Heart and Vessels

, Volume 30, Issue 1, pp 9–19

Association of atherosclerosis-related markers and its relationship to n-3 polyunsaturated fatty acids levels with a prevalence of coronary artery disease in an urban area in Japan

Original Article

Abstract

Higher intakes of fish and n-3 polyunsaturated fatty acids (n-3PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are associated with a reduced risk of coronary artery disease (CAD). We investigated the relationships between fish-derived n-3PUFAs and prevalence of CAD, and to assess the association of n-3PUFAs with atherosclerosis-related markers in an urban area. This study was designed as a hospital-based cross-sectional study on 649 consecutive outpatients who had undergone regular examinations between April 2009 and October 2009. After adjustments for the coronary risk factors in a multilogistic regression analysis of variables for which a significant difference was identified between the group of patients with a prevalence of CAD and the group with no prevalence of CAD, the multivariable odds ratio (95 % confidence interval) was 0.394 (0.205/0.760; P = 0.005) for the highest (92.4–373.5 μg/ml) versus lowest (6.2–40.0 μg/ml) quartile of serum EPA values and 0.433 (0.228/0.824; P = 0.011) for the highest (160.7–451.8 μg/ml) versus lowest (35.7–100.7 μg/ml) quartile of serum DHA values. Multivariate regression analyses after adjustment for risk factors showed that higher serum EPA and DHA levels were independent variables of a higher level of serum apolipoprotein A-1, a major compound of high-density lipoprotein. However, the results suggested that there might be conflicting effects of EPA and DHA in regard of the serum levels of other lipid markers. This cross-sectional study suggests that higher serum levels of n-3PUFAs were associated with a lower prevalence of CAD and an increase in serum apolipoprotein A-1 level, even in an urban area.

Keywords

Apolipoprotein A-1 Coronary artery disease High-density lipoprotein cholesterol n-3 Polyunsaturated fatty acid 

