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DOI: 10.1055/s-0037-1613583
Changes in tissue factor and activated factor XII following an acute myocardial infarction were uninfluenced by high doses of n-3 polyunsaturated fatty acids
Financial support: Axis-Shield, Pronova A/S and Pharmacia A/S, NorwayPublikationsverlauf
Received
04. September 2002
Accepted after revision
16. Januar 2003
Publikationsdatum:
07. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200304/lookinside/thumbnails/10-1055s-0037-1613583-1.jpg)
Summary
Few data exist on the effects of n-3 polyunsaturated fatty acids (PUFAs) on the initiators and endstage products of coagulation following an acute myocardial infarction (MI).
We assessed the long-term effects of n-3 PUFAs on postinfarct variations of tissue factor (TF), activated factor XII (FXIIa) and fibrin monomer (FM), and expected additional statin treatment to modify thrombogenicity.
Acute MI patients (n = 300) were randomly allocated to a high dose of n-3 PUFAs or corn oil for at least one year.
Plasma concentrations of TF, FXIIa and FM were unaffected by n-3 PUFAs as compared to corn oil, and were uninfluenced by additional statin treatment in subgroup analyses. TF decreased (p = 0.0001), while FXIIa increased during the first 6 weeks (p = 0.001). FM remained essentially unchanged during the entire observation period.
In conclusion, TF, FXIIa and FM were unaffected by long-term treatment with high- dosed n-3 PUFAs and by additional statin treatment.
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References
- 1 Libby P. Coronary artery injury and the biology of atherosclerosis: Inflammation, thrombosis, and stabilization. Am J Cardiol 2000; 86 Suppl 3J-9J.
- 2 Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez-Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-9.
- 3 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-50.
- 4 Murano G. The “Hageman” connection: interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation. Am J Hematol 1978; 4: 409-17.
- 5 Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP. Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qr and cytokeratin 1. Thromb Haemost 2001; 85: 119-24.
- 6 Mitropoulos KA, Martin JC, Reeves BEA, Esnouf MP. The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles. Blood 1989; 73: 1525-33.
- 7 Dempfle CE. The use of soluble fibrin in evaluating the acute and chronic hypercoagulable state. Thromb Haemost 1999; 82: 673-83.
- 8 Kim HK, Song KS, Park YS, Yun YS, Shim WH. Changes of plasma tissue factor and tissue factor pathway inhibitor antigen levels and induction of tissue factor expression on the monocytes in coronary artery disease. Cardiology 2000; 93 1-2 31-6.
- 9 Giannitsis E, Siemens HJ, Mitusch R, Tettenborn I, Wiegand U, Schmucker G, Sheikhzadeh A, Stierle U. Prothrombin fragments F1+2, thrombin-antithrombin III complexes, fibrin monomers and fibrinogen in patients with coronary atherosclerosis. Int J Cardiol 1999; 68: 269-74.
- 10 Kohler HP, Carter AM, Stickland MH, Grant PJ. Levels of activated FXII in survivors of myocardial infarction: association with circulating risk factors and extent of coronary artery disease. Thromb Haemost 1998; 79: 14-8.
- 11 Miller GJ, Esnouf MP, Burgess Al, Cooper JA, Mitchell JP. Risk of coronary heart disease and activation of factor XII in middle-aged men. Arterioscler Thromb Vasc Biol 1997; 17: 2103-6.
- 12 Kinsella JE, Lokesh B, Stone RA. Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms. Am J Clin Nutr 1990; 52: 1-28.
- 13 Chu AJ, Moore J. Differential effects of unsaturated fatty acids on modulation of endotoxin-induced tissue factor activation in cultured human leukemia U937 cells. Cell Biochem Funct 1991; 9: 231-8.
- 14 Chu AJ, Walton MA, Prasad JK, Seto A. Blockade by polyunsaturated n-3 fatty acids of endotoxin-induced monocytic tissue factor activation is mediated by the depressed receptor expression in THP-1 cells. J Surg Res 1999; 87: 217-24.
- 15 Ferro D, Basili S, Alessandri C, Cara D, Violi F. Inhibition of tissue-factor- mediated throm-bin generation by simvastatin. Atherosclerosis 2000; 149 (01) 111-6.
- 16 Broijersen A, Hamsten A, Silveira A, Fatah K, Goodall AH, Eriksson M, Angelin B, Hjemdahl P. Gemfibrozil reduces thrombin generation in patients with combined hyperlipidaemia, without influencing plasma fibrino-gen, fibrin gel structure or coagulation factor VII. Thromb Haemost 1996; 76 (02) 171-6.
- 17 Minnema MC, Wittekoek ME, Schoonen-boom N, Kastelein JJ, Hack CE, ten Cate H. Activation of the contact system of coagulation does not contribute to the hemostatic imbalance in hypertriglyceridemia. Arterioscler Thromb Vasc Biol 1999; 19 (10) 2548-53.
