Omega-3 Studien: Herzbypass

Omega-3: Fakten - Therapie und Dosierung

Herzbypass: 4,0g/Tag EPA & DHA während ca. 1 Jahr nach der Operation
In Fachzeitschriften wurden folgende Artikel über Omega-3 publiziert. Die Liste dieser Publikationen wurde im April 2003 kompiliert und erhebt keinen Anspruch auf Vollständigkeit. Quelle: MEDLINE.
Die Daten dienen als Referenz für Ärzte und Therapeuten, damit eine therapeutische Dosis bei Herzbypass festgelegt werden kann.

n-3 polyunsaturated fatty acids and cardiovascular diseases.
Nordøy A: Department of Medicine, University of Tromsø, Norway; Marchioli R, Arnesen H, Videbaek J
Lipids 2001 36 Suppl:S127-9
An expert round table discussion on the relationship between intake of n-3 polyunsaturated fatty acids (PUFA) mainly of marine sources and coronary heart disease at the 34th Annual Scientific Meeting of European Society for Clinical Investigation came to the following conclusions: 1. Consumption of 1-2 fish meals/wk is associated with reduced coronary heart disease (CHD) mortality. 2. Patients who have experienced myocardial infarction have decreased risk of total, cardiovascular, coronary, and sudden death by drug treatment with 1 g/d of ethylesters of n-3 PUFA, mainly as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The effect is present irrespective of high or low traditional fish intake or simultaneous intake of other drugs for secondary CHD prevention. n-3 PUFA may also be given as fatty fish or triglyceride concentrates. 3. Patients who have experienced coronary artery bypass surgery with venous grafts may reduce graft occlusion rates by administration of 4 g/d of n-3 PUFA. 4. Patients with moderate hypertension may reduce blood pressure by administration of 4 g/d of n-3 PUFA. 5. After heart transplantation, 4 g/d of n-3 PUFA may protect against development of hypertension. 6. Patients with dyslipidemia and or postprandial hyperlipemia may reduce their coronary risk profile by administration of 1-4 g/d of marine n-3 PUFA. The combination with statins seems to be a potent alternative in these patients. 7. There is growing evidence that daily intake of up to 1 energy% of nutrients from plant n-3 PUFA (alpha-linolenic acid) may decrease the risk for myocardial infarction and death in patients with CHD. This paper summarizes the conclusions of an expert panel on the relationship between n-3 PUFA and CHD. The objectives for the experts were to formulate scientifically sound conclusions on the effects of fish in the diet and the administration of marine n-3 PUFA, mainly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), and eventually of plant n-3 PUFA, alpha-linolenic acid (ALA, 18:3n-3), on primary and secondary prevention of CHD. Fish in the diet should be considered as part of a healthy diet low in saturated fats for everybody, whereas additional administration of n-3 PUFA concentrates could be given to specific groups of patients. This workshop was organized on the basis of questions sent to the participants beforehand, on brief introductions by the participants, and finally on discussion and analysis by a group of approximately 40 international scientists in the fields of nutrition, cardiology, epidemiology, lipidology, and thrombosis.

