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https://doi.org/10.3389/fcvm.2017.00041 Background: Fish is the natural dietary source of vitamin D. Reports on the influence of purified omega-3 fatty acids on its uptake are scarce. Objectives: We investigated the impact of a purified high-dose omega-3 compound compared to corn oil on 25-hydroxyvitamin D [25(OH)D] levels following an acute myocardial infarction. Methods: 228 patients were randomized 1:1 to receive a daily dose of either 4 g omega-3 (OMACOR®) or an equal dose of corn oil, administered double-blindly for 12 months. Total omega-3 and omega-6 measurements were available in 40 randomly picked patients. Results: There was no significant intergroup difference in 25(OH)D changes at 12 months follow-up (p = 0.12), but there was a minor statistical significant intragroup increase in 25(OH)D in both intervention arms (p < 0.001 for n-3 polyunsaturated fatty acids and p = 0.013 for corn oil, respectively). A positive correlation was noted between 25(OH)D and omega-3 prior to inclusion; r = 0.418, p = 0.007, attenuated at 12 months by purified omega-3 intervention; r = 0.021, p = 0.93. No positive correlation was observed between omega-6 and 25(OH)D. Conclusion: Long-term treatment with a high dose of purified omega-3 as compared to corn oil did not improve serum concentrations of vitamin D.

Platelet factor-3 activity and availability, platelet phospholipids and their fatty acid and aldehyde composition have been examined in males with non-acute ischemic heart disease and in a control group. Increased platelet factor-3 activity was present in platelet-rich but not in platelet-poor plasma from the patients. No difference in the increase of activity after exposure of PRP to ADP, kaolin or freezing and thawing three times was observed compared with the controls. Estimated per 10° platelets, increased amounts of ethanolamine glycerides, serine phosphoglycerides, choline phosphoglycerides, sphingomyeline and total lipid phosphorus were found in the patient group. The phospholipid: protein ratio was also increased. Only small changes were observed in the fatty acid pattern of the various phospholipids. A slight decrease in palmitic acid and a slight increase in oleic acid were found in most fractions.

The effect of splenectomy in a variety of hematological disorders has been evaluated by a follow-up study of 179 patients 3–15 years after surgery. A lasting remission was obtained in about 75% of patients with idiopathic thrombocytopenic purpura. All patients with hereditary spherocytosis had a complete remission, whereas hereditary non-spherocytic hemolytic anemia was not influenced by splenectomy. More than 50% of patients with acquired hemolytic anemia showed no symptoms of hemolytic disease when examined ten years after surgery. Twenty-five % of the patients with pancytopenia were in good condition ten years after splenectomy. Normal or increased bone marrow cellularity in this condition strengthens the indication for surgery. The proliferative diseases including chronic lymphatic leukemia, lymphosarcoma and myelofibrosis may represent indications for surgery whereas chronic myelogenous leukemia seemed to be a contraindication for splenectomy. The hematological disturbances associated with congestive splenomegaly usually can be corrected by splenectomy.

30 healthy male subjects were given an isocaloric meal composed mainly of saturated or unsaturated fat. Before and 2 h after the completion of the meal plasma and platelet lipids, platelet factor 3 and platelet factor 4 activity were examined. During alimentary hyperlipaemia a significant increase of platelet triglycerides was seen after both meals. The platelet triglycerides reflected the dietary fatty acids. After the saturated fatty meal an increase of platelet factor 4 activity was present in platelet poor plasma and a decrease in platelet factor 3 availability was present. In 5 subjects with primary hyperlipoproteinaemia all characterized by high levels of plasma triglycerides, the platelet triglycerides and the platelet factor 3 activity and availability were similar to what was found in normal fasting subjects.

Two subgroups of healthy males from an inland and a coastal community in Norway with a traditionally low and high consumption of dietary fish were given a dietary supplement of 20 ml cod liver oil rich in n-3 polyunsaturated fatty acids for 3 weeks. Cod liver oil induced an increase in serum high density lipoprotein (HDL) cholesterol in men from the inland. Both groups showed a prolonged primary bleeding time, whereas platelet aggregation and thromboxane A2 production induced by collagen were mainly unaffected. Platelet phospholipid fatty acids showed similar changes in both groups with a decrease in n-6 and an increase in n-3 polyunsaturated fatty acids. No changes were observed in total cholesterol or platelet phospholipid content. This study shows that dietary supplement with cod liver oil induces changes in serum lipids and platelets that may reduce the tendency to thrombosis both in subjects with a low and in those with a high intake of dietary fish. The effects were more pronounced in the subjects with a traditionally low fish consumption.

The concentration of total cholesterol, total phospholipids, triglycerides (TG) and free fatty acids (FFA) in plasma and platelets has been evaluated in 11 healthy male subjects. The distribution of the different fatty acids in FFA and TG from the two compartments was measured. All subjects had plasma lipid concentrations within the normal limits. No significant correlation could be established between the concentrations of any of the main lipid fractions in plasma and platelets. A highly significant correlation was found between FFA stearic acid in plasma and platelets, and a correlation was also established for palmitoleic and oleic acids, whereas a non-significant correlation was found for FFA palmitic acid. No correlation could be established for FFA polyunsaturated fatty acids or for triglyceride fatty acids.

