Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Lipids and cardiovascular/metabolic health

Early-onset coronary atherosclerosis in patients with low levels of omega-3 fatty acids

Abstract

Objectives

Coronary artery calcification (CAC) can reliably predict cardiovascular events. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to inhibit vascular calcification on a cellular level and in animal models, however, the correlation in humans is controversial.

Methods

In symptomatic patients, CAC was quantified according to Agatstons’ method using non-contrast coronary CT. We assessed the association of EPA and DHA with early-onset coronary atherosclerosis, defined as presence of CAC above the 75th Agatston-Score (AS) percentile in sex adjusted age categories. Erythrocyte fatty acid composition was analyzed with a standardized methodology. The percentage of EPA and DHA in relation to all fatty acids present in the erythrocyte membrane is regarded the Omega-3 Index®.

Results

Among 71 patients, 51 were below and 20 were above the 75th AS-percentile. No differences were seen in age, gender, cardiovascular risk factors, and relevant medication. In univariable analysis, significantly lower values for EPA (0.77%[0.63; 0.97] vs. 0.93%[0.72; 1.21]; p = 0.045), DHA (4.90%[4.12; 5.57] vs. 5.50%[4.58; 6.52]; p = 0.038) and the Omega-3 Index (5.73%[4.75; 6.35] vs. 6.22%[5.46; 7.71]; p = 0.034) were seen in patients above the 75th AS-percentile. All other fatty acids showed no significant differences. In multivariable analysis, the Omega-3 Index showed a significant inverse association with early onset of CAC (OR: 0.533 (95%CI: 0.303–0.938; p = 0.029)), independent of age, gender, statin use, and creatinine level (all p > 0.05).

Conclusions

Low levels of EPA and DHA (Omega-3 Index) are associated with early-onset coronary atherosclerosis. This finding needs to be validated in larger cohorts and might help understand the beneficial cardiovascular effects of omega-3 fatty acids.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Gas chromatographically quantification of erythrocyte fatty acid composition.

Similar content being viewed by others

References

  1. Burr ML, Sweetham PM, Fehily AM. Diet and reinfarction. Eur Heart J. 1994;15:1152–3.

    Article  CAS  Google Scholar 

  2. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999;354:447–55.

  3. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090–8.

    Article  CAS  Google Scholar 

  4. Harris WS, Tintle NL, Etherton MR, Vasan RS. Erythrocyte long-chain omega-3 fatty acid levels are inversely associated with mortality and with incident cardiovascular disease: The Framingham Heart Study. J Clin Lipido. 2018;12:718–27 e6.

    Article  Google Scholar 

  5. Kleber ME, Delgado GE, Lorkowski S, Marz W, von Schacky C. Omega-3 fatty acids and mortality in patients referred for coronary angiography. The Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis. 2016;252:175–81.

    Article  CAS  Google Scholar 

  6. 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. 2018.

  7. Abedin M, Lim J, Tang TB, Park D, Demer LL, Tintut Y. N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways. Circ Res. 2006;98:727–9.

    Article  CAS  Google Scholar 

  8. Schlemmer CK, Coetzer H, Claassen N, Kruger MC, Rademeyer C, van Jaarsveld L, et al. Ectopic calcification of rat aortas and kidneys is reduced with n-3 fatty acid supplementation. Prostaglandins Leukot Ess Fat Acids. 1998;59:221–7.

    Article  CAS  Google Scholar 

  9. Bittner DO, Mayrhofer T, Bamberg F, Hallett TR, Janjua S, Addison D, et al. Impact of coronary calcification on clinical management in patients with acute chest pain. Circ Cardiovasc Imaging. 2017;10:e005893.

    Article  Google Scholar 

  10. Bittner DO, Takx RAP, Staziaki PV, Janjua S, Neilan TG, Meyersohn NM, et al. Predictive value of coronary artery calcification and TIMI risk score in the assessment of patients with acute chest pain: results from an ED registry. J Am Coll Cardiol. 2016; 67:515.

