Plasma Omega-3 Polyunsaturated Fatty Acids and Survival in Patients with Chronic Heart Failure and Major Depressive Disorder

  • Wei JiangEmail author
  • Harry Oken
  • Mona Fiuzat
  • Linda K. Shaw
  • Carolyn Martsberger
  • Maragatha Kuchibhatla
  • Rima Kaddurah-Daouk
  • David C. Steffens
  • Rebecca Baillie
  • Michael Cuffe
  • Ranga Krishnan
  • Christopher O’Connor
  • for the SADHART-CHF Investigators


The omega-3 fatty acid (FA) concentration is low in patients with coronary heart disease (CHD). Supplement of omega-3 FA improves cardiovascular outcomes in patients with CHD and heart failure (HF). However, plasma omega-3 FA and its role for prognosis in HF patients have not been examined previously. In this study, we explore the prognostic value of omega-3 polyunsaturated FA in HF patients with major depressive disorder (MDD). Plasma was obtained from HF patients with MDD who participated in the Sertraline Against Depression and Heart Disease in Chronic Heart Failure trial. FA methyl esters were analyzed by the method of a flame ionization detector. Weight percent is the unit of the omega compounds. The primary outcome was survival which was analyzed using Cox proportional hazards regression modeling. A total of 109 depressed HF patients had adequate volume for completion of the FA assays. Plasma total omega-3 (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.43–0.98) and EPA_0.1 unit (HR 0.73, 95% CI 0.56–0.96) were significantly associated with survival of patients with HF and co-morbid MDD. The results suggest that low plasma omega-3 FA is a significant factor for reduced survival in HF patients with MDD.


Omega-3 fatty acids Heart failure Depression Prognosis 



The authors would like to thank Eileen Bailey-Hall of Martek Biosciences Corporation, Columbia, MD and the Martek Biosciences Corporation for the significant contribution in regards to processing plasma samples and the FA analysis. We would also like to thank Dr. Steve Rozen of the Duke-NUS Graduate Medical School Singapore in Singapore for his contribution of data analysis and interpretation.

Funding Sources

The study was funded by the SADHART-CHF study (R01-MH063211) and R21 MH076178 by the National Institute of Mental Health (NIMH) Bethesda, Maryland.

Financial Disclosures

• Dr. Jiang received salary support through the NIMH research grant, and a minority supplement award for the biomarker study affiliated to the SADHART-CHF grant.

• Dr. O'Connor has received salary support through the NIMH research grant and is a consultant for Martek Biosciences Corporation.

• Dr. Kuchibhatla received salary support through the NIMH research grant.

• Dr. Cuffe has received salary support through the NIMH research grant.

• Dr. Krishnan has received salary support through the NIMH research grant.

• Dr. Martsberger has received salary support from the NIMH research grant.

• Linda Shaw: nothing to disclose for this study.

• Dr. Fiuzat: nothing to disclose for this study.

• Dr. Oken is a consultant to the Martek Biosciences Corporation.

• Dr. Kaddurah-Daouk: nothing to disclose for this study.

• Dr. Steffens has received salary support from NIMH for the metabolomic study.

• Dr. Baillie: nothing to disclose for this study.

All authors had access to the data. The preliminary result of the omega fatty acid study was presented at the 2010 American College of Cardiology Annual Meeting in March 2010 in Atlanta, GA.


