Thromb Haemost 1991; 66(02): 195-201
DOI: 10.1055/s-0038-1646389
Review Article
Schattauer GmbH Stuttgart

Influence of a Concentrated Ethylester Compound of n-3 Fatty Acids on Lipids, Platelets and Coagulation in Patients Undergoing Coronary Bypass Surgery

D W T Nilsen
Dept. of Medicine, University of Tromsø, Tromsø, Norway
,
K Dalaker
1   Dept. of Gynaecology, University of Tromsø, Tromsø, Norway
,
A Nordøy
Dept. of Medicine, University of Tromsø, Tromsø, Norway
,
B Østerud
2   Inst. of Medical Biology, University of Tromsø, Tromsø, Norway
,
O C Ingebretsen
3   Dept. of Clinical Chemistry, University of Tromsø, Tromsø, Norway
,
V Lyngmo
Dept. of Medicine, University of Tromsø, Tromsø, Norway
,
S Almdahl
4   Dept. of Surgery, University of Tromsø, Tromsø, Norway
,
J Vaage
4   Dept. of Surgery, University of Tromsø, Tromsø, Norway
,
K Rasmussen
Dept. of Medicine, University of Tromsø, Tromsø, Norway
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 13. November 1990

Accepted 19. Februar 1991

Publikationsdatum:
25. Juli 2018 (online)

Summary

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase.

Only patients with fasting triglyceride (TG) levels ≥1.6 mmol/1 at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively.

A threefold increase (p = 0.0001) of EPA was noted at pre-and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study.

No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p <0.05) at end of intervention. Moreover, a strong positive correlation was noted between PLC-VII and TG (r = 0.77, p = 0.0001).

No significant difference in postoperative bleeding was noted between the two groups of patients.

