Role of Polyunsaturated Fatty Acids in Cardiovascular Diseases

  • Mohammad Asif Mail Department of Pharmacy, GRD (PG) IMT, Dehradun, India.
Cardiovascular Diseases, Fish Oils, Omega-3 Fatty Acids


Polyunsaturated fatty acids (PUFAs) particularly ω-3 PUFAs showed great assure in prevention of cardiovascular diseases (CVD). The evidence for CV benefits of PUFA comes from eicosapentaenoic acid (EPA) with or without docosahexaenoic acid (DHA) in primary prevention, after myocardial infarction (MI), with heart failure (HF). The epidemiologic studies and trials showing the benefits of PUFA, specifically EPA and DHA, in CV prevention and provide potential mechanisms. The target EPA and DHA consumption should be at least 500 mg/day for individuals without basic evident CV disease and at least 800 to 1,000 mg/day for individuals with known coronary heart disease (CHD) and heart failure (HF) and optimal dosing and relative ratio of DHA and EPA ω-3 PUFA that provides maximum cardio-protection at risk of CVD as well in treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.


Tayyebi-Khosroshahi H, Houshyar J, Tabrizi A, Vatankhah A, Zonouz NR, Dehghan-Hesari R. Effect of Omega-3 Fatty Acid on Oxidative Stress in Patients on Hemodialysis. Iran Jf Kidney Dis 2010; 4(4): 322-326.

Harris WS, Jacobson TA. Omega-3 fatty acids. In: Ballantyne CM, editor. Clinical Lipidology: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: Saunders, an imprint of Elsevier Inc., 2009:326 –38.

Anand RG, Alkadri M, Lavie CJ, Milani RV. The role of fish oil in arrhythmia prevention. J Cardiopulm Rehabil 2008; 28:92– 8.

Harris WS. The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr 2008; 87:1997S–2002S.

Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007; 99:44C–6C.

Harris WS. Omega-3 fatty acids and cardiovascular disease a case for omega-3 index as a new risk factor. Pharmacol Res 2007; 55:217–23.

Aro A, Jauhiainen M, Partanen R, Salminen I, Mutanen M. Stearic acid, trans fatty acids, and dairy fat: effects on serum and lipoprotein lipids, apolipoproteins, lipoprotein(a), and lipid transfer proteins in healthy subjects. Am J Clin Nutr 1997; 65: 1419-1426.

Almendingen K, Jordal O, Kierulf P, Sanstad B, Pedersen J I. Effects of partially hydrogenated fish oil, partially hydrogenated soybean oil, and butter on serum lipoproteins and Lp(a) in men. J Lipid Res 1995; 36: 1370- 1384.

Breslow JL. ω- fatty acids and cardiovascular disease. Am J Clin Nutr 2006; 83: 1477S–1482S.

Danthi SJ, Enyeart JA, Enyeart JJ. Modulation of native T-type calcium channels by omega-3 fatty acids. Biochem Biophys Res Commun 2005; 327: 485–493.

Xiao YF, Sigg DC, Leaf A. The antiarrhythmic effect of ω- polyunsaturated fatty acids: modulation of cardiac ion channels as a potential mechanism. J Membr Biol 2005; 206: 141–154.

Thies F, Garry JM, Yaqoob P, et al. Association of ω- polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomized controlled trial. Lancet 2003; 361: 477–485.

Yin K, Chu ZM, Beilin LJ. Effect of fish oil feeding on blood pressure and vascular reactivity in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 1990; 17: 235–239.

Nyby MD, Hori MT, Ormsby B, Gabrielian A, Tuck ML. Eicosapentaenoic acid inhibits Ca2+ mobilization and PKC activity in vascular smooth muscle cells. Am J Hypertens 2003; 16: 708-714.

Theuer J, Shagdarsuren E, Muller DN, et al. Inducible NOS inhibition, eicosapentaenoic acid supplementation, and angiotensin II-induced renal damage. Kidney Int 2005; 67: 248–258.

Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 2008; 83:324 –32.

Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998; 279:23– 8.

Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 370:220.

Kris-Etherton PM, Harris WS, Appel LJ. American Heart Association Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2003; 107: 512.

Mata P, Garrido JA, Ordovas JM, et al. Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women. Am J Clin Nutr 1992; 56: 77-83.

William H. Omega-3 fatty acids: the “Japanese” factor? J Am Coll Cardiol 2008; 52:425–7.

Harris WS, Poston WC, Haddock CK. Tissue ω- and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 2007;193: 1–10.

Macchia A, Levantesi G, Franzosi MG, et al. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with ω- polyunsaturated fatty acids. Eur J Heart Fail 2005; 7: 904 –9.

Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by ω- 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 2002; 105: 1897–1903.

Bays H, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther 2008; 6:391– 409.