  1. 1.
    Albert, C. M., Hennekens, C. H., O'Donnell, C. J., et al. (1998). Fish consumption and risk of sudden cardiac death. Journal of the American Medical Association, 279(1), 23–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Kromhout, D., Bosschieter, E. B., & Coulander, C. D. (1985). The inverse relation between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine, 312(19), 1205–1209.PubMedCrossRefGoogle Scholar
  3. 3.
    Lavie, C. J., & Milani, R. V. (1996). Fish oils. In F. H. Messerli (Ed.), Cardiovascular drug therapy (pp. 1608–1613). Philadelphia: Saunders.Google Scholar
  4. 4.
    Lee, J. H., O'Keefe, J. H., Lavie, C. J., Marchioli, R., & Harris, W. S. (2008). Omega-3 fatty acids for cardioprotection. Mayo Clinic Proceedings, 83(3), 324–332.PubMedCrossRefGoogle Scholar
  5. 5.
    Yokoyama, M., Origasa, H., Matsuzaki, M., et al. (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised openlabel, blinded endpoint analysis. Lancet, 369(9567), 1090–1098.PubMedCrossRefGoogle Scholar
  6. 6.
    Valagussa, F., Franzosi, M. G., Geraci, E., et al. (1999). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet, 354(9177), 447–455.CrossRefGoogle Scholar
  7. 7.
    Harris, W. S., Mozaffarian, D., Rimm, E., et al. (2009). Omega-6 fatty acids and risk for cardiovascular disease a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation, 119(6), 902–907. doi: 10.1161/circulationaha.108.191627.PubMedCrossRefGoogle Scholar
  8. 8.
    Kris-Etherton, P. M., Harris, W. S., Appel, L. J., & Nutr, C. (2003). Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arteriosclerosis Thrombosis and Vascular Biology, 23(2), E20–E31. doi: 10.1161/01.atv.0000038493.65177.94.CrossRefGoogle Scholar
  9. 9.
    Lichtenstein, A. H., Appel, L. J., Brands, M., et al. (2006). Diet and lifestyle recommendations revision 2006—A scientific statement from the American Heart Association Nutrition Committee. Circulation, 114(1), 82. doi: 10.1161/circulationaha.106.176158.PubMedCrossRefGoogle Scholar
  10. 10.
    Tavazzi, L., Maggioni, A. P., Marchioli, R., et al. (2008). Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): A randomised, double-blind, placebo-controlled trial. Lancet, 372(9645), 1223–1230. doi: 10.1016/s0140-6736(08)61239-8.PubMedCrossRefGoogle Scholar
  11. 11.
    Jiang, W., O'Connor, C., Silva, S. G., et al. (2008). Safety and efficacy of sertraline for depression in patients with CHF (SADHART-CHF): A randomized, double-blind, placebo-controlled trial of sertraline for major depression with congestive heart failure. American Heart Journal, 156(3), 437–444. doi: 10.1016/j.ahj.2008.05.003.PubMedCrossRefGoogle Scholar
  12. 12.
    O'Connor, C. M., Jiang, W., Kuchibhatla, M., et al. (2010). Safety and efficacy of sertraline for depression in patients with heart failure: Results of the SADHART-CHF trial. Journal of the American College of Cardiology, 56(9), 692–699.PubMedCrossRefGoogle Scholar
  13. 13.
    Beck, A. T., Steer, R. A., Ball, R., & Ranieri, W. F. (1996). Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. Journal of Personality Assessment, 67(3), 588–597.PubMedCrossRefGoogle Scholar
  14. 14.
    Bailey-Hall, E., Nelson, E. B., & Ryan, A. S. (2008). Validation of a rapid measure of blood PUFA levels in humans. Lipids, 43(2), 181–186. doi: 10.1007/s11745-007-3140-7.PubMedCrossRefGoogle Scholar
  15. 15.
    Lands, W. E. M. (2003). Functional foods in primary prevention or nutraceuticals in secondary prevention? Current Topics in Nutraceutical Research, 1, 113–119.Google Scholar
  16. 16.
    Paganelli, F., Maixent, J. M., Duran, M. J., Parhizgar, R., Pieroni, G., & Sennoune, S. (2001). Altered erythrocyte n-3 fatty acids in Mediterranean patients with coronary artery disease. Int J Cardiol, 78(1), 27–32.PubMedCrossRefGoogle Scholar