n-3 fatty acids and revascularization procedures.
Arnesen H: Ullevål University Hospital, Oslo, Norway
Lipids 2001 36 Suppl:S103-6
Largely initiated by studies among Greenland Eskimos in the early 1970s, great attention has been given to the possible effects of the very long chain n-3 polyunsaturated fatty acids (PUFA) in a variety of cardiovascular disease states. A series of possibly positive effects on pathogenetic mechanisms in cardiovascular disease has evolved from laboratory studies in cell cultures and animals as well as in humans, focusing mainly on eicosanoid metabolism with reduced activities of platelets and leucocytes, reduced plasma triglycerides and, antiarrhythmic effects in the myocardium. A rationale for a positive effect of very long chain n-3 PUFA in the secondary prophylaxis after revascularization procedures obviously also exists. The positive clinical effects based on prospectively randomized trials are summarized as follows. After coronary artery bypass grafting (CABG), the SHOT study showed statistically significant reduction in angiographic vein graft occlusion in 610 patients after 1 yr with supplementation of 3.4 g/d of highly concentrated very long chain n-3 PUFA. The reduction in occlusion rates was significantly related to the change in the n-3 PUFA concentration in serum phospholipids during the study period with the occlusion rate in the upper quartile of such changes at only approximately 50% of that in the lower quartile. These results were also clearly related to the presence of angina pectoris and occurrence of myocardial infarction after 1 yr. Several studies were conducted in patients after percutaneous transluminal coronary angioplasty (PTCA). By 1993, two meta-analyses indicated a positive effect on the restenosis rate, a significant problem after otherwise successful PTCA. During the late 1990s, three large prospective randomized placebo-controlled angiographic studies were conducted with very long n-3 PUFA 5.1-8.0 g/d, all with completely negative results. Today, therefore, very long chain n-3 PUFA supplementation cannot be recommended to reduce the incidence of restenosis after PTCA. All studies were performed without stenting of the coronary lesion. In the very special revascularization procedure of heart transplantation, evolving hypertension and accelerated atherosclerosis have been major clinical problems. In other studies, positive effects by supplementation with very long chain n-3 PUFA (3.4-5.7 g/d) were obtained on the surrogate end points coronary vasoreactivity to acetylcholine and hypertension, respectively. On the basis of the presently available literature from clinical studies, recommendations for supplementation with very long chain n-3 PUFA can be given to patients after venous CABG (up to 3.4 g/d), and after heart transplantation (3.4-5.7 g/d) but not to patients after traditional PTCA. In fact, data from substudies suggested the possibility that large doses (5.1 g/d) of very long chain n-3 PUFA might be contraindicated because they induce a proinflammatory state in patients under oxidative stress.

Serum Lp(a) lipoprotein levels in patients with coronary artery disease and the influence of long-term n-3 fatty acid supplementation.
Eritsland J: Department of Cardiology, Ullevål Hospital, Oslo, Norway; Arnesen H, Berg K, Seljeflot I, Abdelnoor M
Scand J Clin Lab Invest 1995 Jul 55:295-300
The serum levels of Lp(a) lipoprotein (Lp(a)) were determined preoperatively in 601 patients with coronary artery disease, undergoing bypass operations. Compared with a reference group of 99 apparently healthy individuals, the Lp(a) levels were higher in the patient group (7.7 mg dl-1 vs. 5.1 mg dl-1, p = 0.012). In the patient group, there was a weak, but significant negative correlation between the Lp(a) levels and age (r = -0.10, p = 0.017), and in both groups the women had higher Lp(a) levels than the men. In the patients we found no significant correlations between Lp(a) and other serum lipids or lipoproteins, nor between Lp(a) and variables in the fibrinolytic system. We investigated the long-term effects of supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) on the Lp(a) concentrations. Postoperatively, in a randomized fashion, 280 of the patients received 4 g of an n-3 PUFA concentrate (containing > 85% of long-chain n-3 PUFAs) per day, whereas 269 patients comprised the control group. The fatty acids in serum phospholipids were monitored, and a significant increase in the phospholipid n-3 fatty acids was noted in the n-3 PUFA group, as opposed to the virtually unchanged amounts in the control group. The Lp(a) levels were determined again after 6 months, and, compared with the control group, n-3 PUFA supplementation had no overall effect on the serum Lp(a) levels.

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Long-term effects of n-3 fatty acids on serum lipids and glycaemic control.
Eritsland J: Department of Cardiology, Ullevål Hospital, Oslo, Norway; Seljeflot I, Abdelnoor M, Arnesen H, Torjesen PA
Scand J Clin Lab Invest 1994 Jul 54:273-80