Fischer R, Dechend R, Qadri F, et al. Dietary ω- polyunsaturated fatty acids and direct renin inhibition improve electrical remodeling in a model of high human rennin hypertension. Hypertension 2008; 51: 540-546.

Fonarow GC. Statins and ω- fatty acid supplementation in heart failure. Lancet 2008; 372: 1195- 6.

Burr ML, Ashfield-Watt PA, Dunstan FD, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr 2003; 57: 193–200.

von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids.Cardiovasc Res 2007; 73: 310 –5.

Nilsen DW, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L. Effects of a high-dose concentrate of ω- fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am J Clin Nutr 2001; 74: 50–6.

Senges S. OMEGA Study Group. Randomized trial of omega-3 fatty acids on top of modern therapy after acute myocardial infarction: the OMEGA trial. Oral presentation at: Annual Scientific Sessions of the American College of Cardiology; March 2009; Orlando, FL.

Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab 2007; 32: 619 –34.

Wang C, Harris WS, Chung M, et al. ω- fatty acid from fish or fish-oil supplements, but not (alpha)-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006; 84: 5–17.

Campos H, Baylin A, Wilett WC. α-linolenic acid and risk of nonfatal acute myocardial infarction. Circulation 2008; 118:339–45.

Seikikawa A, Ueshima H, Kadowaki T, et al. Less subclinical atherosclerosis in Japanese men in Japan than in white men in the United States in the post– World War II birth cohort. Am J Epidemiol 2007; 165:617–24.

Seikikawa A, Curb JD, Ueshima H. Marine-derived ω- fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a crosssectional study. J Am Coll Cardiol 2008;52:417–24.

Reiffel JA, McDonald A. Antiarrhythmic effects of omega-3 fatty acids. Am J Cardiol 2006; 98:501– 601.

Christensen JH, Gustenhoff P, Korup E, et al. Effect of fish oil on heart rate viability in survivors of myocardial infarction: a double blind randomized controlled trial. Br Med J 1996; 312: 677– 8.

O’Keefe JH Jr., Abuissa H, Sastre A, Steinhaus DM, Harris WS. Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate viability in men with healed myocardial infarctions and depressed ejection fractions. Am J Cardiol 2006; 97:1127–30.

Geelen A, Brouwer IA, Schouten EG, Maan AC, Katan MB, Zock PI. Effects of ω- fatty acids from fish on premature ventricular complexes and heart rate in humans. Am J Clin Nutr 2005; 81:416 –20.

Mozaffarian D, Prineas RJ, Stein PK, Siscovick DS. Dietary fish and ω- fatty acid intake and cardiac electrocardiographic parameters in humans. J Am Coll Cardiol 2006; 48: 478–484.

Brouwer IA, Heeringa J, Geleijnse JM, Zock PL, Witteman JC. Intake of very long-chain ω- fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study. Am Heart J 2006; 151: 857–62.

Brouwer IA, Zock PL, Camm AJ, et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006; 295: 2613–9.

Calo L, Bianconi L, Colivicchi F, et al. Ω- Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol 2005; 45: 1723–1728.

Crystal E, Garfinkle MS, Conolly SS, Ginger TT, Sleik K, Yusuf SS. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev 2004; 4: CD003611.

Mozaffarian D, Bryson CL, Lemaitre RN, Burke GL, Siscovick DS. Fish intake and risk of incident heart failure. J Am Coll Cardiol 2005; 45: 2015– 21.

Yamagishi K, Nettleton JA, Folsom AR. Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) study. Am Heart J 2008; 156: 965–74.

Kliewer SA, Sundseth SS, Jones SA, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferators-activated receptors alpha and gamma. Proc Natl Acad Sci USA 1997; 94: 4318 –23.

Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferators-activated receptors. Mol Cell 1999; 3:397-403.

Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005;85: 1093–129.

Duda MK, O’Shea KM, Lei B, et al. Dietary supplementation with omega-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload. Cardiovasc Res 2007;76:303–10.

Neschen S, Morino K. Rossbacker JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptorgamma-dependent mechanism in mice. Diabetes 2006; 55:924–8.

Itoh M, Suganami T, Satoh N, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 2007; 27:1918–25.

Shibata R, Sato K, Pimentel DR, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through. Nat Med 2005;11: 1096– 103.

Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007;380:24-30.

Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce antiinflammatory effects and improved body weight in severe heart failure. J Heart Lung Transplant 2006;25:834–8.

Bays H. Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J Cardiol 2006; 98:71i– 6i.

Bays H. Rationale for prescription omega-3-acid ethylester therapy for hypertriglyceridemia: a primer for clinicians. Drugs Today (Barc) 2008; 44:205– 46.

Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409 –35.

Huang B, Wu P, Bowker-Kinley MM, Harris RA. Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferatoractivated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 2002; 51:276– 83.

Harris WS, Ginsberg HN, Arunakul N, et al. Safety and efficacy of Omacor in severe hyper triglyceridemia. J Cardiovasc Risk 1997; 4: 385–91.

