Online first
Current issue
Archive
Special Issues
About the Journal
Publication Ethics
Anti-Plagiarism system
Instructions for Authors
Instructions for Reviewers
Editorial Board
Editorial Office
Contact
Reviewers
All Reviewers
2023
2022
2021
2020
2019
2018
2017
2016
General Data Protection Regulation (RODO)
REVIEW PAPER
Current state-of-the-art knowledge on the role of omega-3 fatty acids in the prevention of cardiovascular disease
1
National Institute of Public Health -National Institute of Hygiene, Warsaw, Poland
2
Institute of Rural Health, Lublin, Poland
Corresponding author
Longina Kłosiewicz-Latoszek
National Institute of Public Health -National Institute of Hygiene, Powsińska, 61/63, 02-903, Warszawa, Poland
National Institute of Public Health -National Institute of Hygiene, Powsińska, 61/63, 02-903, Warszawa, Poland
Ann Agric Environ Med. 2020;27(4):519-525
KEYWORDS
cardiovascular disease preventionomega-3 fatty acidsmechanism of actionclinical trialsmetaanalysesEPAindications
TOPICS
Prevention of occupational diseases in agriculture, forestry, food industry and wood industryState of the health of rural communities depending on various factors: social factors, accessibility of medical care, etc.
ABSTRACT
Introduction:
Polyunsaturated n-3 fatty acid preparations containing eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA), or EPA only, have long been recommended in the management of hypertriglyceridaemia, especially when severe (triglyceride levels ≥500 mg/dL), at the dose of 2–4 g/d, mostly for the prevention of acute pancreatitis.
Material and Methods:
The presented article reviews clinical trials and their metaanalyses which evaluated the effect of n-3 fatty acids on cardiovascular disease risk, and regulatory agencies’ and cardiac societies’ positions regarding their use.
Results:
The findings indicate that only EPA is effective. Particular clinical benefit (25% reduction of cardiovascular events) was observed in the recently published REDUCE-IT trial which evaluated EPA (icosapent ethyl) at the dose of 4 g/d for 4.9 years (median), compared to placebo, in hypertriglycerydaemic patients at high or very high cardiovascular risk. This positive effect has been reflected in the expert opinions which recommend eicosapent ethyl (4 g/d) in patients similar to those participating in the REDUCE-IT trial. Additional data in favour of the above position have been provided by the EVAPORATE trial results which showed reduced progression of coronary atherosclerosis with EPA at the dose of 4 g/d.
Conclusions:
The clinical studies and metaanalyses strongly point out that only EPA (icosapent ethyl), especially at dose of 4 g/d, is effective in reducing cardiovascular events in very high and high risk patients with hypertriglyceridemia. The use of EPA + DHA preparations in doses up to 1 g/d does not prevent recurrent cardiovascular events.
Polyunsaturated n-3 fatty acid preparations containing eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA), or EPA only, have long been recommended in the management of hypertriglyceridaemia, especially when severe (triglyceride levels ≥500 mg/dL), at the dose of 2–4 g/d, mostly for the prevention of acute pancreatitis.
Material and Methods:
The presented article reviews clinical trials and their metaanalyses which evaluated the effect of n-3 fatty acids on cardiovascular disease risk, and regulatory agencies’ and cardiac societies’ positions regarding their use.
Results:
The findings indicate that only EPA is effective. Particular clinical benefit (25% reduction of cardiovascular events) was observed in the recently published REDUCE-IT trial which evaluated EPA (icosapent ethyl) at the dose of 4 g/d for 4.9 years (median), compared to placebo, in hypertriglycerydaemic patients at high or very high cardiovascular risk. This positive effect has been reflected in the expert opinions which recommend eicosapent ethyl (4 g/d) in patients similar to those participating in the REDUCE-IT trial. Additional data in favour of the above position have been provided by the EVAPORATE trial results which showed reduced progression of coronary atherosclerosis with EPA at the dose of 4 g/d.
Conclusions:
The clinical studies and metaanalyses strongly point out that only EPA (icosapent ethyl), especially at dose of 4 g/d, is effective in reducing cardiovascular events in very high and high risk patients with hypertriglyceridemia. The use of EPA + DHA preparations in doses up to 1 g/d does not prevent recurrent cardiovascular events.
Kłosiewicz-Latoszek L, Cybulska B, Tyszko P. Current state-of-the-art knowledge on the role of omega-3 fatty acids in the prevention of
cardiovascular disease. Ann Agric Environ Med. 2020; 27(4): 519–525. doi: 10.26444/aaem/126674
REFERENCES (66)
1.
Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with Icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019; 380: 11–22, doi: 10.1056/NEJMoa1812792.
2.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020; 41: 111–188. doi: 10.1093/eurheartj/ehz455.
3.
Skulas-Ray AC, Wilson PWF, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, et al. Omega-3 fatty acids of the management of hypertriglyceridemia: A Science Advisory from the American Heart Association. Circulation 2019; 140: 12, e673-e691. doi: 10.1161/CIR.0000000000000709.
4.
Orringer CE, Jacobson TA, Maki KC. National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCUD risk. J Clin Lipidol. 2019; 13(6): 860–872. doi: 10.1016/j.jacl.2019.10.014.
5.
Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello, et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: A science advisory from the American Heart Association. Circulation 2017; 135: e867–e884. doi: 10.1161/CIR.0000000000000482.
6.
American Diabetes Association; 2019. https://www.diabetes.org/newsr.... Accessed September 19, 2019.
7.
Zárate R, El Jaber-Vazdekis N, Tejera N, Perez JA, Rodriquez C. Significance of long chain polyunsaturated fatty acids in human health. Clin Transl Med. 2017; 6: 25. doi: 10.1186/s40169-017-0153-6.
8.
Watanabe Y, Tatsuno I. Prevention of cardiovascular events with omega-3 polyunsaturated fatty acids and the mechanizm involved. J Atheroscler Thromb. 2019; Oct 3. doi: 10.5551/jat.50658.
9.
Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: Effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011; 58: 2047–2067. doi: 10.1016/j.jacc.2011.06.063.
10.
Mozaffarian D, Prineas RJ, Stein PK, Siscovick DS. Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. J Am Coll Cardiol. 2006; 38: 478–484.
11.
Innes JK, Calder PC. The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiometabolic risk factors: a systematic review. Int J Mol Sci. 2018; 19(2): 532. doi: 10.3390/ijms19020532.
12.
Jacobson TA, Glickstein SB, Rove JD, Soni PR. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipid. 2012; 6: 5–18.
13.
Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011; 13: 474–483. doi: 10.1007/s11883-011-0210-3.
14.
Mozaffarian D, Wu JHY. (n-3) Fatty acids and cardiovascular health: are effects of EPA and DHA shared or a complementary? J Nutr. 2012; 142: 614S-625S.
15.
Musa-Veloso K, Binns MA, Kocenas AC, Poon T, Elliot JA, Rice H, et al. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid dose-dependentlyreduce fasting serum triglycerides. Nutr Rev. 2010; 68: 155–167. doi: 10.1111/j.1753-4887.2010.00272.x.
16.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014; 384: 626–635. doi: 10.1016/S0140-6736(14)61177-6.
17.
Sampson UK, Fazio S, Linton MRF. Residual car-diovascular risk despite optimal LDL cholesterol reduc-tion with statins: The evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep. 2012; 14: 1–10.
18.
Shearer GC, Savinova OV, Harris WS. Fish oil: how does it reduce plasma triglycerides? Biochim Biophys Acta. 2012; 1821: 843–851. doi: 0.1016/j.bbalip.2011.10.011.
19.
Kim CW, Addy C, Kusunoki J, Anderson NN, Deja S, Fu X, et al. Acetyl CoA carboxylase inhibition reduces hepatic steatosis but elevates plasma triglycerides in mice and humans: a bedside to bench investigation. Cell Metab. 2017; 26: 576. doi: 10.1016/j.cmet.2017.08.011.
20.
Pan M, Maitin V, Parathath S, Andreo U, Lin SX, St Germain C, et al. Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control. Proc Natl Acad Sci USA. 2008; 105: 5862–5867. doi: 10.1073/pnas.0707460104.
21.
Vors C, Couture P, Lamarche B. Omega-3 fatty acids: new insights into the impact of eicosapentaenoic and docosahexaenoic acids on lipid and lipoprotein. Curr Opin Lipidol. 2020; 31: 38–39. doi: 10.1097/MOL0000000000000660.
22.
Baum SJ, Scholz KP. Rounting the corner on residual risk: Implications of REDUCE-IT for omega-3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease. Clin Cardiol. 2019; 42: 829–838. doi: 10.1002/clc.23220.
23.
Jia X, Koh S, Al Rifai M, Blumenthal RS, Virani SS. Spotlight on icosapent ethyl for cardiovascular risk reduction: evidence to date. Vasc Health Risk Manag. 2020; 16: 1–10. doi: 10.2147/VHRM.S210149.
24.