  17. 17.
    Rissanen, T., Voutilainen, S., Nyyssonen, K., Lakka, T. A., & Salonen, J. T. (2000). Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events—the Kuopio Ischaemic Heart Disease Risk Factor Study. Circulation, 102(22), 2677–2679.PubMedGoogle Scholar
  18. 18.
    Rupp, H., Wagner, D., Rupp, T., Schulte, L. M., & Maisch, B. (2004). Risk stratification by the “EPA + DHA level” and the “EPA/AA ratio”—Focus on anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids. Herz, 29(7), 673–685. doi: 10.1007/s00059-004-2602-4.PubMedCrossRefGoogle Scholar
  19. 19.
    Siscovick, D. S., Raghunathan, T. E., King, I., et al. (1995). Dietary-intake and cell-membrane levels of long-chain n-3 polyunsaturated fatty-acids and the risk of primary cardiac-arrest. JAMA: The Journal of the American Medical Association, 274(17), 1363–1367.CrossRefGoogle Scholar
  20. 20.
    Harris, W. S., Poston, W. C., & Haddock, C. K. (2007). Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis, 193(1), 1–10. doi: 10.1016/j.atherosclerosis.2007.03.018.PubMedCrossRefGoogle Scholar
  21. 21.
    Mori, T. A., & Woodman, R. J. (2006). The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Current Opinion in Clinical Nutrition and Metabolic Care, 9(2), 95–104.PubMedCrossRefGoogle Scholar
  22. 22.
    Wilhelm, M., Tobias, R., Asskali, F., et al. (2008). Red blood cell omega-3 fatty acids and the risk of ventricular arrhythmias in patients with heart failure. American Heart Journal, 155(6), 971–977. doi: 10.1016/j.ahj.2007.11.045.PubMedCrossRefGoogle Scholar
  23. 23.
    Frasure-Smith, N., Lesperance, F., & Julien, P. (2004). Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Biological Psychiatry, 55(9), 891–896. doi: 10.1016/j.biopsych.2004.01.021S0006322304001076.PubMedCrossRefGoogle Scholar
  24. 24.
    Peet, M., Murphy, B., Shay, J., & Horrobin, D. (1998). Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biological Psychiatry, 43(5), 315–319.PubMedCrossRefGoogle Scholar
  25. 25.
    Edwards, R., Peet, M., Shay, J., & Horrobin, D. (1998). Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. Journal of Affective Disorders, 48(2–3), 149–155.PubMedCrossRefGoogle Scholar
  26. 26.
    Maes, M., Christophe, A., Delanghe, J., Altamura, C., Neels, H., & Meltzer, H. Y. (1999). Lowered omega 3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Research, 85(3), 275–291.PubMedCrossRefGoogle Scholar
  27. 27.
    Mamalakis, G., Jansen, E., Cremers, H., Kiriakakis, M., Tsibinos, G., & Kafatos, A. (2006). Depression and adipose and serum cholesteryl ester polyunsaturated fatty acids in the survivors of the seven countries study population of Crete. European Journal of Clinical Nutrition, 60(8), 1016–1023. doi: 10.1038/sj.ejcn.1602413.PubMedCrossRefGoogle Scholar
  28. 28.
    McNamara, R. K., Hahn, C. G., Jandacek, R., et al. (2007). Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biological Psychiatry, 62(1), 17–24. doi: 10.1016/j.biopsych.2006.08.026.PubMedCrossRefGoogle Scholar
  29. 29.
    Maes, M., Smith, R., Christophe, A., Cosyns, P., Desnyder, R., & Meltzer, H. (1996). Fatty acid composition in major depression: Decreased omega 3 fractions in cholesteryl esters and increased C20:4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. Journal of Affective Disorders, 38(1), 35–46.PubMedCrossRefGoogle Scholar
  30. 30.
    Tiemeier, H., van Tuijl, H. R., Hofman, A., Kiliaan, A. J., & Breteler, M. M. B. (2003). Plasma fatty acid composition and depression are associated in the elderly: The Rotterdam Study. American Journal of Clinical Nutrition, 78(1), 40–46.PubMedGoogle Scholar
  31. 31.
