More Circulating Omega-3s May Boost Prognosis After STEMI

Omega-3s may not keep a STEMI from happening in the first place, but higher levels of these fatty acids circulating in the blood may help protect against downstream events.

So suggests a study demonstrating that patients with higher serum levels of eicosapentaenoic acid (EPA)—reflecting intake of marine omega-3 fatty acids, mostly from fatty fish—at the time of their acute event had lower risks of MACE and cardiovascular readmissions over the next 3 years. Moreover, patients with higher circulating levels of alpha-linolenic acid (ALA)—a proxy for consumption of omega-3s from vegetables—had a lower risk of dying over that span.

“Now we have additional robust scientific evidence to strongly support that omega-3 fatty acids are integral components of heart-healthy dietary patterns,” senior author Antoni Bayés-Genís, MD, PhD (Heart Institute, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain), told TCTMD.

The study, with lead author Iolanda Lázaro, PhD (Instituto de Salud Carlos III, Madrid, Spain), was published online today ahead of the November 3, 2020, issue of the Journal of the American College of Cardiology.

Limiting Myocardial Damage

Diets that incorporate a lot of fatty fish intake, the main source of EPA, have been tied to lower cardiovascular risks. “Dietary EPA is readily incorporated into the phospholipids of cardiomyocyte membranes, where it partially displaces omega-6 arachidonic acid. Membrane accretion of EPA is believed to underlie most salutary cardiac effects associated with long-term consumption of fatty fish and fish oils,” the authors explain. “In addition to promoting more efficient myocardial oxygen consumption, membrane EPA protects against a variety of heart stressors.”

In the setting of an MI, cardiac ischemia induces cleavage of fatty acids from cardiomyocyte membranes. There is a pro-inflammatory process that enhances ischemic myocardial damage when omega-6 arachidonic acid is released, but an anti-inflammatory response when omega-3 EPA is released. “This observation gave rise to the notion that EPA enrichment in cardiac membranes, due to sustained consumption of fatty fish or fish oils, might limit the degree of myocardial damage in the event of an MI, which has been repeatedly confirmed in animal models,” with some evidence supporting that process in humans as well, the investigators write.

To assess whether greater intake of omega-3s is associated with a better prognosis after an acute MI, the researchers studied 944 consecutive patients with STEMI (mean age 61 years; 22% women) who underwent primary PCI at a tertiary university hospital. EPA and ALA levels at the time of STEMI were assessed by looking at the proportion of each omega-3 fatty acid in serum phosphatidylcholine, which gives an idea of dietary intake over the past 3 or 4 weeks.

During the 3-year follow-up, rates of MACE (all-cause mortality or readmission due to CV causes), all-cause mortality, and CV readmission were 22.4%, 11.4%, and 13.8%, respectively.

After adjustment for potential confounders, serum EPA levels were inversely associated with risks of MACE (HR 0.76 per 1-standard deviation [SD] increase in EPA; 95% CI 0.62-0.94) and CV readmission (HR 0.74 per 1-SD increase; 95% CI 0.58-0.95). The relationship with all-cause mortality was not significant (HR 0.91 per 1-SD increase; 95% CI 0.68-1.22).

Serum ALA levels were inversely related to all-cause mortality (HR 0.65 per 1-SD increase; 95% CI 0.44-0.96), with the association falling shy of significance for MACE (HR 0.81 per 1-SD increase; 95% CI 0.64-1.03).

Bayés-Genís acknowledged that the study is limited by its inability to account for potential differences in lifestyle behaviors between patients with higher or lower intake of omega-3s, noting that people who eat more ALA-rich nuts and seeds or EPA-rich oily fish tend to have better health habits in general.

Nevertheless, he said, “if I was a clinician reading this paper, my take-home message would be that I should recommend eating food rich in omega-3 fatty acids, both marine and vegetable fatty acids, in STEMI patients to reduce adverse events during follow-up.”

Supports Current Dietary Advice

Commenting for TCTMD, Alice Lichtenstein, DSc (Tufts University, Boston, MA), an author of the 2018 American Heart Association science advisory on seafood long-chain omega-3 polyunsaturated fatty acids and cardiovascular disease, said “this work solidifies and confirms a lot of other findings in the same area that higher levels of fish and very-long-chain unsaturated fatty acids, particularly the n-3 fatty acids, are associated with better cardiovascular outcomes.”

The study “really adds to the confidence we have in encouraging people to adopt the general heart-healthy diet approach, particularly with relation to fish and liquid vegetable oils,” Lichtenstein said, noting that fatty fish contains high levels of EPA and that soybean and canola oils, as well as walnuts, contain high levels of ALA.

If I was a clinician reading this paper, my take-home message would be that I should recommend eating food rich in omega-3 fatty acids, both marine and vegetable fatty acids, in STEMI patients to reduce adverse events during follow-up. Antoni Bayés-Genís

An accompanying editorial by Deepak Bhatt, MD (Brigham and Women’s Hospital, Boston, MA), and colleagues notes that it’s more efficient for the body to use EPA than ALA because it takes several steps to convert ALA.

But many people do not consume any animal products, and both Bayés-Genís and Lichtenstein said it doesn’t have to be an either/or situation when it comes to consuming omega-3s. “This is not a confrontation between them, because we found that they are partners in protection,” Bayés-Genís said. “The combination of the two is better. So I think that overall I would say that if you enrich your diet with two, three [servings of] marine fatty acids per week plus regularly eat nuts or seeds, that’s even better than just one or the other.”

When it comes to supplementation, the REDUCE-IT trial showed that a highly purified form of EPA, icosapent ethyl (Vascepa; Amarin), prevented CV events in statin-treated patients with high triglycerides, but strong data are lacking for the use of popular over-the-counter fish oil products.

For Lichtenstein, the focus is on adhering to an overall healthy dietary pattern rather than on introducing a single type of food. “If people are eating more fish as an entrée for lunch and dinner then it’s less likely that they’re going to be eating steak, hamburgers, or quiche, which are high in saturated fat,” she said. “In the same way, if people have higher levels of ALA, that means that they’re consuming foods that are prepared with soybean or canola oil, and maybe consuming walnuts, as opposed to foods that are prepared with things like butter and cream and eating snacks that are not high in the healthy long-chain unsaturated fatty acids.”

This study “confirms what we’ve been recommending all along, and this just adds additional strength to that recommendation,” she said.

Sticking to those recommendations might be even more important during the COVID-19 pandemic, Bayés-Genís said. “We need to do our best to stay healthy, and a good way to stay healthy is to enrich our cell membranes with omega-3 fatty acids to try to keep ourselves healthy and at home and to try to avoid having to see a doctor or visit an emergency room or a hospital.”