Harris WS. Understanding why REDUCE-IT was positive – mechanistic overview of eicosapentaenoic acid. Prog Cardiovasc Dis. 2019; 62: 401–405. doi: 10.1016/j.pcad.2019.10.008.
25.
Jain AP, Aggarwal KK, Zhang PY. Omega-3 fatty acids and cardiovascular disease. Eur Rev Med Pharmacol Sci. 2015; 19(3): 441–445.
26.
Miller M, Ballantyne CM, Bays HE, Granowitz C, Doyle RT Jr, Juliano RA, et al. Effects of icocapent ethyl (eicosapentaenoic acid ethyl ester) on atherogenic lipid/lipoprotein, apolipoprotein, and inflammatory parameters in patients with elevated high-sensitivity C-Reactive Protein (from the ANCHOR Study). Am J Cardiol. 2019; 124(5): 696–701. doi: 10.1016/j.amjcard.2019.05.057.
27.
Brinton EA, Ballantyne CM, Bays HE, Kastelein JJ, Braeckman RA, Soni N. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study. Cardiovasc Diabetol. 2013; 12: 100. doi: 10.1186/1475-2840-12-100.
28.
Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. Icosapentethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013; 13: 37–46.
29.
Nelson JR, True WS, Le V, et al. Can pleiotropic effects of eicosapentaenoic acid (EPA) impast residua cardiovascular risk? Postgrad Med. 2017; 129: 822–827. doi: 10.1080/00325481.2017.1385365.
30.
Boden WE, Bhatt DL, Toth PP, Ray KK, Chapman MJ, Lüscher TF, et al. Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslpidaemia therapeutics. Eur Heart J. 2019; Dec 23. doi: 10.1093/eurheartj/ehz778.
31.
Nelson JR, Wani O, May HT, Budoff M. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques. Vascul Pharmacol. 2017; 99: 1–9. doi: 10.1016/j.vph.2017.02.004.
32.
Budoff M, Muhlestein BJ, Le VT, et al. Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200–499 mg/dl) on statin therapy: rationale and design of the EVAPORATE Study. Clin Cardiol. 2018; 41: 13–19.
34.
Watanabe T, Ando K, Daidoji H, Otaki Y, Sugawara S, Matsui M, et al. CHERRY Study Investigators. A randomized controlled trial of eicosapentenoic acid in patients with coronary heart disease on statins. J Cardiol. 2017; 70: 537–544.
35.
DINIcolantonio JJ, O’Keefe JH. The benefits of Marine omega – 3s for the prevention and treatment of cardiovascular disease. Missouri Med. 2019; 116(5): 404–408.
36.
Bang HO, Dyerberg J, Nielson AB. Plasma lipid and lipoprotein pat tern in Greenlandic West-coast Eskimos. Lancet 1971; 1: 1143–1145.
37.
Tani S, Matsuo R, Imatake K, Suzuki Y, Takahashi A, Matsumoto N. Association of daily fish intake with serum non-high-density lipoprotein cholesterol levels and healthy lifestyle behaviours in apparently healthy males over the age of 50 years in Japanese: Implication for the anti-atherosclerotic effect of fish consumption. Nutr Metab Cardiovasc Dis. 2020 Feb 10; 30(2): 190–200. doi: 10.1016/j.numecd.2019.09.019.
38.
Marchioli R. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet 1999; 354: 447–455.
39.
Yokoyama M, Origasa H, Matsuzaki M, et al. Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis. Lancet 2007; 369: 1090–1098.
40.
Nosaka K, Miyoshi T, Iwamoto M, Kajiya M, Okawa K, Tsukuda S, et al. Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomesth an statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study. Int J Cardiol. 2017; 228: 173–9.
42.
Budoff MJ, Muhlestein JB, Bhatt DL, Le Pa VT, May HT, et al. Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients with Elevated Triglycerides on Statin Therapy: A prospective, placebo-controlled randomized trial (EVAPORATE): Interim Results Cardiovasc Res. 2020 Jul 1: cvaa184. doi: 10.1093/cvr/cvaa184.
43.
Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH SJ, et al. Assessment of omega-3carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: rationaleand design of the STRENGTH trial. Clin Cardiol. 2018; 41(10): 1281–1288. doi: 10.1002/clc.23055.
44.
UMIN-CTR Clinical Trial. Randomized trial for evaluation in secondary prevention efficacy of combination therapy — statin and eicosapentaenoic acid UMIN000012069; 2018. Available from:https://upload.umin.ac.jp/cgi-.... Accessed November 22, 2019.
45.
