Marine n-3 fatty acids for cardiovascular risk reduction and disease control in rheumatoid arthritis: "Kill two birds with one stone"?

Current Pharmaceutical Design

Volumn 18, Issue 11, 2012, Pages 1531-1542

  Rontoyanni, Victoria G ^a   Sfikakis, Petros P ^a   Kitas, George D ^b,c   Protogerou, Athanase D ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b RUSSELLS HALL HOSPITAL   (United Kingdom)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Cardiovascular risk; DHA; EPA; N 3 fatty acids; Rheumatoid arthritis

Indexed keywords

ANGIOTENSIN II; ARACHIDONIC ACID; ARGININE; C REACTIVE PROTEIN; CARDIOVASCULAR AGENT; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYTOCHROME P450; DOCOSAHEXAENOIC ACID; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; ICOSANOID; ICOSAPENTAENOIC ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; LINOLEIC ACID; LIPID; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NORADRENALIN; OMEGA 3 FATTY ACID; POLYUNSATURATED FATTY ACID; THROMBOXANE; TUMOR NECROSIS FACTOR ALPHA; VERY LOW DENSITY LIPOPROTEIN;

ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ARTERIAL STIFFNESS; ARTHRITIS; ARTICLE; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHEMICAL STRUCTURE; CORONARY ARTERY DISEASE; DIASTOLIC BLOOD PRESSURE; DIET SUPPLEMENTATION; DIETARY INTAKE; DISEASE CONTROL; DYSLIPIDEMIA; FATTY ACID METABOLISM; HEART INFARCTION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; INFLAMMATION; ISCHEMIC HEART DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RHEUMATOID ARTHRITIS; RISK REDUCTION; SECONDARY PREVENTION; SYSTOLIC BLOOD PRESSURE; THROMBOCYTE ACTIVATION; THROMBOSIS;

EID: 84857708439     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212799504722     Document Type: Article

References (195)

1. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 2005; 4: 130-136.
2. Kitas GD, Erb N. Tackling ischaemic heart disease in rheumatoid arthritis. Rheumatology (Oxford) 2003; 42: 607-613.
3. Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59: 1690-1697.
4. Meune C, Touze E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2009; 48: 1309-1313.
5. Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2005; 52: 402-411.
6. Kitas GD, Gabriel SE. Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 2011; 70: 8-14.
7. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
8. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001; 104: 365-372.
9. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 1999; 100: 2124-6.
10. Stevens RJ, Douglas KM, Saratzis AN, Kitas GD. Inflammation and atherosclerosis in rheumatoid arthritis. Expert Rev Mol Med 2005; 7: 1-24.
11. Ridker PM, Cook N. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 2004; 109: 1955-1959.
12. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum 2005; 52: 2293-2299.
13. Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ, et al. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum 2007; 57: 125-132.
14. Peters MJ, Symmons DP, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69: 325-331.
15. John H, Kitas G, Toms T, Goodson N. Cardiovascular co-morbidity in early rheumatoid arthritis. Best Pract Res Clin Rheumatol 2009; 23: 71-82.
16. Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, et al. Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic review. Rheumatology (Oxford) 2008; 47: 239-248.
17. Rosell M, Wesley AM, Rydin K, Klareskog L, Alfredsson L. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology 2009; 20: 896-901.
18. Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 2009; 6: e1000058.
19. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006; 296: 1885-1899.
20. Mozaffarian D. Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Am J Clin Nutr 2008; 87: 1991S-1996S.
21. Harris WS, Mozaffarian D, Lefevre M, et al. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr 2009; 139: 804S-819S.
22. Brenna JT, Salem N, Jr., Sinclair AJ, Cunnane SC. Alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 2009; 80: 85-91.
23. PC. N-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clin Sci (Lond) 2004; 107: 1-11.
24. Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol 2009; 136: 4-16.
25. Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 2008; 197: 12-24.
26. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002; 106: 2747-2757.
27. Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006; 114: 82-96.
28. Cottin SC, Sanders TA, Hall WL. The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc 2011; 70: 215-231.
29. Toms TE, Panoulas VF, Douglas KM, et al. Statin use in rheumatoid arthritis in relation to actual cardiovascular risk: evidence for substantial undertreatment of lipid-associated cardiovascular risk? Ann Rheum Dis 2010; 69: 683-688.
30. Toms TE, Symmons DP, Kitas GD. Dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle and genetic factors. Curr Vasc Pharmacol 2010; 8: 301-326.
31. Cleland LG, Caughey GE, James MJ, Proudman SM. Reduction of cardiovascular risk factors with longterm fish oil treatment in early rheumatoid arthritis. J Rheumatol 2006; 33: 1973-1979.
32. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2003; 23: 27-36.
33. Kremer JM, Bigauoette J, Michalek AV, et al. Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet 1985; 1: 184-187.
34. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 2002; 20: 1493-1499.
35. Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 1999; 34: 253-260.
36. 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.
37. Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 2007; 129: 210-223.
38. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation 2005; 112: 1945-1952.
39. Demaison L, Blet J, Sergiel JP, Gregoire S, Argaud D. Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats. Reprod Nutr Dev 2000; 40: 113-125.
40. Mozaffarian D, Gottdiener JS, Siscovick DS. Intake of tuna or other broiled or baked fish versus fried fish and cardiac structure, function, and hemodynamics. Am J Cardiol 2006; 97: 216-222.
41. Panoulas VF, Douglas KM, Milionis HJ, et al. Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology (Oxford) 2007; 46: 1477-1482.
42. Panoulas VF, Metsios GS, Pace AV, et al. Hypertension in rheumatoid arthritis. Rheumatology (Oxford) 2008; 47: 1286-1298.
43. Sandoo A, Panoulas VF, Toms TE, et al. Anti-TNFalpha therapy may lead to blood pressure reductions through improved endothelium-dependent microvascular function in patients with rheumatoid arthritis. J Hum Hypertens 2011; 25: 699-702.
44. Vita JA, Keaney JF, Jr. Endothelial function: a barometer for cardiovascular risk? Circulation 2002; 106: 640-642.
45. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 2007; 115: 2390-2397.
46. Allen JD, Cobb FR, Kraus WE, Gow AJ. Total nitrogen oxide following exercise testing reflects endothelial function and discriminates health status. Free Radic Biol Med 2006; 41: 740-747.
47. Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, et al. HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis. Am J Med 2003; 114: 647-652.
48. Hansel S, Lassig G, Pistrosch F, Passauer J. Endothelial dysfunction in young patients with long-term rheumatoid arthritis and low disease activity. Atherosclerosis 2003; 170: 177-180.
49. Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 2002; 106: 2184-2187.
50. Kerekes G, Szekanecz Z, Der H, Sandor Z, et al. Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol 2008; 35: 398-406.
51. Stamatelopoulos KS, Kitas GD, Papamichael CM, et al. Atherosclerosis in rheumatoid arthritis versus diabetes: a comparative study. Arterioscler Thromb Vasc Biol 2009; 29: 1702-1708.
52. Vaudo G, Marchesi S, Gerli R, et al. Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 2004; 63: 31-35.
53. Protogerou AD, Zampeli E, Fragiadaki K, Stamatelopoulos K, Papamichael C, Sfikakis PP. A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis. Atherosclerosis 2011; 219: 734-736.
54. Sandoo A, Veldhuijzen van Zanten JJ, Metsios GS, Carroll D, Kitas GD. Vascular function and morphology in rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 2011; 50: 2125-2139.
55. Khan F, Elherik K, Bolton-Smith C, Barr R, Hill A, Murrie I, Belch JJ. The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Cardiovasc Res 2003; 59: 955-962.
