1.Rader DJ & Daugherty A (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913.
3.Lloyd-Jones D, Adams R, Carnethon M et al. (2009) Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119, 480–486.
4.Sanz J & Fayad ZA (2008) Imaging of atherosclerotic cardiovascular disease. Nature 451, 953–957.
5.van Dijk RA, Virmani R, von der Thusen JH et al. (2010) The natural history of aortic atherosclerosis: a systematic histopathological evaluation of the peri-renal region. Atherosclerosis 210, 100–106.
6.Danesh J, Wheeler JG, Hirschfield GM et al. (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350, 1387–1397.
7.Burdge GC & Calder PC (2005) Plasma cytokine response during the postprandial period: a potential causal process in vascular disease? Br J Nutr 93, 3–9.
8.Sinclair HM (1956) Deficiency of essential fatty acids and atherosclerosis, etc. Lancet 270, 381–383.
9.Dyerberg J, Bang HO & Hjorne N (1975) Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 28, 958–966.
10.Menotti A, Kromhout D, Blackburn H et al. (1999) Food intake patterns and 25-year mortality from coronary heart disease: cross-cultural correlations in the Seven Countries Study. The Seven Countries Study Research Group. Eur J Epidemiol 15, 507–515.
11.Holub BJ (2002) Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. Can Med Assoc J 166, 608–615.
12.Lee KW & Lip GY (2003) The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease. Q J Med 96, 465–480.
13.Dolecek TA (1992) Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med 200, 177–182.
14.Albert CM, Campos H, Stampfer MJ et al. (2002) Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 346, 1113–1118.
15.Hu FB, Bronner L, Willett WC et al. (2002) Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA 287, 1815–1821.
16.Breslow JL (2006) n-3 Fatty acids and cardiovascular disease. Am J Clin Nutr 83, 1477S–1482S.
17.Harris WS (2007) Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res 55, 217–223.
18.Psota TL, Gebauer SK & Kris-Etherton P (2006) Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol 98, 3i–18i.
19.Marik PE & Varon J (2009) Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 32, 365–372.
20.Russo GL (2009) Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 77, 937–946.
21.Vrablik M, Prusikova M, Snejdrlova M et al. (2009) Omega-3 fatty acids and cardiovascular disease risk: do we understand the relationship? Physiol Res 58, Suppl. 1, S19–S26.
22.Rocquelin G, Guenot L, Justrabo E et al. (1985) Fatty acid composition of human heart phospholipids: data from 53 biopsy specimens. J Mol Cell Cardiol 17, 769–773.
23.Kelley DS, Bartolini GL, Newman JW et al. (2006) Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid. Prostaglandins Leukot Essent Fatty Acids 74, 331–338.
24.Cao J, Schwichtenberg KA, Hanson NQ et al. (2006) Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem 52, 2265–2272.
25.Arterburn LM, Hall EB & Oken H (2006) Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 83, 1467S–1476S.
26.Brenna JT, Salem N Jr, Sinclair AJ et al. (2009) Alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80, 85–91.
27.Holub BJ (2009) Docosahexaenoic acid (DHA) and cardiovascular disease risk factors. Prostaglandins Leukot Essent Fatty Acids 81, 199–204.
28.Ryan AS, Keske MA, Hoffman JP et al. (2009) Clinical overview of algal-docosahexaenoic acid: effects on triglyceride levels and other cardiovascular risk factors. Am J Ther 16, 183–192.
29.Skulas-Ray AC, Kris-Etherton PM, Harris WS et al. (2011) Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr 93, 243–252.
30.Grimsgaard S, Bonaa KH, Hansen JB et al. (1997) Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr 66, 649–659.
31.Mori TA, Burke V, Puddey IB et al. (2000) Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 71, 1085–1094.
32.Rambjor GS, Walen AI, Windsor SL et al. (1996) Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids 31, Suppl., S45–S49.
33.Hansen JB, Grimsgaard S, Nilsen H et al. (1998) Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on fatty acid absorption, incorporation into serum phospholipids and postprandial triglyceridemia. Lipids 33, 131–138.
34.Cottin SC, Sanders TA & Hall WL (2011) The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc 70, 215–231.
35.Suzukawa M, Abbey M, Howe PR et al. (1995) Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages. J Lipid Res 36, 473–484.
36.Calabresi L, Donati D, Pazzucconi F et al. (2000) Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses. Atherosclerosis 148, 387–396.
37.Thomas TR, Smith BK, Donahue OM et al. (2004) Effects of omega-3 fatty acid supplementation and exercise on low-density lipoprotein and high-density lipoprotein subfractions. Metabolism 53, 749–754.
38.Griffin MD, Sanders TA, Davies IG et al. (2006) Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45–70 y: the OPTILIP Study. Am J Clin Nutr 84, 1290–1298.
39.Mostad IL, Bjerve KS, Lydersen S et al. (2008) Effects of marine n-3 fatty acid supplementation on lipoprotein subclasses measured by nuclear magnetic resonance in subjects with type II diabetes. Eur J Clin Nutr 62, 419–429.