    Feart, C., Peuchant, E., Letenneur, L., et al. (2008). Plasma eicosapentaenoic acid is inversely associated with severity of depressive symptomatology in the elderly: Data from the Bordeaux sample of the Three-City Study. American Journal of Clinical Nutrition, 87(5), 1156–1162.PubMedGoogle Scholar
  32. 32.
    Tang, W. H. W., & Samara, M. A. (2011). Polyunsaturated Fatty acids in heart failure: Should we give more and give earlier? Journal of the American College of Cardiology, 57(7), 880–883.PubMedCrossRefGoogle Scholar
  33. 33.
    Calder, P. C. (1998). Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Brazilian Journal of Medical and Biological Research, 31(4), 467–490.PubMedCrossRefGoogle Scholar
  34. 34.
    Heller, A. T. J., & Koch, T. (2003). Fish or chips? News in Physiological Sciences, 18, 50–54.PubMedGoogle Scholar
  35. 35.
    Simopoulos, A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy, 56(8), 365–379.CrossRefGoogle Scholar
  36. 36.
    Christensen, J. H., Christensen, M. S., Dyerberg, J., & Schmidt, E. B. (1999). Heart rate variability and fatty acid content of blood cell membranes: A dose-response study with n-3 fatty acids. American Journal of Clinical Nutrition, 70(3), 331–337.PubMedGoogle Scholar
  37. 37.
    Ghio, S., Scelsi, L., Latini, R., et al. (2010). Effects of n-3 polyunsaturated fatty acids and of rosuvastatin on left ventricular function in chronic heart failure: A substudy of GISSI-HF trial. European Journal of Heart Failure: Journal of the Working Group on Heart Failure of the European Society of Cardiology, 12(12), 1345–1353.Google Scholar
  38. 38.
    Nodari, S., Triggiani, M., Campia, U., et al. (2011). Effects of n-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy. Journal of the American College of Cardiology, 57(7), 870–879.PubMedCrossRefGoogle Scholar
  39. 39.
    Lin, P. Y., & Su, K. P. (2007). A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. The Journal of Clinical Psychiatry, 68(7), 1056–1061.PubMedCrossRefGoogle Scholar
  40. 40.
    Richardson, A. J. (2008). n-3 fatty acids and mood: The devil is in the detail. British Journal of Nutrition, 99(2), 221–223. doi: 10.1017/s0007114507824123.PubMedCrossRefGoogle Scholar
  41. 41.
    Ross, B. M. (2008). The emerging role of eicosapentaenoic acid as an important psychoactive natural product: Some answers but a lot more questions. Lipid Insights, 2, 98–7.Google Scholar
  42. 42.
    Burdge, G. C., & Wootton, S. A. (2002). Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. British Journal of Nutrition, 88(4), 411–420. doi: 10.1079/bjn2002689.PubMedCrossRefGoogle Scholar
  43. 43.
    Burdge, G. C., & Calder, P. C. (2005). Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reproduction Nutrition Development, 45(5), 581–597. doi: 10.1051/rnd:2005047.CrossRefGoogle Scholar
  44. 44.
    Burdge, G. C., Jones, A. E., & Wootton, S. A. (2002). Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men. British Journal of Nutrition, 88(4), 355–363. doi: 10.1079/bjn2002662.PubMedCrossRefGoogle Scholar
  45. 45.
    Arterburn, L. M., Hall, E. B., & Oken, H. (2006). Distribution, interconversion, and dose response of n-3 fatty acids in humans. American Journal of Clinical Nutrition, 83(6), 1467S–1476S.PubMedGoogle Scholar
  46. 46.
    Cho, H. P., Nakamura, M., & Clarke, S. D. (1999). Cloning, expression, and fatty acid regulation of the human delta-5 desaturase. Journal of Biological Chemistry, 274(52), 37335–37339.PubMedCrossRefGoogle Scholar
  47. 47.
    Xie LaI, S. M. (2010). Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study. Journal of Nutrigenetics and Nutrigenomics, 2(4–5), 243–250.Google Scholar
  48. 48.