56. Shah AP, Ichiuji AM, Han JK, Traina M, El-Bialy A, Meymandi SK, Wachsner RY. Cardiovascular and endothelial effects of fish oil supplementation in healthy volunteers. J Cardiovasc Pharmacol Ther 2007; 12: 213-219.
57. Dangardt F, Osika W, Chen Y, et al. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis 2010; 212: 580-585.
58. de Berrazueta JR, Gomez de Berrazueta JM, Amado Senaris JA, et al. A diet enriched with mackerel (Scomber scombrus)-derived products improves the endothelial function in a senior population (Prevencion de las Enfermedades Cardiovasculares: Estudio Santona--PECES project). Eur J Clin Invest 2009; 39: 165-173.
59. Engler MM, Engler MB, Malloy M, et al. Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int J Clin Pharmacol Ther 2004; 42: 672-679.
60. Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 2000; 35: 265-270.
61. Okumura T, Fujioka Y, Morimoto S, et al. Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability. Am J Med Sci 2002; 324: 247-253.
62. McVeigh GE, Brennan GM, Johnston GD, et al. Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 33-38.
63. Stirban A, Nandrean S, Gotting C, et al. Effects of n-3 fatty acids on macro- and microvascular function in subjects with type 2 diabetes mellitus. Am J Clin Nutr 2010; 91: 808-813.
64. Rizza S, Tesauro M, Cardillo C, et al. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis 2009; 206: 569-574.
65. Schiano V, Laurenzano E, Brevetti G, et al. Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function. Clin Nutr 2008; 27: 241-247.
66. Tagawa H, Shimokawa H, Tagawa T, et al. Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease. J Cardiovasc Pharmacol 1999; 33: 633-640.
67. Tagawa T, Hirooka Y, Shimokawa H, Hironaga, et al. Long-term treatment with eicosapentaenoic acid improves exercise-induced vasodilation in patients with coronary artery disease. Hypertens Res 2002; 25: 823-829.
68. Morgan DR, Dixon LJ, Hanratty CG, et al. Effects of dietary omega-3 fatty acid supplementation on endothelium-dependent vasodilation in patients with chronic heart failure. Am J Cardiol 2006; 97: 547-551.
69. Wright SA, O'Prey FM, McHenry MT, et al. A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus. Ann Rheum Dis 2008; 67: 841-848.
70. Mori TA, Watts GF, Burke V, Hilme E, Puddey IB, Beilin LJ. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation 2000; 102: 1264-1269.
71. Chin JP, Gust AP, Nestel PJ, Dart AM. Marine oils dose-dependently inhibit vasoconstriction of forearm resistance vessels in humans. Hypertension 1993; 21: 22-28.
72. Kenny D, Warltier DC, Pleuss JA, Hoffmann RG, Goodfriend TL, Egan BM. Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men. Am J Cardiol 1992; 70: 1347-1352.
73. Walser B, Giordano RM, Stebbins CL. Supplementation with omega-3 polyunsaturated fatty acids augments brachial artery dilation and blood flow during forearm contraction. Eur J Appl Physiol 2006; 97: 347-354.
74. Sanders TA, Hall WL, Maniou Z, Lewis F, Seed PT, Chowienczyk PJ. Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial. Am J Clin Nutr 2011; 94: 973-980.
75. West SG, Hecker KD, Mustad VA, et al. Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes. Diabetologia 2005; 48: 113-122.
76. Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond) 2008; 114: 679-686.
77. Fahs CA, Yan H, Ranadive S, et al. The effect of acute fish-oil supplementation on endothelial function and arterial stiffness following a high-fat meal. Appl Physiol Nutr Metab 2010; 35: 294-302.
78. Newens KJ, Thompson AK, Jackson KG, Wright J, Williams CM. DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity. Am J Clin Nutr 2011; 94: 742-748.
79. Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TA. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high fat meals containing DHA or EPA. Br J Nutr In Press.
