STEMI Patients Fare Better With Higher Circulating Levels of Omega-3 Fatty Acids

Patients with ST-elevation acute myocardial infarction (STEMI) who had high circulating levels of omega-3 fatty acids—both eicosapentaenoic acid (EPA) and alpha-linolenic acid (ALA)—were more likely to survive and less likely to have a recurrent heart attack, according to findings from a study of 944 STEMI patients.

The observation is particularly interesting because unlike fish-derived EPA, ALA has many plant sources including flax seed, walnuts, soy products, and canola oil, which makes it attractive to those who have seafood allergies, or whose religious or dietary preferences limit consumption of fish.

Writing in the Journal of the American College of Cardiology, Iolanda Lázaro, PhD, of the Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, in Madrid, and colleagues reported that “serum-phosphatidylcholine [PC] EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]:0.62-0.94, and HR: 0.74; 95% CI: 0.58-0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44-0.96, for a 1-SD increase).”

Those results, Lázaro et al wrote, not only support the notion that dietary consumption of foods rich in omega-3 fatty acids can benefit the cardiovascular system, but may “also explain, in part, the paradoxical observation that countries with customarily high seafood intake, such as Japan and Spain, have lower CAD mortality rates, despite a high prevalence of CV risk factors.”

In an accompanying editorial, Harvard’s Deepak L. Bhatt, MD, MPH, along with Matthew J. Budoff, MD ,of Harbor-UCLA Medical Center and R. Preston Mason, PhD, of Elucida Research in Beverly, Massachusetts, praised the study by Lázaro et al and said that although the study was limited to STEMI patients, the findings can reasonably be extended to all patients with atherosclerosis, as well as those who are at risk for developing it.

“For those with fish or seafood allergy, or who for religious or ethical reasons are vegetarian or vegan and extend this to prohibit consumption of marine derived products, ALA may provide a suitable alternative,” Bhatt et al wrote.

That said, the editorialists had some caveats, noting that “the conversion of ALA to EPA is very inefficient with a rate of only approximately 5% to 20%, with higher, estrogen-dependent rates only among healthy younger women. Thus, ALA may not be a sufficient substitute for direct dietary sources of EPA and related long chain fatty acids.”

But taken as a whole, Bhatt et al wrote that the study by Lázaro and colleagues provided not only “implications for drug development” but also lesson that can be applied in dietary guidance. They added that “based on findings such as from Lázaro et al it makes sense to counsel patients to increase their intake of foods rich in OM3FAs such as EPA and ALA in place of less healthy sources of calories, as well as to implement use of prescription EPA in patients who have approved indications.”

Among the 944 who had samples included in the analysis, the median age was 61 and 22% (n=209) were women. During follow-up, “211 patients had MACE, 108 died, and 130 were readmitted for [cardiovascular] causes.”

“Compared with subjects in the lowest tertile of EPA (cutoff<0.366% of all the fatty acids in serum-PC),those in the highest EPA tertile (≥0.592% of all the fatty acids in the serum-PC) had significantly reduced risks of incident CV readmission and incident MACE. When we explored ALA as exposure, subjects in the lowest ALA tertile (<0.134%of all the fatty acids in serum-PC) had a significantly increased risk of incident all-cause mortality, compared with those in the intermediate and highest ALA tertiles,” Lázaro et al wrote.

The study was observational, and as a result the researchers could not “determine whether the consumption of dietary EPA and ALA intakes before STEMI actually improve the long-term prognosis.” Additionally, “the fatty acids in serum-PC do not reflect long-term intake as accurately as the fatty acids harbored in adipose tissue or red blood cells. Finally, dietary data other than fatty acids and some potential confounding variables like socioeconomic status, education, and pharmacologic treatments at baseline and during follow-up were not available; therefore, we could not exclude the possibility that health-related variables that may covary with omega-3 fatty acids might have affected the studied outcomes.”

1. In patients with ST-elevation MI, higher circulating levels of EPA and ALA, which reflect dietary intake of omega-3 fatty acids, are associated with a more favorable prognosis.

2. Further research is needed to establish dietary approaches to optimizing EPA and ALA intake for individuals at risk of developing acute MI as well as for survivors of MI.

Peggy Peck, Editor-in-Chief, BreakingMED™

Lázaro had no disclosures.

Bhatt served as the Chair and International Principal Investigator for REDUCE-IT, with research funding from Amarin to Brigham and Women’s Hospital; has served on the Advisory Board for Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; has served on the Board of Directors of Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA CART Research and Publications Committee; has served on data monitoring committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack

Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as Deputy Editor of Clinical Cardiology; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as site co-investigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; has served as a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda.

Budoff received grant support from and served on the Speakers Bureau of Amarin.

Mason received consulting and research grants from Amarin Pharma, Novartis, and Pfizer; and has served on the Advisory Board of Cardax.

Cat ID: 102

Topic ID: 74,102,102,305,4,446,5,914,192,94,917,925