Harris WS. Ω- fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997; 65 Suppl:1645S–54S.

Davidson MH, Stein EA, Bayes HE, et al. Combination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/day to simvastatin 40 mg/day in hypertriglyceridemic patients: an8-week randomized, doubleblind, placebo-controlled study. Clin Ther 2007; 29: 1354–67.

Harris WS, Kris-Etherton PM, Harris KA. Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults. Curr Atheroscler Rep 2008; 10:503–9.

Harris WS, Gonzales M, Laney N, Sastre A, Borkon AM. Effects of omega-3 fatty acids on heart rate in cardiac transplant recipients. Am J Cardiol 2006; 98:1393–5.

Ventura HO, Milani RV, Lavie CJ, et al. Cycosporine-induced hypertension: efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circulation 1993; 88:11281–5.

Din JN, Harding SA, Valerio CJ, et al. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Atherosclerosis 2008; 197:290–6.

Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits (errata in JAMA 2007; 297:5901). JAMA 2006;296:1885–99.

Madsen T, Schmidt EB, Christensen JH. The effect of ω- fatty acids on C-reactive protein levels in patients with chronic renal failure. J Ren Nutr 2007; 17:258–63.

Zhao G, Etherton TD, Martin KR, Gilles PJ, West SG, Kris-Etherton PM. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr 2007; 85: 385–91.

Conquer JA, Holub BJ. Dietary docosahexaenoic acid as a source of eicosapentaenoic acid in vegetarians and omnivores. Lipids 1997; 32: 341–5.

Park Y, Harris WS. Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance. J Lipid Res 2003; 44: 455– 63.

Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain ω- fatty acids and the risk of sudden death. N Engl J Med 2002;346:1113– 8.

Mori TA, Woodman RJ. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr Opin Clin Nutr Metab Care 2006; 9: 95–104.

Hibbeln JR, Davis JM, Steer C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood. ALSPCA study: an observational cohort study. Lancet 2007; 369:578–85.

Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med 2003; 127:1603–5.

Mervaala E, Muller DN, Schmidt F, et al. Blood pressure-independent effects in rats with human renin and angiotensinogen genes. Hypertension 2000; 35: 587–594.

Xiao HD, Fuchs S, Campbell DJ, et al. Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, cardiac arrhythmia, and sudden death. Am J Pathol 2004; 165: 1019–1032.

Ouvrard-Pascaud A, Sainte-Marie Y, Benitah JP, et al. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Circulation 2005; 111: 3025–3033.

Domenighetti AA, Boixel C, Cefai D, Abriel H, Pedrazzini T. Chronic angiotensin II stimulation in the heart produces an acquired long QT syndrome associated with IK1 potassium current downregulation. J Mol Cell Cardiol 2007; 42: 63–70.

Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of incident atrial fibrillation. Circulation 2004;110:368 –73.

Jump DB. The biochemistry of ω- polyunsaturated fatty acids. J Biol Chem 2002; 277: 8755–8758.

Jain SK, Schuessler RB, Saffitz JE. Mechanisms of delayed electrical uncoupling induced by ischemic preconditioning. Circ Res 2003; 92: 1138– 1144.

Lu T, VanRollins M, Lee HC. Stereospecific activation of cardiac ATPsensitive K(+) channels by poxyeicosatrienoic acids: a structural determinant study. Mol Pharmacol 2002; 62: 1076-1083.

Seubert J, Yang B, Bradbury JA, et al. Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circ Res 2004; 95: 506–514.

Seubert JM, Zeldin DC, Nithipatikom K, Gross GJ. Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/ reperfusion injury. Prostaglandins Other Lipid Mediat 2007; 82: 50–59.

Gross GJ, Hsu A, Falck JR, Nithipatikom K. Mechanisms by which epoxyeicosatrienoic acids (EETs) elicit cardioprotection in rat hearts. J Mol Cell Cardiol 2007; 42: 687–691.

DeBacker G, Ambrosioni E, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2003; 24: 1601–10.

Franz MJ, Bantle JP, Beebe CA, et al. Nutrition principles and recommendations in diabetes. Diabetes Care 2004;27 (Suppl 1): S36–46.

Gardner, C. D. and Kraemer, H. C., Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta-analysis. Arterioscler Thromb Vasc Biol 1995;15: 1917-27.

Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. J Am Med Assn 1996;276: 875-81.

von Schacky C, Baumann K, Angerer P. The effect of ω- fatty acids on coronary atherosclerosis: results from SCIMO, an angiographic study, background and implications. Lipids 2001; 36: S99–S102.

World Health Organization. Diet, Nutrition, and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation. Technical report No. 916. Geneva: World Health Organization, 2003.

How to Cite
Asif M. Role of Polyunsaturated Fatty Acids in Cardiovascular Diseases. J Pharm Care. 2(1):37-44.
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