80. Hall WL, Sanders KA, Sanders TA, Chowienczyk PJ. A high-fat meal enriched with eicosapentaenoic acid reduces postprandial arterial stiffness measured by digital volume pulse analysis in healthy men. J Nutr 2008; 138: 287-291.
81. Chong MF, Lockyer S, Saunders CJ, Lovegrove JA. Long chain n-3 PUFA-rich meal reduced postprandial measures of arterial stiffness. Clin Nutr 2010; 29: 678-681.
82. Li Q, Zhang Q, Wang M, et al. Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae. Arch Biochem Biophys 2007; 466: 250-259.
83. Li Q, Zhang Q, Wang M, et al. Eicosapentaenoic acid modifies lipid composition in caveolae and induces translocation of endothelial nitric oxide synthase. Biochimie 2007; 89: 169-177.
84. Abeywardena MY, Fischer S, Schweer H, Charnock JS. In vivo formation of metabolites of prostaglandins I2 and I3 in the marmoset monkey (Callithrix jacchus) following dietary supplementation with tuna fish oil. Biochim Biophys Acta 1989; 1003: 161-166.
85. DeCaterina R, Giannessi D, Mazzone A, et al. Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery. Circulation 1990; 82: 428-438.
86. Matsumoto T, Nakayama N, Ishida K, Kobayashi T, Kamata K. Eicosapentaenoic acid improves imbalance between vasodilator and vasoconstrictor actions of endothelium-derived factors in mesenteric arteries from rats at chronic stage of type 2 diabetes. J Pharmacol Exp Ther 2009; 329: 324-334.
87. Boku K, Ohno T, Saeki T, et al. Adaptive cytoprotection mediated by prostaglandin I(2) is attributable to sensitization of CRGP-containing sensory nerves. Gastroenterology 2001; 120: 134-43.
88. Takeuchi K, Kato S, Takeeda M, Ogawa Y, Nakashima M, Matsumoto M. Facilitation by endogenous prostaglandins of capsaicin-induced gastric protection in rodents through EP2 and IP receptors. J Pharmacol Exp Ther 2003; 304: 1055-1062.
89. Hishinuma T, Yamazaki T, Mizugaki M. Effects of long-term supplementation of eicosapentanoic and docosahexanoic acid on the 2-, 3-series prostacyclin production by endothelial cells. Prostaglandins Other Lipid Mediat 1999; 57: 333-340.
90. Egert S, Stehle P. Impact of n-3 fatty acids on endothelial function: results from human interventions studies. Curr Opin Clin Nutr Metab Care 2011; 14: 121-131.
91. Cazzola R, Russo-Volpe S, Miles EA, et al. Age- and dose-dependent effects of an eicosapentaenoic acid-rich oil on cardiovascular risk factors in healthy male subjects. Atherosclerosis 2007; 193: 159-167.
92. Miles EA, Thies F, Wallace FA, et al. Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clin Sci (Lond) 2001; 100: 91-100.
93. Thies F, Miles EA, Nebe-von-Caron G, et al. Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 2001; 36: 1183-1193.
94. Maki-Petaja KM, Hall FC, Booth AD, et al. Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy. Circulation 2006; 114: 1185-1192.
95. Pieringer H, Stuby U, Pohanka E, Biesenbach G. Arterial stiffness in a muscular artery in women with longstanding rheumatoid arthritis compared with healthy controls and patients with traditional cardiovascular risk factors. Rheumatol Int 2010; 30: 1335-1339.
96. Roman MJ, Devereux RB, Schwartz JE, et al. Arterial stiffness in chronic inflammatory diseases. Hypertension 2005; 46: 194-199.
97. Tanaka K, Inaba M, Goto H, et al. Paraarticular trabecular bone loss at the ultradistal radius and increased arterial stiffening in postmenopausal patients with rheumatoid arthritis. J Rheumatol 2006; 33: 652-658.
98. Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588-2605.