References

  1. 1.
    Kromhout D, Bosschieter EB, de Lezenne Coulander C (1985) The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 312:1205–1209PubMedCrossRefGoogle Scholar
  2. 2.
    Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S (2006) Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 113:195–202PubMedCrossRefGoogle Scholar
  3. 3.
    Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB (1997) Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med 336:1046–1053PubMedCrossRefGoogle Scholar
  4. 4.
    (1999) 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 354:447–455Google Scholar
  5. 5.
    Lavie CJ, Milani RV, Mehra MR, Ventura HO (2009) Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 54:585–594PubMedCrossRefGoogle Scholar
  6. 6.
    Mozaffarian D, Wu JH (2011) Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 58:2047–2067PubMedCrossRefGoogle Scholar
  7. 7.
    Cottin SC, Sanders TA, Hall WL (2011) The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc 70:215–231PubMedCrossRefGoogle Scholar
  8. 8.
    Wei MY, Jacobson TA (2011) Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep 13:474–483PubMedCrossRefGoogle Scholar
  9. 9.
    Farzaneh-Far R, Harris WS, Garg S, Na B, Whooley MA (2009) Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis 205:538–543PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Oda E, Hatada K, Kimura J, Aizawa Y, Thanikachalam PV, Watanabe K (2005) Relationships between serum unsaturated fatty acids and coronary risk factors: negative relations between nervonic acid and obesity-related risk factors. Int Heart J 46:975–985PubMedCrossRefGoogle Scholar
  11. 11.
    Manav M, Su J, Hughes K, Lee HP, Ong CN (2004) Omega-3 fatty acids and selenium as coronary heart disease risk modifying factors in Asian Indian and Chinese males. Nutrition 20:967–973PubMedCrossRefGoogle Scholar
  12. 12.
    Madsen T, Skou HA, Hansen VE, Fog L, Christensen JH, Toft E, Schmidt EB (2001) C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol 88:1139–1142PubMedCrossRefGoogle Scholar
  13. 13.
    Sniderman AD, Blank D, Zakarian R, Bergeron J, Frohlich J (2003) Triglycerides and small dense LDL: the twin Achilles heels of the Friedewald formula. Clin Biochem 36:499–504PubMedCrossRefGoogle Scholar
  14. 14.
    Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Japan EPA lipid intervention study (JELIS) Investigators (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369:1090–1098PubMedCrossRefGoogle Scholar
  15. 15.
    Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y, JELIS Investigators (2011) Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb 18:99–107PubMedCrossRefGoogle Scholar
  16. 16.
    Shah PK, Kaul S, Nilsson J, Cercek B (2001) Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: an idea whose time for testing is coming, part I. Circulation 104:2376–2383PubMedCrossRefGoogle Scholar
  17. 17.
    Domei T, Yokoi H, Kuramitsu S, Soga Y, Arita T, Ando K, Shirai S, Kondo K, Sakai K, Goya M, Iwabuchi M, Ueeda M, Nobuyoshi M (2012) Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ J 76:423–429PubMedCrossRefGoogle Scholar
  18. 18.
    Lee SH, Shin MJ, Kim JS, Ko YG, Kang SM, Choi D, Jang Y, Chung N, Shim WH, Cho SY, Manabe I, Ha JW (2009) Blood eicosapentaenoic acid and docosahexaenoic acid as predictors of all-cause mortality in patients with acute myocardial infarction—data from Infarction Prognosis Study (IPS) Registry. Circ J 73:2250–2257PubMedCrossRefGoogle Scholar
  19. 19.
    Hara M, Sakata Y, Nakatani D, Suna S, Usami M, Matsumoto S, Hamasaki T, Doi Y, Nishino M, Sato H, Kitamura T, Nanto S, Hori M, Komuro I, Osaka Acute Coronary Insufficiency Study (OACIS) Investigators (2012) Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction. Circ J 77:153–162PubMedCrossRefGoogle Scholar
  20. 20.
    Sugiura T, Yoshikawa D, Ishii H, Suzuki S, Kumagai S, Inoue Y, Okumura S, Isobe S, Hayashi M, Ando H, Amano T, Murohara T (2013) Relation of omega-3 fatty acid and C-reactive protein to peripheral artery disease in patients with coronary artery disease. Heart Vessels. doi:10.1007/s00380-013-0384-4 PubMedGoogle Scholar
  21. 21.
    Block RC, Harris WS, Reid KJ, Sands SA, Spertus JA (2008) EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls. Atherosclerosis 197:821–828PubMedCrossRefGoogle Scholar
  22. 22.
    Sala-Vila A, Cofán M, Mateo-Gallego R, Cenarro A, Civeira F, Ros E (2013) Eicosapentaenoic acid in serum phospholipids relates to a less atherogenic lipoprotein profile in subjects with familial hypercholesterolemia. J Nutr Biochem 24:1604–1608PubMedCrossRefGoogle Scholar
  23. 23.
    Chan DC, Watts GF, Nguyen MN, Barrett PH (2006) Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity. Am J Clin Nutr 84:37–43PubMedGoogle Scholar
  24. 24.
    Wilkinson P, Leach C, Ah-Sing EE (2005) Influence of alpha-linolenic acid and fish-oil on markers of cardiovascular risk in subjects with an atherogenic lipoprotein phenotype. Atherosclerosis 181:115–124PubMedCrossRefGoogle Scholar
  25. 25.
    Kuang YL, Paulson KE, Lichtenstein AH, Matthan NR, Lamon-Fava S (2011) Docosahexaenoic acid suppresses apolipoprotein A-I gene expression through hepatocyte nuclear factor-3β. Am J Clin Nutr 94:594–600PubMedCrossRefGoogle Scholar
  26. 26.
    Frénais R, Ouguerram K, Maugeais C, Mahot P, Charbonnel B, Magot T, Krempf M (2001) Effect of dietary omega-3 fatty acids on high-density lipoprotein apolipoprotein AI kinetics in type II diabetes mellitus. Atherosclerosis 157:131–135PubMedCrossRefGoogle Scholar
  27. 27.
    Okuda N, Ueshima H, Okayama A, Saitoh S, Nakagawa H, Rodriguez BL, Sakata K, Choudhury SR, Curb JD, Stamler J, INTERLIPID Research Group (2005) Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study. Atherosclerosis 178:371–379PubMedCrossRefGoogle Scholar
  28. 28.
    Mensink RP, Zock PL, Kester AD, Katan MB (2003) Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77:1146–1155PubMedGoogle Scholar
  29. 29.
    Franceschini G (2001) Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. Am J Cardiol 88:9N–13NPubMedCrossRefGoogle Scholar
  30. 30.
    McQueen MJ, Hawken S, Wang X, Ounpuu S, Sniderman A, Probstfield J, Steyn K, Sanderson JE, Hasani M, Volkova E, Kazmi K, Yusuf S, INTERHEART study investigators (2008) Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case–control study. Lancet 372:224–233PubMedCrossRefGoogle Scholar
  31. 31.
    Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y (2012) The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid. J Atheroscler Thromb 19:673–679PubMedCrossRefGoogle Scholar
  32. 32.
    USDA Agricultural Research Service. Nutrient data laboratory. http://www.ars.usda.gov/nutrientdata. Accessed Jan 23 2000
  33. 33.
    (2005) Standard Tables of Food Composition in Japan, 5th revised and enlarged edn. Fatty acids section. http://www.mext.go.jp/b_menu/shingi/gijyutu/gijyutu3/toushin/05031801.htm. Ministry of Education, Culture, Sports, Science and Technology, Japan
  34. 34.
    Sasaki J, Ikeda Y, Kuribayashi T, Kajiwara K, Biro S, Yamamoto K, Ageta M, Kobori S, Saikawa T, Otonari T, Kono S (2008) A 52-week, randomized, open-label, parallel-group comparison of the tolerability and effects of pitavastatin and atorvastatin on high-density lipoprotein cholesterol levels and glucose metabolism in Japanese patients with elevated levels of low-density lipoprotein cholesterol and glucose intolerance. Clin Ther 30:1089–1101PubMedCrossRefGoogle Scholar
  35. 35.
    Imaizumi S, Navab M, Morgantini C, Charles-Schoeman C, Su F, Gao F, Kwon M, Ganapathy E, Meriwether D, Farias-Eisner R, Fogelman AM, Reddy ST (2011) Dysfunctional high-density lipoprotein and the potential of apolipoprotein A-1 mimetic peptides to normalize the composition and function of lipoproteins. Circ J 75:1533–1538PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Sato A, Nozato T, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Michishita I (2013) Effects of statins on serum n-3 to n-6 polyunsaturated fatty acid ratios in patients with coronary artery disease. J Cardiovasc Pharmacol Ther 18:320–326PubMedCrossRefGoogle Scholar
  37. 37.
    Kurisu S, Ishibashi K, Kato Y, Mitsuba N, Dohi Y, Nishioka K, Kihara Y (2013) Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease. Heart Vessels 28:34–38PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  1. 1.Department of CardiologySurugadai Nihon University HospitalTokyoJapan
  2. 2.Division of Cardiology, Department of MedicineNihon University School of MedicineTokyoJapan

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