40.Egert S, Kannenberg F, Somoza V et al. (2009) Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 139, 861–868.
41.Woodman RJ, Mori TA, Burke V et al. (2003) Docosahexaenoic acid but not eicosapentaenoic acid increases LDL particle size in treated hypertensive type 2 diabetic patients. Diabetes Care 26, 253.
42.Theobald HE, Chowienczyk PJ, Whittall R et al. (2004) LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women. Am J Clin Nutr 79, 558–563.
43.Engler MM, Engler MB, Malloy MJ et al. (2005) Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study). Am J Cardiol 95, 869–871.
44.Kelley DS, Siegel D, Vemuri M et al. (2007) Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr 86, 324–333.
45.Neff LM, Culiner J, Cunningham-Rundles S et al. (2011) Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr 141, 207–213.
46.Buckley R, Shewring B, Turner R et al. (2004) Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects. Br J Nutr 92, 477–483.
47.Nakajima K, Nakano T & Tanaka A (2006) The oxidative modification hypothesis of atherosclerosis: the comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma. Clin Chim Acta 367, 36–47.
48.Hamazaki K, Itomura M, Huan M et al. (2003) n-3 Long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans. Lipids 38, 353–358.
49.Kelley DS, Siegel D, Vemuri M et al. (2008) Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men. J Nutr 138, 30–35.
50.Kelm M (2002) Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects. Am J Physiol Heart Circ Physiol 282, H1–H5.
51.Engler MM, Engler MB, Malloy M et al. (2004) Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int J Clin Pharmacol Ther 42, 672–679.
52.Theobald HE, Goodall AH, Sattar N et al. (2007) Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. J Nutr 137, 973–978.
53.Okumura T, Fujioka Y, Morimoto S et al. (2002) Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability. Am J Med Sci 324, 247–253.
54.Sekikawa A, Curb JD, Ueshima H et al. (2008) Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese–American, and white men: a cross-sectional study. J Am Coll Cardiol 52, 417–424.
55.Sacks FM, Stone PH, Gibson CM et al. (1995) Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 25, 1492–1498.
56.von Schacky C, Angerer P, Kothny W et al. (1999) The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 130, 554–562.
57.Angerer P, Kothny W, Stork S et al. (2002) Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Cardiovasc Res 54, 183–190.
58.Anderson JS, Nettleton JA, Herrington DM et al. (2010) Relation of omega-3 fatty acid and dietary fish intake with brachial artery flow-mediated vasodilation in the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr 92, 1204–1213.
59.He K, Liu K, Daviglus ML et al. (2008) Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis. Am J Clin Nutr 88, 1111–1118.
60.Erkkila AT, Matthan NR, Herrington DM et al. (2006) Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD. J Lipid Res 47, 2814–2819.
61.Abe Y, El-Masri B, Kimball KT et al. (1998) Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. Arterioscler Thromb Vasc Biol 18, 723–731.
62.Nomura S, Kanazawa S & Fukuhara S (2003) Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with type 2 diabetes mellitus. J Diabetes Complications 17, 153–159.
63.Eschen O, Christensen JH, De Caterina R et al. (2004) Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids. Nutr Metab Cardiovasc Dis 14, 180–185.
64.Thies F, Garry JM, Yaqoob P et al. (2003) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477–485.
65.Kelley DS, Siegel D, Fedor DM et al. (2009) DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr 139, 495–501.
66.De Caterina R, Liao JK & Libby P (2000) Fatty acid modulation of endothelial activation. Am J Clin Nutr 71, 213S–223S.
67.Cawood AL, Ding R, Napper FL et al. (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.
68.Cicero AF, Ertek S & Borghi C (2009) Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management. Curr Vasc Pharmacol 7, 330–337.
69.Mori TA & Woodman RJ (2006) The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr Opin Clin Nutr Metab Care 9, 95–104.
70.Mori TA, Bao DQ, Burke V et al. (1999) Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension 34, 253–260.
71.Woodman RJ, Mori TA, Burke V et al. (2002) Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 76, 1007–1015.
72.Keller DD, Jurgilas S & Perry B (2007) Docosahexaenoic acid (DHA) lowers triglyceride levels and improves low density lipoprotein particle size in a statin-treated cardiac risk population. J Clin Lipidol 1, 151.
73.Conquer JA & Holub BJ (1998) Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background. J Lipid Res 39, 286–292.
74.Geppert J, Kraft V, Demmelmair H et al. (2006) Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial. Br J Nutr 95, 779–786.
75.Stark KD & Holub BJ (2004) Differential eicosapentaenoic acid elevations and altered cardiovascular disease risk factor responses after supplementation with docosahexaenoic acid in postmenopausal women receiving and not receiving hormone replacement therapy. Am J Clin Nutr 79, 765–773.
76.Grimsgaard S, Bonaa KH, Hansen JB et al. (1998) Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Am J Clin Nutr 68, 52–59.
77.Calder PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83, 1505S–1519S.
78.Calder PC (2009) Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie 91, 791–795.