99. Hamazaki T, Urakaze M, Sawazaki S, Yamazaki K, Taki H, Yano S. Comparison of pulse wave velocity of the aorta between inhabitants of fishing and farming villages in Japan. Atherosclerosis 1988; 73: 157-160.
100. McVeigh GE, Brennan GM, Cohn JN, Finkelstein SM, Hayes RJ, Johnston GD. Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb 1994; 14: 1425-1429.
101. Mita T, Watada H, Ogihara T, et al. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes. Atherosclerosis 2007; 191: 162-167.
102. Nestel P, Shige H, Pomeroy S, Cehun M, Abbey M, Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr 2002; 76: 326-330.
103. Satoh N, Shimatsu A, Kotani K, et al. Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decreased serum amyloid A-LDL in metabolic syndrome. Hypertens Res 2009; 32: 1004-1008.
104. Tomiyama H, Takazawa K, Osa S, et al. Do eicosapentaenoic acid supplements attenuate age-related increases in arterial stiffness in patients with dyslipidemia?: A preliminary study. Hypertens Res 2005; 28: 651-655.
105. Wang S, Ma AQ, Song SW, Quan QH, Zhao XF, Zheng XH. Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients. Eur J Clin Nutr 2008; 62: 1426-1431.
106. Bots ML. Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies. Curr Med Res Opin 2006; 22: 2181-2190.
107. Gonzalez-Juanatey C, Llorca J, Testa A, Revuelta J, Garcia-Porrua C, Gonzalez-Gay MA. Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine (Baltimore) 2003; 82: 407-413.
108. Park YB, Ahn CW, Choi HK, et al. Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 2002; 46: 1714-1719.
109. van Sijl AM, Peters MJ, Knol DK, et al. Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum 2011; 40: 389-397.
110. Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol 2010; 30: 1014-1026.
111. Yamada T, Strong JP, Ishii T, et al. Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan. Atherosclerosis 2000; 153: 469-481.
112. Erkkila AT, Lichtenstein AH, Mozaffarian D, Herrington DM. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr 2004; 80: 626-632.
113. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999; 130: 554-562.
114. Angerer P, Kothny W, Stork S, von Schacky C. Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Cardiovasc Res 2002; 54: 183-190.
115. Sacks FM, Stone PH, Gibson CM, Silverman DI, Rosner B, Pasternak RC. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995; 25: 1492-1498.
116. Ebbesson SO, Roman MJ, Devereux RB, et al. Consumption of omega-3 fatty acids is not associated with a reduction in carotid atherosclerosis: the Genetics of Coronary Artery Disease in Alaska Natives study. Atherosclerosis 2008; 199: 346-353.
117. He K, Liu K, Daviglus ML, et al. Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis. Am J Clin Nutr 2008; 88: 1111-1118.
118. Hino A, Adachi H, Toyomasu K, et al. Very long chain N-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography. Atherosclerosis 2004; 176: 145-149.
119. Baldassarre D, Amato M, Eligini S, et al. Effect of n-3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: a double-blind pilot study in primary prevention. Ann Med 2006; 38: 367-375.
120. Hjerkinn EM, Abdelnoor M, Breivik L, et al. Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil 2006; 13: 325-333.
121. Thies F, Garry JM, Yaqoob P, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 2003; 361: 477-485.
122. Cawood AL, Ding R, Napper FL, et al. 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 2010; 212: 252-259.
123. Aubry MC, Maradit-Kremers H, Reinalda MS, Crowson CS, Edwards WD, Gabriel SE. Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis. J Rheumatol 2007; 34: 937-942.
124. Douglas KM, Pace AV, Treharne GJ, et al. Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome. Ann Rheum Dis 2006; 65: 348-353.
125. Din JN, Harding SA, Valerio CJ, et al. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Atherosclerosis 2008; 197: 290-296.
126. Hartweg J, Farmer AJ, Holman RR, Neil A. Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes. Curr Opin Lipidol 2009; 20: 30-38.
