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Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability

Abstract

Background:

This study was designed to evaluate the effects of omega-3 fatty acids supplements and simvastatin on lipoproteins and heart rate variability (HRV), a surrogate parameter of cardiac autonomic function, in patients with mixed dyslipidemia.

Methods:

This study was a prospective, randomized, open-label study. Among the 171 patients screened, 62 who met the inclusion criteria after 6 weeks on a strict diet therapy were randomized into two treatment groups. The inclusion criteria were mixed dyslipidemia with a high triglyceride level (200–499 mg per 100 ml) and a total cholesterol level >200 mg per 100 ml. After a run-in period of 6 weeks, the patients were randomized into two groups and given a combination treatment with 4 g of omega-3 fatty acids (four 1 g Omacor (eicosapentaenoic acid, 465 mg; docosahexaenoic acid, 375 mg; other omega-3 fatty acids, 60 mg; others 100 mg, Gun-il Pharmacy, Seoul, Korea)) and 20 mg of simvastatin daily or a monotherapy of 20 mg simvastatin for 6 weeks. In the combination therapy group, seven patients dropped out, and in the simvastatin alone therapy group, five patients dropped out during the study period.

Results:

After 6 weeks of drug treatment, triglyceride levels decreased by 41.0% in the combination treatment group and 13.9% in the simvastatin monotherapy group (from 309.2±95 mg per 100 ml to 177.7±66 versus 294.6±78 mg per 100 ml to 238.3±84 mg per 100 ml, respectively, P=0.0007). No significant changes in the HRV parameters were observed in either group.

Conclusion:

The combination of omega-3 fatty acids plus simvastatin, which achieved a significantly greater reduction of triglycerides without adverse reactions, should be considered as an optimal treatment option for patients with mixed dyslipidemia.

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References

  • Calabresi L, Donati D, Pazzucconi F, Sirtori CR, Franceschini G (2000). Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis 148, 387–396.

    Article  CAS  Google Scholar 

  • Calabresi L, Villa B, Canavesi M, Sirtori CR, James RW, Bernini F et al. (2004). An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism 53, 153–158.

    Article  CAS  Google Scholar 

  • Chen GY, Hsiao TJ, Lo HM, Kuo CD (2008). Abdominal obesity is associated with autonomic nervous derangement in healthy Asian obese subjects. Clin Nutr 27, 212–217.

    Article  Google Scholar 

  • Christensen JH, Korup E, Aarøe J, Toft E, Møller J, Rasmussen K et al. (1997). Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction. Am J Cardiol 79, 1670–1673.

    Article  CAS  Google Scholar 

  • Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitx RA, et al., for the COMBOS Investigators (2007). Efficacy and Tolerability of Adding Prescription Omega-3 Fatty Acids 4 g/d to Simvastatin 40 mg/d in Hypertriglyceridemic Patients: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Study. Clin Ther 29, 1354–1367.

    Article  CAS  Google Scholar 

  • Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA et al. (2001). An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart 85, 544–548.

    Article  CAS  Google Scholar 

  • Geelen A, Zock PL, Swenne CA, Brouwer IA, Schouten EG, Katan MB (2003). Effect of n-3 fatty acids on heart rate variability and baroreflex sensitivity in middle-aged subjects. Am Heart J 146, E4.

    Article  Google Scholar 

  • Gentlesk PJ, Wiley T, Taylor AJ (2005). A prospective evaluation of the effect of simvastatin on heart rate variability in non-ischemic cardiomyopathy. Am Heart J 150, 478–483.

    Article  CAS  Google Scholar 

  • Goyens PLL, Mensink RP (2006). Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects. Eur J Clin Nutr 60, 978–984.

    Article  CAS  Google Scholar 

  • Harris WS (1997). n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 65 (suppl), 1645S–1654S.

    Article  CAS  Google Scholar 

  • Kabir M, Skurnik G, Naour A, Pechtner V, Meugnier E, Rome S et al. (2007). Treatment for 2 mo with n-3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 86, 1670–1679.

    Article  CAS  Google Scholar 

  • Kleiger RE, Miller JP, Bigger JT, Moss AJ (1987). Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59, 256–262.

    Article  CAS  Google Scholar 

  • La Rovere MT, Bigger JT, Marcus FI, Mortara A, Schwartz PJ (1998). Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351, 478–484.

    Article  CAS  Google Scholar 

  • Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS (2003). n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr 77, 319–325.

    Article  CAS  Google Scholar 

  • Madsen T, Skou HA, Hansen VE, Fog L, Christensen JH, Toft E et al. (2001). C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol 88, 1139–1142.

    Article  CAS  Google Scholar 

  • Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR (2008). Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol 102, 429–433.

    Article  CAS  Google Scholar 

  • Meredith KG, Horne BD, Pearson RR, Maycock CA, Lappe DL, Anderson JL et al. (2007). Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C-reactive protein and lipoproteins in patients with angiographic evidence of coronary arterial narrowing. Am J Cardiol 99, 149–153.

    Article  CAS  Google Scholar 

  • Mozaffarian D, Stein PK, Prineas RJ, Siscovick DS (2008). Dietary fish and omega-3 fatty acid consumption and heart rate variability in US adults. Circulation 117, 1130–1137.

    Article  CAS  Google Scholar 

  • Pehlivanidis AN, Athyros VG, Demitriadis DS, Papageorgiou AA, Bouloukos VJ, Kontopoulos AG (2001). Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease. Atherosclerosis 157, 463–469.

    Article  CAS  Google Scholar 

  • Perkiömäki JS, Huikuri HV, Koistinen JM, Mäkikallio T, Castellanos A, Myerburg RJ (1997). Heart rate variability and dispersion of QT interval in patients with vulnerability to ventricular tachycardia and ventricular fibrillation after previous myocardial infarction. J Am Coll Cardiol 30, 1331–1338.

    Article  Google Scholar 

  • Plenge JK, Hernandez TL, Weil KM, Poirier P, Grunwald GK, Marcovina SM et al. (2002). Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 106, 1447–1452.

    Article  CAS  Google Scholar 

  • Riahi S, Schmidt EB, Amanavicius N, Karmisholt J, Jensen HS, Christoffersen RP et al. (2006). The effect of atorvastatin on heart rate variability and lipoproteins in patients treated with coronary bypass surgery. Int J Cardiol 111, 436–441.

    Article  Google Scholar 

  • Szabo BM, Van Veldhuisen DJ, Brouwer J, Haaksma J, Lie KI (1995). Relation between severity of disease and impairment of heart rate variability parameters in patients with chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 76, 713–716.

    Article  CAS  Google Scholar 

  • Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP et al. (2003). Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477–485.

    Article  CAS  Google Scholar 

  • Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al., 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  Google Scholar 

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Acknowledgements

This work was supported by the Innovative Research Institute for Cell Therapy (IRICT) and the Clinical Research Center for Ischemic Heart Disease (0412-CR02-0704-0001). Dr Hyo-Soo Kim is a professor of Molecular Medicine & Biopharmaceutical Sciences, Seoul National University sponsored by World Class University Program from the Ministry of Education, Science, and Technology, Korea.

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Correspondence to Hyo-Soo Kim.

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Kim, SH., Kim, MK., Lee, HY. et al. Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability. Eur J Clin Nutr 65, 110–116 (2011). https://doi.org/10.1038/ejcn.2010.195

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