    Lalovic, A., Klempan, T., Sequeira, A., Luheshi, G., & Turecki, G. (2010). Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers. Journal of Affective Disorders, 120(1–3), 24–31. doi: 10.1016/j.jad.2009.04.007.PubMedCrossRefGoogle Scholar
  49. 49.
    BoltonSmith, C., Woodward, M., & Tavendale, R. (1997). Evidence for age-related differences in the fatty acid composition of human adipose tissue, independent of diet. European Journal of Clinical Nutrition, 51(9), 619–624.CrossRefGoogle Scholar
  50. 50.
    Bordoni, A., Biagi, P. L., Turchetto, E., & Hrelia, S. (1988). Aging influence on delta-6-desaturase activity and fatty-acid composition of rat-liver microsomes. Biochemistry International, 17(6), 1001–1009.PubMedGoogle Scholar
  51. 51.
    Bourre, J. M., & Piciotti, M. (1997). Alterations in eighteen-carbon saturated, monounsaturated and polyunsaturated fatty acid peroxisomal oxidation in mouse brain during development and aging. Biochemistry and Molecular Biology International, 41(3), 461–468.PubMedGoogle Scholar
  52. 52.
    Hrelia, S., Bordoni, A., Celadon, M., Turchetto, E., Biagi, P. L., & Rossi, C. A. (1989). Age-related-changes in linoleate and alpha-linolenate desaturation by rat-liver microsomes. Biochemical and Biophysical Research Communications, 163(1), 348–355.PubMedCrossRefGoogle Scholar
  53. 53.
    Maniongui, C., Blond, J. P., Ulmann, L., Durand, G., Poisson, J. P., & Bezard, J. (1993). Age-related-changes in delta-6 and delta-5 desaturase activities in rat-liver microsomes. Lipids, 28(4), 291–297.PubMedCrossRefGoogle Scholar
  54. 54.
    Perichon, R., & Bourre, J. M. (1995). Peroxisomal beta-oxidation activity and catalase activity during development and aging in mouse-liver. Biochimie, 77(4), 288–293.PubMedCrossRefGoogle Scholar
  55. 55.
    Appleton, K. H. R., Gunnell, D., Peters, T., Rogers, P., Kessler, D., & Ness, A. (2006). Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: Systemic review of published trials. American Journal of Clinical Nutrition, 84, 1308–1316.PubMedGoogle Scholar
  56. 56.
    Appleton, K. M., Rogers, P. J., & Ness, A. R. (2010). Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. American Journal of Clinical Nutrition, 91(3), 757–770. doi: 10.3945/ajcn.2009.28313.PubMedCrossRefGoogle Scholar
  57. 57.
    Carney, R. M., Freedland, K. E., & Steinmeyer, B. C. (2010). Omega-3 fatty acids for CHD with depression reply. Jama-Journal of the American Medical Association, 303(9), 836.CrossRefGoogle Scholar
  58. 58.
    Lesperance, F., Frasure-Smith, N., St-Andre, E., Turecki, G., Lesperance, P., & Wisniewski, S. R. (2010). The efficacy of omega-3 supplementation for major depression: A randomized controlled trial. The Journal of Clinical Psychiatry. doi: 10.4088/JCP.10m05966blu.
  59. 59.
    Kromhout, D., Giltay, E. J., & Geleijnse, J. M. (2010). n–3 Fatty acids and cardiovascular events after myocardial infarction. The New England Journal of Medicine. doi: 10.1056/NEJMoa1003603.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Wei Jiang
    • 1
    • 2
    Email author
  • Harry Oken
    • 3
  • Mona Fiuzat
    • 1
  • Linda K. Shaw
    • 4
  • Carolyn Martsberger
    • 2
  • Maragatha Kuchibhatla
    • 5
  • Rima Kaddurah-Daouk
    • 2
  • David C. Steffens
    • 2
  • Rebecca Baillie
    • 6
  • Michael Cuffe
    • 1
  • Ranga Krishnan
    • 2
    • 7
  • Christopher O’Connor
    • 1
    • 3
  • for the SADHART-CHF Investigators
  1. 1.Department of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  3. 3.Martek Biosciences CorporationColumbiaUSA
  4. 4.Duke Clinical Research InstituteDurhamUSA
  5. 5.Center for AgingDuke University Medical CenterDurhamUSA
  6. 6.Rosa & Co.San CarlosUSA
  7. 7.Duke-NUS Graduate Medical School SingaporeSingaporeSingapore

Personalised recommendations