127. Mori TA, Beilin LJ, Burke V, Morris J, Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997; 17: 279-286.
128. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 2006; 116: 4-15.
129. Proudman SM, Cleland LG, James MJ. Dietary omega-3 fats for treatment of inflammatory joint disease: efficacy and utility. Rheum Dis Clin North Am 2008; 34: 469-479.
130. Gasparyan AY, Stavropoulos-Kalinoglou A, Mikhailidis DP, Douglas KM, Kitas GD. Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications. Rheumatol Int 2011; 31: 153-164.
131. Gasparyan AY, Stavropoulos-Kalinoglou A, Toms TE, Douglas KM, Kitas GD. Association of mean platelet volume with hypertension in rheumatoid arthritis. Inflamm Allergy Drug Targets 2010; 9: 45-50.
132. Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum 2005; 52: 412-420.
133. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol 2003; 30: 36-40.
134. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 2004; 109: 2705-2711.
135. Leon H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT. Effect of fish oil on arrhythmias and mortality: systematic review. BMJ 2008; 337: a2931.
136. Zhao YT, Chen Q, Sun YX, Li XB, Zhang P, Xu Y, Guo JH. Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: a meta-analysis of randomized controlled trials. Ann Med 2009; 41: 301-310.
137. Kris-Etherton PM, Harris WS, Appel LJ. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 2003; 23: 151-152.
138. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999; 354: 447-455.
139. Marchioli R, Barzi F, Bomba E, et al. 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 2002; 105: 1897-1903.
140. Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ 2010; 341: c6273.
141. Kromhout D, Giltay EJ, Geleijnse JM. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010; 363: 2015-2026.
142. Rauch B, Schiele R, Schneider S, et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation 2010; 122: 2152-2159.
143. De Caterina R. n-3 fatty acids in cardiovascular disease. N Engl J Med 2011; 364: 2439-2450.
144. Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010; 376: 540-550.
145. Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009; 32: 365-372.
146. 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; 369: 1090-1098.
147. Belin RJ, Greenland P, Martin L, et al. Fish Intake and the Risk of Incident Heart Failure: The Women's Health Initiative. Circ Heart Fail 2011.
148. 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.
149. Yamagishi K, Iso H, Date C, et al. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol 2008; 52: 988-996.
150. Ghio S, Scelsi L, Latini R, et al. Effects of n-3 polyunsaturated fatty acids and of rosuvastatin on left ventricular function in chronic heart failure: a substudy of GISSI-HF trial. Eur J Heart Fail 2010; 12: 1345-1353.
151. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1231-1239.
152. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1223-1230.
153. He K, Song Y, Daviglus ML, et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke 2004; 35: 1538-1542.
154. Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006; 332: 752-760.
155. Tanaka K, Ishikawa Y, Yokoyama M, et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 2008; 39: 2052-2058.
156. Calder PC. N-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006; 83: 1505S-1519S.
157. Calder PC. Immunomodulation by omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 2007; 77: 327-335.
158. Bingham CO, 3rd. The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation. J Rheumatol Suppl 2002; 65: 3-9.
159. Feldmann M, Maini RN. The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 1999; 2: 3-7.
160. Sijben JW, Calder PC. Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease. Proc Nutr Soc 2007; 66: 237-259.
161. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8: 349-361.
162. Kohli P, Levy BD. Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol 2009; 158: 960-971.
163. Lima-Garcia J, Dutra R, da Silva K, Motta E, Campos M, Calixto J. The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. Br J Pharmacol 2011; 164: 278-293.
164. Serhan CN, Yang R, Martinod K, et al. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 2009; 206: 15-23.
165. Calder PC. Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease' PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc 2008; 67: 409-418.
166. Cleland LG, James MJ, Proudman SM. The role of fish oils in the treatment of rheumatoid arthritis. Drugs 2003; 63: 845-853.
