Heart and Vessels

, Volume 28, Issue 1, pp 34–38

Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease

  • Satoshi Kurisu
  • Ken Ishibashi
  • Yasuko Kato
  • Naoya Mitsuba
  • Yoshihiro Dohi
  • Kenji Nishioka
  • Yasuki Kihara
Original Article

Abstract

Residual risk of cardiovascular events after treatment with stain might be explained in part because patients have low levels of n−3 polyunsaturated fatty acids (PUFA). We examined how lipid-lowering therapy with strong statin affected serum PUFA levels in patients with coronary artery disease. The study population consisted of 46 patients with coronary artery disease whose low-density lipoprotein (LDL) cholesterol was more than 100 mg/dl. Lipid-lowering therapy was performed with a strong statin including atorvastatin (n = 22), rosuvastatin (n = 9) or pitavastatin (n = 15). Serum PUFA levels were determined by gas chromatography. The treatment with strong statin decreased the sum of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) levels (195 ± 41 to 184 ± 44 μg/ml, P < 0.05) as well as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (233 ± 71 to 200 ± 72 μg/ml, P < 0.001). These effects of strong statin resulted in a significant decrease in ratio of the sum of EPA and DHA levels to the sum of DGLA and AA levels (1.20 ± 0.27 to 1.10 ± 0.35, P < 0.05). The percent decrease in the LDL cholesterol level correlated significantly with that in the sum of EPA and DHA levels (r = 0.38, P < 0.01). In conclusion, our results showed that lipid-lowering therapy with strong statin mainly reduced n−3 PUFAs in proportion to the decrease in the LDL cholesterol level in patients with coronary artery disease.