 
  • References

  • 1 Hjermann I, Velve Byre K, Holme I, Leren P. Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomized trial in healthy men. Lancet 1981; II: 1303-10
  • 2 Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D. Serum cholesterol, blood pressure, and mortality:. 933-6
  • 3 Andersen P, Nilsen DWT, Lyberg Beckmann S, Holme I, Hjermann I. Increased fibrinolytic potential after diet intervention in healthy coronary high-risk individuals. Acta Med Scand 1988; 223: 499-506
  • 4 Hamsten A, Wiman B, de Faire U, Blombôck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63
  • 5 Carlson LA, Bøttiger LE. Risk factors for ischaemic heart disease in men and women. Results of the 19-year follow-up of the Stockholm Prospective Study. Acta Med Scand 1985; 218: 207-11
  • 6 Dyerberg J, Bang HO, Hjørne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 1975; 28: 958-66
  • 7 Bang HO, Dyerberg J, Hjørne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand 1976; 200: 69-73
  • 8 Kromann N, Green A. Epidemiological studies in the Upernarik district, Greenland: incidence of some chronic diseases 1950-1974. Acta Med Scand 1980; 208: 401-6
  • 9 Hirai A, Terano T, Saito H, Tamura Y, Yoshida S. Eicosapentaenoic acid and platelet function in Japanese. In: Nutritional Prevention of Cardiovascular Disease.. Lovenberg W, Yamori Y. (eds) Academic Press, New York: 1984. pp 231-9
  • 10 Kromhout D, Bosschieter EB, de Lezenne CoulanderD. The inverse relation between fish consumption and 20-year survival from coronary heart disease. N Engl J Med 1985; 312: 1205-9
  • 11 Shekelle RB, Missell LV, Oglesby P, Shryock AM, Stamler J. Fish consumption and mortality from coronary heart disease. N Engl J Med 1985; 313: 820
  • 12 Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetham PM, Elwood PC, Deadman NM. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction:. 757-61
  • 13 Weiner BH, Ockene IS, Levine PH, Cuénoud HF, Fisher M, Johnson BF, Daoud AS, Jarmolych J, Hosmer D, Johnson MH, Natale A, Vaudreuil C, Hoogasian JJ. Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model. N Engl J Med 1986; 315: 841-6
  • 14 Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. Reduction in plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med 1985; 312: 1210-6
  • 15 Brox JH, Killie JE, Østerud B, Holme S, Nordøy A. Effects of cod liver oil on platelets and coagulation in familial hypercholesterolemia (Type Ha). Acta Med Scand 1983; 213: 137-44
  • 16 Sullivan DR, Sanders TAB, Trayner IM, Thompson GR. Paradoxical elevation of LDL apoprotein B levels in hypertriglyceridaemic patients and normal subjects ingesting fish oil. Atherosclerosis 1986; 61: 129-34
  • 17 Brox JH, Killie JE, Gunnes S, Nordøy A. The effect of cod liver oil and corn oil on platelets and vessel wall in man. Thromb Haemostas 1981; 46: 604-11
  • 18 Owren PA, Strandli OK. Normotest. Farmakoterapi 1969; 25: 14-26
  • 19 Dalaker K, Janson TL, Johnsen B, Skartlien AH, Prydz H. A simple method for determination of the factor VII-phospholipid complex using Normotest. Thromb Res 1987; 47: 287-93
  • 20 Myrnes BJ, Little C. A simple purification scheme yielding crystalline phospholipase C from Bacillus cereus. . Acta Chem Scand B 1980; 34: 375-7
  • 21 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400
  • 22 Pelzer H, Fuhge P, Bleyl H, Heimburger N. Enzyme immunoassay for determination of human thrombin-antithrombin III complex. Thromb Haemostas 1985; 54: 24 (Abstr)
  • 23 Morse EE, Viswanathan U. Determination of fibrinogen in plasma. Ann Clin Lab Sci 1978; 8: 438-41
  • 24 Burstein M, Scholnick HR, Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970; 11: 583-95
  • 25 Folch J, Less M, Sloan-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509
  • 26 Sharpio SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrica 1965; 52: 591-611
  • 27 Bønaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic acid and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromsø study. N Engl J Med 1990; 322: 795-801
  • 28 Nordøy A, Barstad L, Connor WE, Hatcher L. The absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethylesters and triglycerides by humans.. Am J Clin Nutr 1991; in press.
  • 29 Smith P, Arnesen H, Opstad T, Dahl KH, Eritsland J. Influence of highly concentrated n-3 fatty acids on serum lipids and haemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo. Thromb Res 1989; 53: 467-74
  • 30 Simonsen T, Nordøy A, Sjunneskog C, Lyngmo V. The effect of cod liver oil in two populations with low and high intake of dietary fish. Acta Med Scand 1988; 223: 491-8
  • 31 Leren P. The hypertension-CHD dilemma. Acta Med Scand 1985; 217: 145-7
  • 32 Goodnight SH, Harris WS, Connor WE. The effects of dietary ω3 fatty acids on platelet composition and function in man: A prospective, controlled study. Blood 1981; 58: 880-5
  • 33 Thorngren M, Gustafson A. Effects of 11-week increase in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation. Lancet 1981; II: 1190-3
  • 34 Siess W, Roth P, Scherer B, Kurzman I, Bøhlig B, Weber PC. Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during a mackerel diet. Lancet 1980; I: 441-4
  • 35 Whitaker MO, Wyche A, Fitzpatrick F, Sprecher H, Needleman P. Triene prostaglandins: Prostaglandin D3 and eicosapentaenoic acid as potential antithrombotic substances. Proc Natl Acad Sci USA 1979; 76: 5919-23
  • 36 DeCaterina R, Giannessi D, Mazzone A, Bernini W, Lazzerini G, Maffei S, Cerri M, Salvatore L, Weksler B. Vascular prostacyclin is increased in patients ingesting co-3 polyunsaturated fatty acids before coronary bypass graft surgery. Circulation 1990; 82: 428-38
  • 37 Meade TW, Mellows S, Brozovic M, Miller SG, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thomson SG. Haemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7
  • 38 Dalaker K, Smith P, Arnesen H, Prydz H. Factor VH-phospholipid complex in male survivors of acute myocardial infarction. Acta Med Scand 1987; 222: 111-6
  • 39 Wilhelmsen L, Svôrdsudd K, Korsan Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5
  • 40 Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular death. The Framingham study. JAMA 1987; 258: 1183-6
  • 41 Goodnight Jr SH, Harris WE, Illingworth DR. Polyunsaturated fatty acids, hyperlipidemia and thrombosis. Atherosclerosis 1982; 2: 87-113
  • 42 Høstmark AT, Bjerkedal T, Kierulf P, Flaten H, Ulshagen K. Fish oil and plasma fibrinogen. Br Med J 1988; 297: 180-1
  • 43 Høgman CF, Hedlund K, Sahlstrøm Y. Red blood cell preservation in protein-poor media. III. Protection against in vitro hemolysis. Vox Sang 1981; 41: 274-81