The long-term influence of n-3 polyunsaturated fatty acids (n-3 PUFAs) on serum lipids and glucose homeostasis was studied in a group of non-diabetic, moderately hypertriglyceridaemic patients undergoing coronary artery bypass grafting. They were investigated according to the same procedure before and 6 months after the operation. Following randomization postoperatively, 28 patients received 3.4 g eicosapentaenoic and docosahexaenoic acid per day, whereas 29 patients comprised the control group. The decline in serum triglycerides after 6 months was significantly greater in the n-3 PUFA group than in the control group (median decline, -33.2% vs. -11.1%, p = 0.002), while no group difference was noted in serum total, HDL, or LDL cholesterol levels. Fasting plasma glucose levels decreased less in the n-3 PUFA group compared with the control group (median change, -0.2 mmol l-1 vs. -0.5 mmol l-1, p = 0.054). The corresponding changes in fasting insulin levels were -2 mIU ml-1 in the n-3 PUFA group and no change in the control group (p = 0.039). In both groups combined, the recorded changes in serum triglyceride and serum insulin levels were negatively correlated with the change in serum phospholipid n-3 fatty acids (r = -0.35, p = 0.008 and r = -0.32, p = 0.016, respectively). An oral glucose tolerance test revealed no significant group differences after 6 months, neither in the peak levels, nor in the areas under the curves between 0 and 3h after the glucose load for glucose, insulin, and C-peptide.

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.
Nilsen DW: Dept. of Medicine, University of Tromsø, Norway; Dalaker K, Nordøy A, Osterud B, Ingebretsen OC, Lyngmo V, Almdahl S, Vaage J, Rasmussen K
Thromb Haemost 1991 Aug 66:195-201
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 greater than or equal to 1.6 mmol/l 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 less than 0.05) at end of intervention.

Thromboplastin activities and monocytes in the coronary circulation of reperfused human myocardium. No effect of preoperative treatment with n-3 fatty acids.
Almdahl SM: Department of Surgery, University of Tromsø, Norway; Nilsen DW, Osterud B, Sørlie DG, Vaage J
Scand J Thorac Cardiovasc Surg 1993 27:81-6
In a double-blind study 18 patients were randomized to receive a daily dietary supplement of concentrated ethyl ester compound of n-3 fatty acids or placebo (corn oil) for at least 6 weeks before coronary bypass surgery. Three-fold increase of serum eicosapentaenoic acid and 20% reduction of triglyceride levels were found preoperatively in the n-3 group, while the two groups were similar as regards monocyte and platelet counts, mean platelet volume and monocyte activation as expressed by thromboplastin activities. For determination of transcardiac gradients, coronary sinus and aortic blood were sampled preoperatively 5, 10 and 30 minutes after release of the aortic cross-clamp. In both patient groups the monocyte count was lower in coronary sinus than in aortic blood at 5 and 10 minutes, but the differences were not significant. The platelet counts showed no significant change. In vitro stimulation of monocytes, however, evoked significantly (p < 0.05) less thromboplastin activity in coronary sinus blood than in aortic blood at all three sampling times, without significant intergroup difference. The monocytes most sensitive to activation presumably were trapped in the reperfused myocardium, and this sequestration was not hindered by pretreatment with n-3 fatty acids.

Long-term metabolic effects of n-3 polyunsaturated fatty acids in patients with coronary artery disease.
Eritsland J: Department of Cardiology, Ullevål University Hospital, Oslo, Norway; Arnesen H, Seljeflot I, Høstmark AT
Am J Clin Nutr 1995 Apr 61:831-6
The long-term metabolic effects of n-3 fatty acids were studied in patients with coronary artery disease. They were investigated before and 9 mo after bypass surgery. After postoperative randomization, 260 patients received 4 g fish-oil concentrate/d (approximately 3.4 g eicosapentaenoic and docosahexaenoic acids/d), whereas 251 patients comprised the control group. No group differences in the intake of energy and nutrients, apart from n-3 fatty acids, were discerned from dietary records. Compliance was affirmed by analyses of serum phospholipid fatty acids. Serum triglyceride concentrations were lowered by 19.1% in the fish-oil group, but no influence on the concentrations of cholesterol or apolipoproteins A-I and B-100 was seen. The concentrations of plasma glucose and serum insulin and C-peptide were not influenced by fish oil. The activity of liver enzymes increased slightly, but significantly, in the fish-oil group, whereas no group difference in the serum concentrations of thiobarbituric acid-reactive substances was observed. Thus, no adverse metabolic effects of long-term fish-oil supplementation assumed to be of clinical importance were seen.