Omega-3 Appears to Lower Heart-Disease Risk, More So in Hyperlipidemia

Marlene Busko

January 09, 2017

ANN ARBOR, MI — A study[1] consisting of a meta-analysis of randomized controlled trials (RCTs) and another meta-analysis of prospective observational cohort studies suggests that the American Heart Association (AHA) recommendation of at least 1 g/day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is reasonable to lower risk of coronary heart disease (CHD) events.

The findings also suggest that patients with high levels of triglycerides or LDL cholesterol would benefit most by optimal intake of these omega-3 fatty acids.

In the meta-analysis of RCTs, intake of omega-3 fatty acids (EPA/DHA) from food or supplements vs controls was associated with a nonsignificant 6% lower rate of CHD—defined as MI, sudden cardiac death, coronary death, or angina.

Delving deeper, intake of omega-3 fatty acid was associated with a significantly lower risk of CHD only in patients with high initial levels of triglycerides (>150 mg/dL) or LDL cholesterol (>130 mg/dL).

In the meta-analysis of prospective cohort studies, a high vs low intake of omega-3 fatty acid was associated with a significant 18% lower rate of CHD.

"Authoritative bodies recommend intake of EPA and DHA for heart and overall health, [and] our comprehensive meta-analysis of data from RCTs and prospective cohort studies supports this recommendation," Dr Dominik D Alexander (EpidStat Institute, Ann Arbor, MI) and colleagues conclude, in their study published in the January 2017 issue of Mayo Clinic Proceedings.

This study was comprehensive and unique in that it specifically focused on how EPA and DHA affect CHD, whereas other meta-analyses have looked at a broader scope of outcomes, according to the researchers. "To our knowledge, this is the most comprehensive quantitative assessment of the relationship between EPA/DHA supplementation and intake and CHD risk to date. Our inclusion criteria were specific for CHD, which distinguishes our findings from those of other meta-analyses that included a mixture of vascular as well as less well defined coronary outcomes."

The findings are important since about one in four adults in the US has elevated triglyceride levels and a similar number have elevated LDL-cholesterol levels, they note.

"Several large RCTs are currently under way that should help to clarify the issues surrounding the dosing and indications for omega-3 fatty acids," which were not addressed in the current study, Drs James H O'Keefe and Dany Jacob (University of Missouri-Kansas City, Kansas City, MO) and Dr Carl J Lavie (John Ochsner Heart and Vascular Institute, New Orleans, LA) write in an accompanying editorial[2].

"In the meantime, omega-3 fatty-acid intake of at least 1 g of EPA and DHA per day, either from seafood or supplementation (as recommended by the American Heart Association) continues to be a reasonable strategy."

"It's very reasonable, based on evidence for benefits and absence of harm, to recommend omega-3 intake for potential cardiovascular protection," Dr Dariush Mozaffarian (Tufts University, Boston, MA), who was not involved with the study, agreed in an email to heartwire from Medscape. "And it's very likely that some intake is better than none; [however], the optimal target level as well as potential variation by patient population remain uncertain."

Two Types of Meta-Analysis

Studies examining the effect of omega-3 intake on CHD events have reported mixed results, Alexander and colleagues write.

They searched the literature from 1947 to November 2, 2015 and identified 18 RCTs (with approximately 93,000 patients) and 16 prospective cohort studies (with approximately 732,000 patients) that looked at the effect of EPA and DHA intake on CHD events.

EPA and DHA reduced the risk of CHD events by 6% to 18% in the two meta-analyses.

Reduction in CHD Risk With EPA + DHA Intake vs Control in 18 RCTs

  Summary relative risk estimate (95% CI)
Overall 0.94 (0.85–1.05)
Initial high triglycerides 0.84 (0.76–0.98)
Initial high LDL cholesterol 0.86 (0.76–0.98)

Reduction in CHD Risk With High vs Low EPA + DHA Intake in 16 Prospective Cohort Studies

  Summary relative risk estimate (95% CI)
Overall 0.82 (0.74–0.92)

The beneficial findings in patients with elevated lipids is "particularly relevant," since about 25% of Americans age 20 and older have elevated triglyceride levels, and about 27% of 40- to 74-year-old Americans have elevated LDL cholesterol, Alexander and colleagues note.

However, these meta-analyses are subject to inherent limitations (such as inconsistent measures in the component trials), and the study did not investigate optimal dose.

Further RCTs with more homogeneous omega-3 intake and CHD outcomes and longer follow-up will provide "a better understanding of the promising beneficial relationship between EPA/DHA and CHD risk," they write.

"For the general population, modest consumption (about 250 mg/day EPA+DHA) may be sufficient," Mozaffarian suggested. "For higher-risk patients, such as those with prior MI and/or high triglycerides, a higher target is not unreasonable," and results of ongoing trials "will be very useful to better understand potential benefits in this particular patient population," he said.

The study was supported by a grant from the Global Organization for EPA and DHA Omega-3s (GOED), Salt Lake City, UT. Alexander was employed by the Center for Epidemiology, Biostatistics, and Computational Biology of Exponent, Chicago, IL, at the time of his primary contribution to this research, and Exponent received funding to conduct this research through the GOED. Disclosures for the coauthors are listed in the paper. O'Keefe is chief medical officer and founder of CardioTabs, a nutraceutical company, and has a major ownership interest in the company, which sells products that contain omega-3. Lavie is a speaker for Amarin on its icosapent-ethyl product Vascepa, has consulted for DSM Nutritional Products, and made an omega-3 educational video at the American Heart Association meeting on November 14, 2016, for GOED. Mozaffarian has no relevant financial relationships. Mozaffarian reports reports ad hoc honoraria or consulting fees from Boston Heart Diagnostics, Haas Avocado Board, AstraZeneca, GOED, DSM, and Life Sciences Research Organization and chapter royalties from UpToDate.

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