Platelet factor-3 activity and availability, platelet phospholipids, their fatty acid and aldehyde composition and plasma lipids have been examined in patients with hyperbetalipoproteinemia before and after treatment with nicotinic acid or clofibrate. Increased platelet factor-3 activity was present in platelet-rich plasma, and increased availability was found after exposure of platelets to adenosine diphosphate. Estimated per 109 platelets, increased amounts of platelet phospholipids were found in the patients, whereas the phospholipid fatty acid pattern was as in normals. After treatment with nicotinic acid and also clofibrate, the platelet factor-3 activity and availability were normalized. No changes were observed in platelet factor-3 activity in platelet-poor plasma or in the quantity of platelet phospholipids and their fatty acids during the treatment. Plasma cholesterol and phospholipids were markedly decreased by the treatment. It is suggested that an interaction exists between platelets and plasma lipoproteins. In patients with hyperbetalipoproteinemia this interaction may favour the tendency to thrombosis and can be reversed by treatment with nicotinic acid and probably clofibrate.

Coronary heart disease (CHD) mortality was registered in an inland and a coastal community in Northern Norway. Subgroups of healthy males from the communities were investigated further. The daily consumption of fish in the coastal and inland areas was 132.4 g and 55.1 g respectively, and the intake of eicosapentaenoic acid was 0.9 g and 0.25 g. The content of n-3 polyunsaturated fatty acids in platelet phospholipids and primary bleeding time were similar in the two groups. Linoleic acid was lower and saturated fatty acids were higher in phospholipids in men from the coastal area. Collagen-induced platelet aggregation was increased and serum triglyceride concentration was higher in men from the coastal area. CHD mortality during a 10-year period was higher in the coastal area for both sexes. This may be associated with differences in serum triglyceride levels and platelet fatty acid composition. This study indicates that a high consumption of lean fish is not sufficient to induce changes in blood lipids and platelet function associated with low CHD mortality and it does not seem to prevent high CHD mortality.

Two groups, each of 10 subjects, have been given isocaloric diets for 21 days. The diets were identical with the exception of their fat content. One group was given 40% of the calories as soybean oil, and the other the same amount as MCT oil. Platelet and serum lipids and platelet function tests were evaluated before and after the dietary period. The platelet lipid analysis included estimation of total cholesterol and phospholipids, fractionation of phospholipids by thin layer chromatography and gas liquid chromatographic estimation of the fatty acid and aldehyde composition of the various phospholipids. Platelet function tests included platelet factor-3 (PF-3) activity and availability, platelet aggregation induced by collagen, ADP and thrombin and platelet electrophoresis. In subjects given a soybean oil diet a significant reduction in serum total cholesterol and phospholipids occurred. No changes were observed in the platelet cholesterol and phospholipid levels, whereas a significant increase of linoleic acid in choline, ethanolamine and serine phosphoglycerides took place. The relative increase of linoleic acid was most marked in the choline phosphoglycerides. A moderate decrease in palmitic and oleic acids was seen in most phospholipid fractions. PF-3 activity in platelet-rich plasma showed a consistent decrease in these subjects, whereas the other platelet function tests showed insignificant changes. In subjects given MCT oil diet no significant changes were observed in serum or platelet lipids, including the phospholipid fatty acids. Increased PF-3 activity in platelet-rich plasma exposed to ADP was the only functional disturbance observed in this group.

Background and aim A family history of myocardial infarction (MI) is an independent risk factor for future coronary events. Decreased plasma lipoprotein lipase (LPL) activity is associated with delayed clearance of triglyceride-rich lipoproteins (TRL) and low fasting HDL cholesterol. The aim of the study was to investigate the relations between plasma LPL activity, postprandial TRL and HDL cholesterol in offspring of MI patients. Methods and results A case-control study was performed in 17 healthy middle-aged offspring of MI patients and 13 healthy age-and sex-matched controls. Fasting blood samples were collected and each subject was given a standardized oral fat load (1 g fat/kg body weight) with subsequent blood samples collected for an 8-h period. Offspring of MI patients had significantly lower postheparin LPL activity (62.9 mU/ml ± 22.8 mU/ml) (mean ± SD) than healthy controls (93.0 mU/ml ± 21.7 mU/ml) ( p = 0.002). Decreased postheparin LPL activity was accompanied by significantly increased and delayed clearance of postprandial TRL and subsequent lower fasting HDL cholesterol in offspring of MI patients. Postheparin LPL activity was associated with HDL cholesterol ( r = 0.40, p = 0.036) and trend analysis revealed a decrease in incremental area under the curve (AUCi) for chylomicrons with increasing LPL activity ( p = 0.013). Conclusions Offspring of MI patients had decreased postheparin LPL activity accompanied by increased postprandial TRL and subsequent decreased HDL cholesterol, an unfavourable lipid profile which may contribute to their increased risk for future coronary events.