Keywords

Polyunsaturated fatty acid Statin Coronary artery disease Residual risk 

References

  1. 1.
    Scandinavian Simvastatin Survival Study Group (1994) Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389Google Scholar
  2. 2.
    Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E (1996) The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 335:1001–1009PubMedCrossRefGoogle Scholar
  3. 3.
    The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 339:1349–1357Google Scholar
  4. 4.
    Fujita M, Yamazaki T, Hayashi D, Kohro T, Okada Y, Nagai R, JCAD Study Investigators et al (2008) Pleiotropic effects of statins on cardiovascular events in the Japanese Coronary Artery Disease study. Int J Cardiol 129:294–296PubMedCrossRefGoogle Scholar
  5. 5.
    Tavridou A, Efthimiadis A, Efthimiadis I, Manolopoulos VG (2010) Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia. Heart Vessels 25:288–293PubMedCrossRefGoogle Scholar
  6. 6.
    Ridker PM, Genest J, Boekholdt SM, Libby P, Gotto AM, Nordestgaard BG, Mora S, MacFadyen JG, Glynn RJ, Kastelein JJ, JUPITER Trial Study Group et al (2010) HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet 376:333–339PubMedCrossRefGoogle Scholar
  7. 7.
    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 29:673–685PubMedCrossRefGoogle Scholar
  8. 8.
    Harris WS, Poston WC, Haddock CK (2007) Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 193:1–10PubMedCrossRefGoogle Scholar
  9. 9.
    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
  10. 10.
    Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, Ma J (2002) Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 346:1113–1118PubMedCrossRefGoogle Scholar
  11. 11.
    Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE (2002) Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA 287:1815–1821PubMedCrossRefGoogle Scholar
  12. 12.
    Ueeda M, Doumei T, Takaya Y, Ohnishi N, Takaishi A, Hirohata S, Miyoshi T, shinohata R, Usui S, Kusachi S et al (2011) Association of serum levels of arachidonic acid and eicosapentaenoic acid with prevalence of major adverse cardiac events after acute myocardial infarction. Heart Vessels 26:145–152PubMedCrossRefGoogle Scholar
  13. 13.
    Rupp H, Rupp TP, Alter P, Maisch B (2010) Inverse shift in serum polyunsaturated and monounsaturated fatty acids is associated with adverse dilatation of the heart. Heart 96:595–598PubMedCrossRefGoogle Scholar
  14. 14.
    Yli-Jama P, Meyer HF, Ringstad J, Pedersen JI (2002) Serum fatty acid pattern and risk of myocardial infarction: a case–control study. J Intern Med 251:19–28PubMedCrossRefGoogle Scholar
  15. 15.
    Kaluzny MA, Duncan LA, Merritt MV, Epps DE (1985) Rapid separation of lipid classes in high yield and purity using bonded phase columns. J Lipid Res 26:135–140PubMedGoogle Scholar
  16. 16.
    Folch J, Lees M, Sloane M, Stanley G (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509PubMedGoogle Scholar
  17. 17.
    Hoshi M, Williams M, Kishimoto Y (1973) Esterification of fatty acids at room temperature by chloroform-methanolic HCL-cupric acetate. J Lipid Res 14:599–601PubMedGoogle Scholar
  18. 18.
    Shishehbor MH, Zhang R, Medina H, Brennan ML, Brennan DM, Ellis SG, Topol EJ, Hazen SL (2006) Systemic elevations of free radial oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease. Free Radic Biol Med 41:1678–1683PubMedCrossRefGoogle Scholar
  19. 19.
    Tretjakovs P, Kalnins U, Dabina I, Erglis A, Dinne I, Jurka A, Latkovskis G, Zvaiqzne A, Piraqs V (2003) Nitric oxide production and arachidonic acid metabolism in platelet membranes of coronary heart disease patients with and without diabetes. Med Princ Pract 12:10–16PubMedCrossRefGoogle Scholar
  20. 20.
    Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M et al (2004) Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid and atherosclerosis. N Engl J Med 350:29–37PubMedCrossRefGoogle Scholar
  21. 21.
    Terano T, Salmon JA, Moncada S (1984) Effect of orally administered eicosapentaenoic acid (EPA) on the formation of leukotriene B4 and leukotriene B5 by rat leukocytes. Biochem Pharmacol 33:3071–3076PubMedCrossRefGoogle Scholar
  22. 22.
    Wallace JM, Turley E, Gilmore WS, Strain JJ (1995) Dietary fish oil supplementation alters leukocyte function and cytokine production in healthy women. Arterioscler Thromb Vasc Biol 15:185–189PubMedCrossRefGoogle Scholar
  23. 23.
    Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto miocardico (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354:447–455Google Scholar
  24. 24.
    Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y, JELIS Investigators (2009) Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease: secondary prevention analysis from JELIS. Circ J 73:1283–1290PubMedCrossRefGoogle Scholar
  25. 25.
    Nakamura N, Hamazaki T, Ohta M, Okuda K, Urakaze M, Sawazaki S, Yamazaki K, Satoh A, Temaru R, Ishikura Y, Takata M, Kishida M, Kobayashi M (1999) Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 29:22–25PubMedCrossRefGoogle Scholar
  26. 26.
    Jula A, Marniemi J, Ronnemaa T, Virtanen A, Huupponen R (2005) Effects of diet and simvastatin on fatty acid composition in hypercholesterolemic men. Arterioscler Thromb Vasc Biol 25:1952–1959PubMedCrossRefGoogle Scholar
  27. 27.
    Das UN (2011) Beneficial actions of statins in the reduction of atrial fibrillation and stabilization and regression of coronary plaques: but how and why? Circ J 75:224–225PubMedCrossRefGoogle Scholar
  28. 28.
    Garg ML, Snoswell AM, Sabine JR (1986) Influence of dietary cholesterol on desaturase enzymes of rat liver microsomes. Prog Lipid Res 25:639–644PubMedCrossRefGoogle Scholar
  29. 29.
    Leikin AI, Brenner RR (1988) In vivo cholesterol removal from liver microsomes induces changes in fatty acid desaturase activities. Biochim Biophys Acta 963:311–319PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Satoshi Kurisu
    • 1
  • Ken Ishibashi
    • 1
  • Yasuko Kato
    • 1
  • Naoya Mitsuba
    • 1
  • Yoshihiro Dohi
    • 1
  • Kenji Nishioka
    • 1
  • Yasuki Kihara
    • 1
  1. 1.Department of Cardiovascular MedicineHiroshima University Graduate School of Biomedical SciencesHiroshimaJapan

Personalised recommendations