minneapolis, Minnesota 55455.
Objectives The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial.
Background Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear.
Methods In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling.
Results A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type.
Conclusions Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)
- docosahexaenoic acid
- eicosapentaenoic acid
- hazard ratio
- heart failure with preserved ejection fraction
- omega-3 fatty acids
This work was funded by grant 1 R01 HL130099-01A1 from the National Heart, Lung, and Blood Institute (Drs. O’Connell and Shearer). This research was also supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences. Drs. Herrington, O’Connell, and Shearer have received honoraria for training and advice from Amarin Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 24, 2019.
- Revision received March 19, 2019.
- Accepted March 20, 2019.
- 2019 American College of Cardiology Foundation
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