OT: fish oil vs heat disease

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New Updates on Fish Oil in Heart Failure Prevention
Clinical Context

Research regarding the effects of supplementation with omega-3 polyunsaturated fatty acids (PUFAs) on cardiovascular outcomes has been mixed, but the REDUCE-IT trial by Bhatt and colleagues was a breakthrough in terms of sound methodology and significant results. This study, published in the January 3, 2019, issue of the New England Journal of Medicine, included patients at high risk for cardiovascular events who were already treated with a statin and had hypertriglyceridemia. They were randomly assigned to receive either 2 g of icosapent ethyl (IE) twice daily or placebo. Icosapent ethyl is a precursor of eicosapentaenoic acid (EPA).

During a mean of nearly 5 years of follow-up, the IE treatment group experienced a significant 25% reduction in the risk for a composite of cardiovascular death and major cardiovascular events. Rates of stroke and myocardial infarction were significantly lower in the IE group, and the hazard ratio for cardiovascular death in comparing the IE and placebo groups was 0.80 (95% confidence interval [CI], 0.66-0.98). IE was associated with a higher risk for atrial fibrillation than placebo, and it was associated with a nonsignificant increase in the risk for serious bleeding events.

Research into the effects of omega-3 PUFAs on heart failure have also been mixed. The current study evaluates how plasma concentrations of omega-3 PUFAs might affect the risk for heart failure. ..........................

High plasma levels of the kinds of fatty acids found in fish oil were associated with a lower long-term risk for new heart failure (HF), whether with reduced or preserved ejection fraction (HFrEF or HFpEF), in a community-based cohort of more than 6000 people.

The higher the plasma levels of EPA (a prevalent n-3 PUFA also called omega-3 PUFA) were, the lower the risks for both forms of HF during a median follow-up of 13 years.

Similar independent observations were made for plasma levels of docosahexaenoic acid (DHA) and of EPA and DHA combined, suggesting that increased levels of n-3 PUFA in general may confer cardiovascular (CV) benefits, observe the study's authors, led by Robert C. Block, MD, MPH, from the University of Rochester School of Medicine and Dentistry, New York.

The findings from the Multi-Ethnic Study of Atherosclerosis (MESA), published July 10 in JACC: Heart Failure, supports existing data on the CV effects of elevated levels of n-3 PUFA, whether achieved by diet, supplements or prescription.

The MESA cohort consists of initially middle-aged adults and is noteworthy for being about evenly divided between women and men and including large proportions of African Americans and other nonwhite groups.

The analysis "may reopen the discussion on the role of omega-3 fatty acids in the context of prevention and treatment of HF," writes Aldo P. Maggioni, MD, from the Heart Care Foundation, Florence, Italy, in an accompanying editorial.

"This study clearly demonstrated a significant independent inverse correlation between circulating levels of omega-3 fatty acids, specifically [EPA], and the occurrence of HF over a long median follow-up period of 13 years." .....................................................................
As both the report and editorial note, n-3 PUFA supplementation at the fairly low dosage of 1 g/d, added to standard therapy, was associated with reduced all-cause mortality and HF hospitalization rates over the course of about 4 years in the 2008 GISSI-HF trial.

In the 2015 trial OMEGA-REMODEL, patients who took a proprietary n-PUFA preparation at 4 g/d for 6 months after an MI showed reductions in ventricular remodeling, fibrosis, and inflammatory markers.

More recently, in the REDUCE-IT trial, patients with raised triglycerides and CV disease or diabetes plus 1 other CV risk factor showed a 25% reduction in the composite outcome of CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina over the course of 5 years while receiving icosapent ethyl at 4 g/d. The agent acts as a precursor of EPA. ................................

In an analysis adjusted for age, sex, race, body mass index, smoking status, type 2 diabetes, blood pressure, lipids, lipid-lowering therapy, albuminuria, and types of PUFA, percent-EPA was inversely associated with risk for HF at a hazard ratio of 0.73 for each log-unit difference (P=.001). .................................

Study Highlights (HF= heart failure)

Researchers used MESA to assess their study question. This study enrolled 6814 adults between the ages of 45 and 84 years between 2000 and 2002.
All participants underwent a battery of tests at baseline, including measurement of plasma fatty acids.
The main outcome of the current study was HF.....................................................

Researchers divided participants with HF into preserved ejection fraction (ejection fraction of 45% or more; HFpEF) and reduced ejection fraction (ejection fraction, <45%; HFrEF) groups. ..........................

The main study analysis featured the relationship between plasma fatty acids and HF. The researchers performed multiple analyses to account for confounders in this relationship. ........................................

During a median follow-up period of 13 years, 292 participants were identified with HF, with a fairly equal representation of HFpEF and HFrEF. ............................

Concentrations of EPA and DHA in the plasma were inversely associated with the risk for HF in initial analyses. EPA and DHA concentrations were strongly correlated among individual participants. ...........................

For each log increase in the concentration of plasma EPA, the hazard ratio for HF was 0.73 (95% CI, 0.60-0.91).

The respective final adjusted hazard ratio for DHA concentration and risk for HF was 0.51 (95% CI, 0.38-0.70). Combining DHA and EPA concentrations, the hazard ratio for HF per log increase in plasma concentration was 0.54

REDUCE-IT demonstrated that the icosapent ethyl (IE) treatment group experienced a significant 25% reduction in the risk for a composite of CV death and major CV events compared with placebo. Rates of stroke and myocardial infarction were significantly lower in the IE group, and the hazard ratio for CV death in comparing the IE and placebo groups was 0.80 (95% CI, 0.66-0.98). IE was associated with a higher risk for atrial fibrillation than placebo, and it was associated with a nonsignificant increase in the risk for serious bleeding events. .....................................

The current study finds that plasma concentrations of both EPA and DHA are inversely associated with the risk for HF.

Implications for the Healthcare Team: There is growing evidence that both dietary and supplemental omega-3 PUFAs are associated with better CV outcomes. The healthcare team should encourage consumption of a diet which includes these fatty acids and suggest supplements for high-risk patients. ....................

Post Edited (BillyBob@388) : 9/20/2019 8:06:02 PM (GMT-6)