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Effect of purified eicosapentaenoic acid on red cell distribution width in patients with ischemic heart disease

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Abstract

A recent study showed eicosapentaenoic acid (EPA) is a promising treatment for prevention of coronary events in hypercholesterolemic patients. Meanwhile, a high red blood cell distribution width (RDW) is a known risk factor for cardiovascular events. However, few studies have addressed the association between EPA levels and RDW. We examined whether EPA administration reduced the levels of RDW in patients with ischemic heart disease (IHD). We retrospectively analyzed the data of 66 EPA-treated IHD patients, and these EPA-treated patients were compared with control IHD patients. The median follow-up period was 189 days in EPA-treated patients. All patients were not associated with anemia. In the follow-up period, the ratio of EPA levels to arachidonic acid levels (EPA/AA) was significantly increased. A significant decrease was observed in RDW at follow-up [ΔRDW (%); EPA vs. control = −0.34 ± 0.84 (SD) vs. 0.08 ± 0.86, P < 0.01]. These RDW changes were more marked in diabetic patients with high serum levels of high-sensitive C-reactive protein (hs-CRP) [ΔRDW (%); EPA vs. control = −0.53 ± 0.69 vs. 0.56 ± 0.85, P < 0.01]. There was no correlation between the amount of change in EPA/AA and RDW (R = 0.037, P = 0.32), but a significant negative correlation was observed in diabetic patients with high hs-CRP levels (N = 14, R = −0.506, P = 0.046). In conclusion, EPA has the potential to reduce RDW in IHD patients. This effect was intensified especially among diabetic patients with high hs-CRP levels. IHD patients with high RDW levels may be suitable for treatment with purified EPA.

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Abbreviations

EPA:

Eicosapentaenoic acid

AA:

Arachidonic acid

DHA:

Docosahexaenoic acid

PUFAs:

n-3 Polyunsaturated fatty acids

RDW:

Red blood cell distribution width

IHD:

Ischemic heart disease

hs-CRP:

High-sensitive C-reactive protein

RBC:

Red blood cell

PCI:

Percutaneous coronary intervention

CABG:

Coronary artery bypass grafting

OMI:

Old myocardial infarction

DM:

Diabetes mellitus

HbA1c:

Hemoglobin A1c

TGL:

Triglycerides

Cr:

Serum creatinine

eGFR:

Estimated glomerular filtration rate

EPA/AA:

Ratio of EPA to AA

ACS:

Acute coronary syndrome

References

  1. Albert CM, Hennekens CH, O’Donnell CJ (1998) Fish consumption and risk of sudden cardiac death. JAMA 279:23–28

    Article  CAS  PubMed  Google Scholar 

  2. Siscovick DS, Raghunathan TE, King I, Weinmann S, Wicklund KG, Albright J, Bovbjerg V, Arbogast P, Smith H, Kushi LH, Cobb LA, Copass MK, Psaty BM, Lemaitre R, Retzlaff B, Childs M, Knopp RH (1995) Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 274:1363–1367

    Article  CAS  PubMed  Google Scholar 

  3. 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 369:1090–1098

    Article  CAS  PubMed  Google Scholar 

  4. Zhang M, Hagiwara S, Matsumoto M, Gu L, Tanimoto M, Nakamura S, Kaneko S, Gohda T, Qian J, Horikoshi S, Tomino Y (2006) Effects of eicosapentaenoic acid on the early stage of type 2 diabetic nephropathy in KKA(y)/Ta mice: involvement of anti-inflammation and antioxidative stress. Metabolism 55:1590–1598

    Article  CAS  PubMed  Google Scholar 

  5. von Schacky C, Weber PC (1985) Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J Clin Invest 76:2446–2450

    Article  Google Scholar 

  6. Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM (2009) Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med 169:515–523

    Article  PubMed Central  PubMed  Google Scholar 

  7. Patel KV, Mohanty JG, Kanapuru B, Hesdorffer C, Ershler WB, Rifkind JM (2013) Association of the red cell distribution width with red blood cell deformability. Adv Exp Med Biol 765:211–216