Laake K, Myhre P, Nordby LM, et al. Effects of ?3 supplementation in elderly patients with acute myocardial infarction: design of a prospective randomized placebo controlled study. BMC Geriatr. 2014; 14: 74. doi: 10.1186/1471-2318-14-74r.
46.
Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019; 380: 23–32. doi: 10.1056/NEJMoa1811403.
47.
The Ascend Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018; 379(16): 1540–1550.
48.
Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation. 2010; 122: 2152–9.
49.
Einvik G, Ole Klemsdal T, Sandvik L, Hjerkinn EM. A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk. Eur J Prev Cardiol. 2010; 17: 588–92.
50.
ORIGIN Trial Investigators, Bosch J, Gerstein HC, Dagenais GR, Díaz R, Dyal L, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012; 367: 309–18.
51.
Macchia A, Grancelli H, Varini S, Nul D, Laffaye N, Mariani J, et al.Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial J Am Coll Cardiol. 2013 Jan 29; 61(4): 463–468. doi: 10.1016/j.jacc.2012.11.021.
52.
Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, et al. n-3 fatty acidsin patients with multiple cardiovascular risk factors. N Engl J Med. 2013; 368: 1800–8.
53.
Writing Group for the AREDS2 Research Group, Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, et al. Effect of long-chain ?-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014; 174: 763–71.
55.
Alexander DD, Miller PE, Van Elswyk ME, Kuratko CN, Bylsma LC. A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk. Mayo Clin Proc. 2017; 92: 15–29. doi: 10.1016/j.mayocp.2016.10.018.
56.
Maki KC, Palacios OM, Bell M, Toth PP. Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps. J Clin Lipidol. 2017; 11: 1152–1160. doi: 10.1016/j.jacl.2017.07.010.
57.
Hooper L, Abdelhamid A, Ajabnoor S, Brainard J, Brown T, Hanson, et al. World Health Organization; et al. Set of Systematic Reviews of RCTs on the Health Effects of Omega 3 Polyunsaturated Fats in Adults. Available online: http://www.iffo.net/system/fil....
58.
Aung T, Halsey J, Kromhout D, Gerstein H.C, Marchioli R, Tavazzi L, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: Meta-analysis of 10 trials involving 77,917 individuals. JAMA Cardiol. 2018; 3: 224–234. doi: 10.1001/jamacardio.2017.5205.
59.
Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC , Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018 Nov 30; 11: CD003177. doi: 10.1002/14651858.CD00317.
60.
Marston NA, Giugliano RP, Im K, Silverman MG, O’Donoghue ML, Wiviott SD, Ference BA, Sabatine MS. Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials. Circulation. 2019 Oct 15; 140(16): 1308–1317. doi: 10.1161/CIRCULATIONAHA.119.041998.
61.
Casula M, Olmastroni E, Gazzotti M, Galimberti F, Zambon A, Catapano AL. Omega-3 polyunsaturated fatty acids supplementation and cardiovascular outcomes: do formulation, dosage, and baseline cardiovascular risk matter? An updated meta-analysis of randomized controlled trias. Pharmacol Res. 2020 Jul 4; 160: 105060. doi: 10.1016/j.phrs.2020.105060.
63.
Lombardi M, Chiabrando JG, Vescovo GM, Bressi E, Del Buono MG, Carbone S, et al. Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis Curr Atheroscler Rep. 2020 Jul 16; 22(9): 45. doi: 10.1007/s11883-020-00865-5.
64.
Hilleman DE, Wiggins BS, Bottorff MB. Critical differences between dietary supplement and prescription omega-3 fatty acids: a narrative review. Adv Ther. 2020; 37(2): 656–670. doi: 10.1007/s12325-019-01211-1.
65.
Chen C, Yu X, Shao S. Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS One. 2015; 10: e0139565. doi: 10.1371/journal.pone.0139565.
66.
Rimm EB, Appel LJ, Chiuve SE, Djoussé L, Engler MB, Kris-Etherton PM, et al. American Heart Association Nutrition Committee on the Council on Lifestyle and Cardiometabolic Health; et al. Seafood long-chain n-3 polyunsaturated fatty acids andcardiovascular disease: A science advisory from the American Heart Association. Circulation 2018; 138(1): e35-e47. doi: 10.1161/CIR.0000000000000574.
Share
RELATED ARTICLE
| eISSN: | 1898-2263 |
| ISSN: | 1232-1966 |
Improvement of visual identification of the journal - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher Education allocated to the activities of disseminating science.
Generation of the DOI (Digital Object Identifier) - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher
© 2006-2024 Journal hosting platform by Bentus
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