- 18 Nilsen DWT, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L. Effects of a high-dose concentrate of n-3 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.
- 19 Nordøy A, Bønaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Int Med 1998; 243: 163-70.
- 20 World Health Organisation. Myocardial infarction community registers. Copenhagen: World Health Organisation. 1976
- 21 Connor SL, Connor WE. Are fish oils beneficial in the prevention and treatment of coronary artery disease?. Am J Clin Nutr 1997; 66 suppl 1020S-31S.
- 22 Esnouf MP, Burgess I A, Dodds AW, Sarphie AF, Miller GJ. A monoclonal antibody raised against human β-factor XIIa which also recog-nizes α-factor XIIa but not factor XII or complexes of factor XIIa with C1 esterase inhibitor. Thromb Haemost 2000; 83: 874-81.
- 23 Lill H, Spannagl M, Trauner A, Schramm W, Schuller D, Ofenloch-Haehnle B, Draeger B, Naser W, Dessauer A. A new immunoassay for soluble fibrin enables a more sensitive detection of the activation state of blood coagulation in vivo. Blood Coagul Fibrinolysis 1993; 4 (01) 97-102.
- 24 Clauss A. Gerinnerungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
- 25 Fleiss JL. The design and analysis of clinical experiments. John Wiley & Sons; 1986
- 26 Zito F, Drummond F, Bujac SR, Esnouf MP, Morrisey JH, Humphries SE, Miller GJ. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation 2000; 102: 2058-62.
- 27 Mitropoulos KA, Miller GJ, Watts GF, Durrington PN. Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency. Atherosclerosis 1992; 95: 119-25.
- 28 Oakley FR, Sanders TA, Miller GJ. Postprandial effects of an oleic acid-rich oil compared with butter on clotting factor VII and fibrinolysis in healthy men. Am J Clin Nutr 1998; 68 (06) 1202-7.
- 29 Tremoli E, Eligini S, Colli S, Maderna P, Rise P, Pazzucconi F, Marangoni F, Sirtori CR, Galli C. N-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes. Arterioscler Thromb 1994; 14: 1600-8.
- 30 Endres S, Ghorbani R, Kelly VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. New Engl J Med 1989; 320: 265-71.
- 31 van den Eijnden M, van Noort JT, Hollaar L, van der Laarse A, Bertina RM. Cholesterol or triglyceride loading of human monocyte-derived macrophages by incubation with modified lipoproteins does not induce tissue factor expression. Arterioscler Thromb Vasc Biol 1999; 19: 384-92.
- 32 Nakamura S, Kamikubo Y, Okajima K, Asakura H, Nakamura K. Plasma tissue factor: Its sensitive assay and characterization. Thromb Haemost 1993; 69: 744 Abstract
- 33 Kagawa H, Komiyama Y, Nakamura S, Miyake T, Miyazaki Y, Hamamoto K, Masuda M, Takahasi H, Nomura S, Fukuhara S. Expression of functional tissue factor on small vesicle of lipopolysaccharide-stimulated human vascular endothelial cells. Thromb Haemost 1997; 203: 820 Abstract
- 34 Krohn CD, Reikeras O, Bjornsen S, Brosstad F. Tissue factor antigen and activity in serum of postoperatively shed blood used for autologous transfusion. Blood Coagul Fibrinolysis 2000; 11: 219-23.
- 35 Soejima H, Ogawa H, Yasue H, Kaikita K, Nishiyama K, Misumi K, Takazoe K, Miyao Y, Yoshimura M, Kugiyama K, Nakamura S, Tsuji I, Kumeda K. Heightened tissue factor associated with tissue factor inhibitor and prognosis in patients with unstable angina. Circulation 1999; 99: 2908-13.
- 36 Misumi K, Ogawa H, Yasue H, Soejima H, Suefuji H, Nishiyama K, Takazoe K, Kugiya-ma K, Tsuji I, Kumeda K, Nakamura S. Comparison of plasma tissue factor levels in unstable and stable angina pectoris. Am J Cardiol 1998; 81: 22-6.
- 37 GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999; 354: 447-55.
- 38 Nilsen DWT, Dalaker K, Nordøy A, Østerud B, Ingebretsen OC, Lyngmo V, Almdahl S, Vaage J, Rasmussen K. Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery. Thromb Haemost 1991; 66: 195-201.
- 39 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-9.
- 40 Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98: 839-44.
- 41 Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in human macrophages: a novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol 1997; 17: 265-72.
- 42 Coppola R, Cristilli P, Cugno M, Ariens RA, Mari D, Mannucci PM. Measurement of activated factor XII in health and disease. Blood Coagul Fibrinolysis 1996; 7: 530-5.
- 43 Stangl K, Laule M, Tenckhoff B. et al. Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction. Am J Cardiol 1998; 81: 841-7.