Abstract
Objectives
N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality. Administration of N-3 fatty acids to patients treated with statins may potentiate the treatment effects. We examined the operating mechanisms underlying such a combination.
Methods
Thirty-two hypercholesterolemic patients aged 30–70 years with hypercholesterolemia controlled by statins, received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks. Scheduled clinical visits included physical examination, 24-h blood pressure measurement, endothelial function evaluated by pulse wave analysis, analyses for platelet function, inflammation markers [interleukin (IL)-6, plasminogen activator inhibitor-1 (PAI-1)] and oxidative stress parameters (STAT-8-Isoprostane) were undertaken at baseline, after placebo treatment, and after 6 and 20 weeks of N-3 fatty acid intake.
Results
Platelets functions were significantly inhibited, whereas endothelial function parameters were unaltered. IL-6 significantly decreased whereas PAI-1and STAT-8-Isoprostane levels remained unaffected. Daytime blood pressure significantly decreased; however, nighttime pressure and heart rate remained unchanged. No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids.
Conclusions
In hypercholesterolemic patients, combination of statins and N-3 fatty acid inhibits platelet aggregation, alters inflammatory status, and positively affects daytime blood pressure. Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population.
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References
Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, GISSI-Prevenzione Investigators et al (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105(16):1897–1903
Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P et al (1997) Fish consumption and the 30-year risk of fatal myocardial infarction. NEJM 336:1946–1053
De Ceterina R, Madonna R, Zucchi R, Tersesa M (2003) Antiarrhythmic effect of omega-3 fatty acids: from epidemiology to bedside. Am Heart J 146(3):420–430
Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ et al AHA dietary guidelines: revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation 102:2284–2299
London B, Albert C, Anderson ME, Giles WR, Van Wagoner DR, Balk E et al (2007) Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the national heart, lung, and blood institute and office of dietary supplements omega-3 fatty acids and their role in cardiac arrhythmogenesis. Circulation 116:e320–e335
Woodman RJ, Mori TA, Burke V, Puddey IB, Barden A, Watts GF et al (2003) Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrilolytic and vascular function in Type 2 diabetic patients. Atherosclerosis 166:85–93
Fahs C, Yan H, Ranadive S, Rossow L, Agiovlasitis S, Ket W et al (2010) The effect of acute fish-oil supplementation on endothelial function and arterial stiffness following a high-fat meal. Appl Physiol Nutr Metab 35(3):294–302
McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR et al (1993) Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36(1):33–38
Ferguson JF, Phillips CM, McMonagle J, Pérez-Martínez P, Shaw DI, Lovegrove JA et al (2010) NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids. Atherosclerosis. Mar 27
Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 15;108(2):155–160
Sala-Vila A, Cofán M, Pérez-Heras A, Núñez I, Gilabert R, Junyent M et al (2010) Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia. Am J Clin Nutr. May 12
Cholesterol Treatment Trialists’ (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366:1267–1278
Davignon J (2004) Beneficial cardiovascular pleiotropic effects of statins. Circulation 109(suppl):III-39–III-43
Nissen S (2004) High-dose statins in acute coronary syndromes: not just lipid levels. JAMA 292:1365–1367
Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y et al (2008) JELIS Investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 200(1):135–140
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
U.S. Food and Drug Administration Centre for Drug Evaluation and Research (1992) Approved Drug Products With Therapeutic Equivalence Evaluation (Orange Book), 12th edn. U.S. Department of Health and Human Services, Washington, DC
Tanaka K, Ishikawa Y, Yokoyama M, Origasa H, Matsuzaki M, Saito Y, JELIS Investigators, Japan et al (2008) Japan. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 39(7):2052–2058
Carroll D, Roth M (2002) Evidence for the cardioprotective effects of omega-3 fatty acids. Ann Pharmacother 36:1950–1956
Lichtenstein A (2005) Remarks on clinical data concerning dietary supplements that affect antithrombotic therapy. Thromb Res 117:71–73
Kromhout D, Giltay E, Geleijnse J, Alpha Omega Trial Group (2010) N–3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 363:2015–2026
Liao JK (2005) Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol. Am J Cardiol 96(5A):24F–33F
Mangalmurti SS, Davidson MH The Incremental Value of Lipids and Inflammatory Biomarkers in Determining Residual Cardiovascular Risk. Curr Atheroscler Rep. 2011 Jul 20. [Epub ahead of print]
Goodnight S, Harris W, Connor W, Illingworth D (1981) The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study blood Nov;58(5):880–885
Santos M, Fuset M, Ruano M, Moscardó A, Valles (2009) Effect of atorvastatin on platelet thromboxane A(2) synthesis in aspirin-treated patients with acute myocardial infarction. JAm J Cardiol 15:104(12):1618–1623
Morris MC, Sacks F, Rosner B (1993) Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 88:523–533
Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ (2002) Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 20(8):1493–1499
Sommerfield T, Price J, Hiatt WR. Omega-3 fatty acids for intermittent claudication. Cochrane database of systematic reviews
Jones D, Hall J (2004) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and evidence from new hypertension trials. Hypertension 43(1):1–3
Acknowledgement
We thank Solgar Vitamin and Herb Company, for their generous donation of the Omega-3 capsules used in the study. We also thank Mr. Roy Sagi and Ms. Ora Sagi for their invaluable assistance with patient management during the study period.
Conflict of interest statement
None of the authors had financial or personal relationships with other people, or organizations, that could inappropriately influence (bias) their work.
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Doenyas-Barak, K., Berman, S., Abu-Hamad, R. et al. N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients’ daytime blood pressure, and improves inflammatory status. Eur J Clin Pharmacol 68, 1139–1146 (2012). https://doi.org/10.1007/s00228-012-1235-4
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DOI: https://doi.org/10.1007/s00228-012-1235-4