    Article  Google Scholar 

  11. Blaha M, Budoff MJ, Shaw LJ, Khosa F, Rumberger JA, Berman D, et al. Absence of coronary artery calcification and all-cause mortality. JACC Cardiovasc Imaging. 2009;2:692–700.

    Article  Google Scholar 

  12. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860–70.

    Article  Google Scholar 

  13. Budoff MJ, Young R, Burke G, Jeffrey Carr J, Detrano RC, Folsom AR, et al. Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA). Eur Heart J. 2018;39:2401–8.

    Article  CAS  Google Scholar 

  14. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr., Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827–32.

    Article  CAS  Google Scholar 

  15. Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39:212–20.

    Article  CAS  Google Scholar 

  16. Sands SA, Reid KJ, Windsor SL, Harris WS. The impact of age, body mass index, and fish intake on the EPA and DHA content of human erythrocytes. Lipids. 2005;40:343–7.

    Article  CAS  Google Scholar 

  17. Niki T, Wakatsuki T, Yamaguchi K, Taketani Y, Oeduka H, Kusunose K, et al. Effects of the addition of eicosapentaenoic acid to strong statin therapy on inflammatory cytokines and coronary plaque components assessed by integrated backscatter intravascular ultrasound. Circ J. 2016;80:450–60.

    Article  CAS  Google Scholar 

  18. Nelson JR, Wani O, May HT, Budoff M. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques. Vasc Pharmacol. 2017;91:1–9.

    Article  CAS  Google Scholar 

  19. Sekikawa A, Mahajan H, Kadowaki S, Hisamatsu T, Miyagawa N, Fujiyoshi A, et al. Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men. Eur J Clin Nutr. 2019;73:783–92.

    Article  CAS  Google Scholar 

  20. Sekikawa A, Miura K, Lee S, Fujiyoshi A, Edmundowicz D, Kadowaki T, et al. Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: population based prospective cohort study. Heart 2014;100:569–73.

    Article  CAS  Google Scholar 

  21. Budoff M, Brent Muhlestein J, Le VT, May HT, Roy S, Nelson JR. 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;41:13–9.

    Article  Google Scholar 

  22. Puri R, Nicholls SJ, Shao M, Kataoka Y, Uno K, Kapadia SR, et al. Impact of statins on serial coronary calcification during atheroma progression and regression. J Am Coll Cardiol. 2015;65:1273–82.

    Article  CAS  Google Scholar 

  23. Harris WS, Kennedy KF, O'Keefe JH Jr., Spertus JA. Red blood cell fatty acid levels improve GRACE score prediction of 2-yr mortality in patients with myocardial infarction. Int J Cardiol. 2013;168:53–9.

    Article  Google Scholar 

  24. Iwamatsu K, Abe S, Nishida H, Kageyama M, Nasuno T, Sakuma M, et al. Which has the stronger impact on coronary artery disease, eicosapentaenoic acid or docosahexaenoic acid? Hypertens Res. 2016;39:272–5.

    Article  CAS  Google Scholar 

  25. von Schacky C. Omega-3 index and cardiovascular health. Nutrients. 2014;6:799–814.

    Article  Google Scholar 

  26. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9.

    Article  CAS  Google Scholar 

  27. Flock MR, Skulas-Ray AC, Harris WS, Etherton TD, Fleming JA, Kris-Etherton PM. Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J Am Heart Assoc. 2013;2:e000513.

    Article  Google Scholar 

  28. Köhler A, Bittner D, Löw A, von Schacky C. Effects of a convenience drink fortified with n-3 fatty acids on the n-3 index. Br J Nutr. 2010;104:729–36.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. O. Bittner.

Ethics declarations

Conflict of interest

MM reports honoraria from Siemens HealthCare and Edwards Lifescience outside the submitted work, and YZ reports lecture fees from Baxter, MSD and Shire outside the submitted work. The other authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bittner, D.O., Goeller, M., Zopf, Y. et al. Early-onset coronary atherosclerosis in patients with low levels of omega-3 fatty acids. Eur J Clin Nutr 74, 651–656 (2020). https://doi.org/10.1038/s41430-019-0551-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-019-0551-5

This article is cited by

Search

Quick links