Omega-3 PUFAs and Reduced Risk for Heart Failure

Study Questions:

Is the plasma eicosapentaenoic acid (EPA) abundance (%EPA) associated with reduced hazard for primary heart failure (HF) events? Specifically, the authors tested the following hypotheses: 1) Is plasma %EPA inversely associated with all HF incidences, 2) is high plasma %EPA inversely associated with incidence of HF with preserved ejection fraction (HFpEF), and 3) is the inverse association of high plasma %EPA with HF incidence unique among omega-3 polyunsaturated fatty acids (PUFAs)?


In the MESA (Multi-Ethnic Study of Atherosclerosis) cohort, the study authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced EF (HFrEF) (EF <45%) and HFpEF (EF ≥45%) using Cox proportional hazards modeling. They tested for associations of EPA with HF risk using a four-step approach: 1) testing a univariate association; 2) adjusting for age, gender, race, and study center; 3) adjusting for other lead fatty acids; and 4) adjusting for other known risk factors.


A total of 6,562 participants (of the 6,814 total MESA participants) 45-84 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 HFrEF, 110 HFpEF, and 54 with unknown EF status. Median %EPA was 0.70% for all MESA participants. %EPA in HF-free participants was 0.76% (0.75-0.77%), but was lower in participants with HF at 0.69% (0.64-0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.91 per log-unit difference in %EPA; p = 0.004). Adjusting for age, gender, 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. The final adjusted HR for docosahexaenoic acid (DHA) abundance (%DHA) was 0.51 (95% CI, 0.38-0.70; p < 0.0001); for proportion omega-3 DPA, it was 0.59 (95% CI, 0.37-0.95; p = 0.03); and for %EPA plus %DHA, it was 0.54 (95% CI, 0.39-0.73). Sensitivity analyses showed no dependence on HF type.


The study authors concluded that higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF.


The important findings of this study raise questions such as, 1) “Is the reduced risk of HF mainly in ischemic cardiomyopathy patients?” 2) “What is the mechanism for the reduced risk of HF?” because it is well known that low-density lipoprotein cholesterol levels increase in patients treated with the triglyceride-lowering omega-3 fatty acids, and as authors point out, 3) “Is there a threshold level for the protective effect of EPA?” Prospective, randomized studies are needed to confirm the important findings of this study.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Acute Heart Failure

Keywords: Cardiomyopathies, Cholesterol, LDL, Docosahexaenoic Acids, Dyslipidemias, Eicosapentaenoic Acid, Fatty Acids, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Geriatrics, Heart Failure, Metabolic Syndrome, Primary Prevention, Risk Factors, Stroke Volume, Triglycerides

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