167. James M, Proudman S, Cleland L. Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc 2010; 69: 316-323.
168. James MJ, Proudman SM, Cleland LG. Dietary n-3 fats as adjunctive therapy in a prototypic inflammatory disease: issues and obstacles for use in rheumatoid arthritis. Prostaglandins Leukot Essent Fatty Acids 2003; 68: 399-405.
169. Fortin PR, Lew RA, Liang MH, et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 1995; 48: 1379-1390.
170. MacLean CH, Mojica WA, Morton SC, et al. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid Rep Technol Assess 2004. Available at http://www.ahrq.gov/clinic/epcsums/o3lipidsum.pdf(accessed October 10, 2011).
171. Cleland LG, French JK, Betts WH, Murphy GA, Elliott MJ. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 1988; 15: 1471-1475.
172. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum 1990; 33: 810-820.
173. Kremer JM, Jubiz W, Michalek A, et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Ann Intern Med 1987; 106: 497-503.
174. Sperling RI, Weinblatt M, Robin JL, et al. Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arthritis Rheum 1987; 30: 988-997.
175. van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990; 49: 76-80.
176. Caughey GE, James MJ, Proudman SM, Cleland LG. Fish oil supplementation increases the cyclooxygenase inhibitory activity of paracetamol in rheumatoid arthritis patients. Complement Ther Med 2010; 18: 171-174.
177. Espersen GT, Grunnet N, Lervang HH, et al. Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids. Clin Rheumatol 1992; 11: 393-395.
178. Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum 1995; 38: 1107-1114.
179. Sundrarjun T, Komindr S, Archararit N, et al. Effects of n-3 fatty acids on serum interleukin-6, tumour necrosis factor-alpha and soluble tumour necrosis factor receptor p55 in active rheumatoid arthritis. J Int Med Res 2004; 32: 443-454.
180. Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 2005; 21: 131-136.
181. Remans PH, Sont JK, Wagenaar LW, et al. Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects. Eur J Clin Nutr 2004; 58: 839-45.
182. Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH. Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthritis Rheum 1990; 33: 1416-1419.
183. Stamp LK, James MJ, Cleland LG. Diet and rheumatoid arthritis: a review of the literature. Semin Arthritis Rheum 2005; 35: 77-94.
184. Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007; 99: 44C-46C.
185. Melanson SF, Lewandrowski EL, Flood JG, Lewandrowski KB. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med 2005; 129: 74-77.
186. Department of Health and Human Services, US Food and Drug Administration. Substances Affirmed as Generally Recognized as Safe: Menhaden Oil. In: ed.^eds. Federal Register, 1997; pp. 30751-30757.
187. Department of Health and Human Services, US Food and Drug Administration. Agency response letter GRAS notice no. GRN 000102. In: ed.^eds., 2002.
188. Stoof TJ, Korstanje MJ, Bilo HJ, Starink TM, Hulsmans RF, Donker AJ. Does fish oil protect renal function in cyclosporin-treated psoriasis patients? J Intern Med 1989; 226: 437-441.
189. Mitsugi K, Nakamura T, Kashiwabara N, et al. Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet: comparative study with a casein-containing diet. Oncol Rep 2004; 12: 41-45.
190. Cleland LG, James MJ, Proudman SM. Fish oil: what the prescriber needs to know. Arthritis Res Ther 2006; 8: 202.
191. Dawczynski C, Schubert R, Hein G, et al. Long-term moderate intervention with n-3 long-chain PUFA-supplemented dairy products: effects on pathophysiological biomarkers in patients with rheumatoid arthritis. Br J Nutr 2009; 101: 1517-1526.
192. Volker D, Fitzgerald P, Major G, Garg M. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 2000; 27: 2343-2346.
193. Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Arthritis Rheum 1994; 37: 824-829.
194. Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R, Mikkelsen K, Forre O. Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. J Rheumatol 1992; 19: 1531-1536.
195. Nielsen GL, Faarvang KL, Thomsen BS, et al. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992; 22: 687-691.