79.Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107, 363–369.
80.Daviglus ML, Stamler J, Orencia AJ et al. (1997) Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med 336, 1046–1053.
81.Zhang J, Sasaki S, Amano K et al. (1999) Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study. Prev Med 28, 520–529.
82.Zampelas A, Panagiotakos DB, Pitsavos C et al. (2005) Fish consumption among healthy adults is associated with decreased levels of inflammatory markers related to cardiovascular disease: the ATTICA study. J Am Coll Cardiol 46, 120–124.
83.Niu K, Hozawa A, Kuriyama S et al. (2006) Dietary long-chain n-3 fatty acids of marine origin and serum C-reactive protein concentrations are associated in a population with a diet rich in marine products. Am J Clin Nutr 84, 223–229.
84.Murakami K, Sasaki S, Takahashi Y et al. (2008) Total n-3 polyunsaturated fatty acid intake is inversely associated with serum C-reactive protein in young Japanese women. Nutr Res 28, 309–314.
85.Madsen T, Skou HA, Hansen VE et al. (2001) C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol 88, 1139–1142.
86.Pischon T, Hankinson SE, Hotamisligil GS et al. (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108, 155–160.
87.Lopez-Garcia E, Schulze MB, Manson JE et al. (2004) Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 134, 1806–1811.
88.Klein-Platat C, Drai J, Oujaa M et al. (2005) Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. Am J Clin Nutr 82, 1178–1184.
89.Ferrucci L, Cherubini A, Bandinelli S et al. (2006) Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 91, 439–446.
90.Kelley DS, Taylor PC, Nelson GJ et al. (1998) Dietary docosahexaenoic acid and immunocompetence in young healthy men. Lipids 33, 559–566.
91.Thies F, Miles EA, Nebe-von-Caron G et al. (2001) 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 36, 1183–1193.
92.Kew S, Banerjee T, Minihane AM et al. (2003) Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Am J Clin Nutr 77, 1287–1295.
93.Mori TA, Woodman RJ, Burke V et al. (2003) Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radical Biol Med 35, 772–781.
94.Kelley DS, Taylor PC, Nelson GJ et al. (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34, 317–324.
95.Stanke-Labesque F, Moliere P, Bessard J et al. (2008) Effect of dietary supplementation with increasing doses of docosahexaenoic acid on neutrophil lipid composition and leukotriene production in human healthy volunteers. Br J Nutr 100, 829–833.
96.Yusof HM, Miles EA & Calder P (2008) Influence of very long-chain n-3 fatty acids on plasma markers of inflammation in middle-aged men. Prostaglandins Leukot Essent Fatty Acids 78, 219–228.
97.Sierra S, Lara-Villoslada F, Comalada M et al. (2008) Dietary eicosapentaenoic acid and docosahexaenoic acid equally incorporate as decosahexaenoic acid but differ in inflammatory effects. Nutrition 24, 245–254.
98.Kaikkonen J, Tuomainen TP, Nyyssonen K et al. (2004) C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo. Scand J Clin Lab Invest 64, 457–468.
99.Spiteller G (2005) The relation of lipid peroxidation processes with atherogenesis: a new theory on atherogenesis. Mol Nutr Food Res 49, 999–1013.
100.Yoshida Y & Niki E (2006) Bio-markers of lipid peroxidation in vivo: hydroxyoctadecadienoic acid and hydroxycholesterol. Biofactors 27, 195–202.
101.Spiteller G (2007) The important role of lipid peroxidation processes in aging and age dependent diseases. Mol Biotechnol 37, 5–12.
102.Leonarduzzi G, Arkan MC, Basaga H et al. (2000) Lipid oxidation products in cell signaling. Free Radical Biol Med 28, 1370–1378.
103.Tang DG, La E, Kern J et al. (2002) Fatty acid oxidation and signaling in apoptosis. Biol Chem 383, 425–442.
104.Niki E, Yoshida Y, Saito Y et al. (2005) Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 338, 668–676.
105.Yoshida Y, Saito Y, Hayakawa M et al. (2007) Levels of lipid peroxidation in human plasma and erythrocytes: comparison between fatty acids and cholesterol. Lipids 42, 439–449.
106.Harats D, Dabach Y, Hollander G et al. (1991) Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. Atherosclerosis 90, 127–139.
107.Meydani M, Natiello F, Goldin B et al. (1991) Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J Nutr 121, 484–491.
108.Palozza P, Sgarlata E, Luberto C et al. (1996) n-3 fatty acids induce oxidative modifications in human erythrocytes depending on dose and duration of dietary supplementation. Am J Clin Nutr 64, 297–304.
109.Egert S, Somoza V, Kannenberg F et al. (2007) Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr 61, 314–325.
110.Parra D, Bandarra NM, Kiely M et al. (2007) Impact of fish intake on oxidative stress when included into a moderate energy-restricted program to treat obesity. Eur J Nutr 46, 460–467.
111.Calzada C, Colas R, Guillot N et al. (2010) Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men. Atherosclerosis 208, 467–472.