    Article  CAS  PubMed  Google Scholar 

  8. International Expert Committee (2009) International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32:1327–1334

    Article  Google Scholar 

  9. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Rydén L, Sirenko Y, Stanton A, Struijker-Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA (2013) 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 34(28):2159–2219

    Article  PubMed  Google Scholar 

  10. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E (2009) 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult––2009 recommendations. Can J Cardiol 25:567–579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992

    Article  CAS  PubMed  Google Scholar 

  12. 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(2):99–107

    Article  CAS  PubMed  Google Scholar 

  13. Arima H, Kubo M, Yonemoto K, Ninomiya T, Tanizaki Y, Hata J, Matsumura K, Iida M, Kiyohara Y (2008) High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study. Arterioscler Thromb Vasc Biol 28:1385–1391

    Article  CAS  PubMed  Google Scholar 

  14. Ridker PM (2001) High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 103(13):1813–1818

    Article  CAS  PubMed  Google Scholar 

  15. Kondo T, Ogawa K, Satake T, Kitazawa M, Taki K, Sugiyama S, Ozawa T (1986) Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor. Clin Cardiol 9:413–416

    Article  CAS  PubMed  Google Scholar 

  16. Ueeda M, Doumei T, Takaya Y, Ohnishi N, Takaishi A, Hirohata S, Miyoshi T, Shinohata R, Usui S, Kusachi S (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(2):145–152

    Article  PubMed  Google Scholar 

  17. Hayakawa S, Yoshikawa D, Ishii H, Tanaka M, Kumagai S, Matsumoto M, Hayashi M, Sugiura T, Hayashi K, Ando H, Amano T, Murohara T (2012) Association of plasma omega-3 to omega-6 polyunsaturated fatty acid ratio with complexity of coronary artery lesion. Intern Med 51:1009–1014

    Article  CAS  PubMed  Google Scholar 

  18. Hasegawa T, Otsuka K, Iguchi T, Matsumoto K, Ehara S, Nakata S, Nishimura S, Kataoka T, Shimada K, Yoshiyama M (2013) Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study. Heart Vessels. doi:10.1007/s00380-013-0404-4

    Google Scholar 

  19. Grundy SM (2001) Dietary fat: at the heart of the matter. Science 293(5531):801–804

    Article  CAS  PubMed  Google Scholar 

  20. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC (2010) 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 212:252–259

    Article  CAS  PubMed  Google Scholar 

  21. Koma Y, Onishi A, Matsuoka H, Oda N, Yokota N, Matsumoto Y, Koyama M, Okada N, Nakashima N, Masuya D, Yoshimatsu H, Suzuki Y (2013) Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer. PLoS One 8:e80240

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Dugdale AE (2006) Predicting iron and folate deficiency anaemias from standard blood testing: the mechanism and implications for clinical medicine and public health in developing countries. Theor Biol Med Model 3:34

    Article  PubMed Central  PubMed  Google Scholar 

  23. James SK, Lindahl B, Timmer JR, Ottervanger JP, Siegbahn A, Stridsberg M, Armstrong P, Califf R, Wallentin L, Simoons ML (2006) Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (a GUSTO IV substudy). Am J Cardiol 97:167–172

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research(C) 22590822 to Y.H. by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masao Takahashi, Masahiro Myojo, Aya Watanabe, Arihiro Kiyosue, Koichi Kimura, Jiro Ando & Issei Komuro

  2. Department of Cardiovascular Medicine, Tokyo Teishin Hospital, Tokyo, Japan

    Yasunobu Hirata

Authors
  1. Masao Takahashi
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  2. Masahiro Myojo
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  3. Aya Watanabe
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Correspondence to Masao Takahashi.

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Takahashi, M., Myojo, M., Watanabe, A. et al. Effect of purified eicosapentaenoic acid on red cell distribution width in patients with ischemic heart disease. Heart Vessels 30, 587–594 (2015). https://doi.org/10.1007/s00380-014-0526-3

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  • DOI: https://doi.org/10.1007/s00380-014-0526-3

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