SummaryFormation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-FVIIa complexes on ruptured atherosclerotic plaques is thought to be a key event in acute MI. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation by neutralizing FXa and inhibiting the TF-FVIIa complex. A case control study was conducted to investigate the role of coagulation activation in MI. Sixty-two patients with verified MI, 40-60 yrs of age, were recruited into the study and examined 1-4 years after the acute coronary event. Thrombinantithrombin complex (TAT) was significantly increased in MI patients (8.2 ± 12.9 µg/l vs. 3.9 ± 2.6 µg/l, p=0.01). In contrast, FVIIa was lower in MI patients (41 ± 13 mU/ml vs. 48 ± 15 mU/ml, p=0.003) accompanied by an increase in plasma free TFPI antigen (20.9 ± 5.0 ng/ml vs. 19.2 ± 4.9 ng/ml, p=0.03). Significant trends for increase in triglycerides and total cholesterol across quartiles of free TFPI Ag were found in both groups, whereas HDL cholesterol decreased across quartiles of TFPI among control subjects. The compensatory increase in plasma free TFPI with established lipid and haemostatic risk factors were abrogated in the MI patients. An apparent increase in the basal activation of the coagulation system was observed in young patients with MI. Enhanced coagulation activation was accompanied by a decrease in FVIIa and increase in free TFPI Ag, probably reflecting a modest triggering of TF-induced coagulation in these patients.

To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins combined with n-3 PUFAs or corn oil.A prospective, randomised, double-blind, controlled study.One hospital centre in Stavanger, Norway.A total of 300 subjects with an acute myocardial infarction (MI).Gelatine capsules, containing 850-882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation.After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA-MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA-MDA at 12 months follow-up, P=0.004. We found no impact of statins on TBA-MDA.TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment.: Pharmacia A/S and Pronova A/S, Norway.

Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes. Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postprandial hyperlipemia. In the present double-blind, placebo-controlled parallel study, 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L(-1 )and serum cholesterol >5.3 mmol L-1 at the end of a 3-month dietary run-in period were treated with atorvastatin at 10 mg day-1 for at least 10 weeks. During the last 5 weeks the patients were randomized into two groups receiving 1.68 g day(-1) omega-3 fatty acids (omega-3 FA) or placebo (corn oil). The fasting levels of FVII antigen (FVII-Ag) and FVII coagulant activity (FVII:C) were high compared with healthy males. The fasting levels of activated FVII (FVIIa) and FVII-Ag correlated both to serum triglycerides and apolipoprotein A1 (apoA1). FVIIa and FVII:C increased during postprandial hyperlipemia. This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels, but not to the degree of postprandial hypertriglyceridemia. The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo. This treatment also reduced the postprandial level of FVIIa. omega-3 FA in addition to atorvastatin further reduced FVIIa concentrations, fasting and postprandially, and also significantly reduced FVII:C and FVII-Ag during postprandial hyperlipemia. Prothrombin fragment 1 + 2 (F1 + 2) increased during postprandial hyperlipemia. This increase was significantly reduced after treatment with atorvastatin plus omega-3 FA. The increase of F1 + 2 measured as incremental area under the curve (iAUC) during postprandial hyperlipemia correlated to the fasting levels of FVIIa, FVII:C and FVII-Ag and also to the levels of these factors during postprandial lipemia. In conclusion, patients with combined hyperlipemia are at risk for activation of the coagulation system, particularly during postprandial lipemia. This activation may be significantly reduced by statins and omega-3 FA.

Fourteen healthy male volunteers were given two separate high-saturated-fat meals with and without the addition of 4 g highly purified ethyl esters of either eicosapentaenoic acid (EPA) (95% pure, n = 7) or docosahexaenoic acid (DHA) (90% pure, n = 7) supplied as 1-g capsules each containing 3.4 mg vitamin E. The chylomicrons were isolated 6 h after the meals, at peak concentrations of n-3 fatty acids (FA). Addition of n-3 FA with the meal caused a 10.4-fold increase in the concentration of n-3 FA in chylomicrons compared to the saturated fat meal without addition of n-3 FA. After the saturated-fat meal, the concentration of thiobarbituric acid-reactive substances (TBARS) was 327.6 +/- 34.6 nmol/mmol triacylglycerol (TAG), which increased to 1015.8 +/- 212.0 nmol/mmol TAG (P0.0001, n = 14) after EPA and DHA were added to the meal. There was no significant correlation between the concentrations of TBARS and vitamin E in the chylomicrons collected 6 h after the test meal. The present findings demonstrate an immediate increase in chylomicron peroxidation ex vivo provided by intake of highly purified n-3 FA. The capsular content of vitamin E was absorbed into chylomicrons, but the amount of vitamin E was apparently not sufficient to protect chylomicrons against lipid peroxidation ex vivo. Daily intake of 4 g n-3 FA either as EPA or DHA for 5 wk did not change the plasma concentration of TBARS. Although not significantly different between groups, DHA supplementation decreased total glutathione in plasma (P0.05) and EPA supplementation increased plasma concentration of vitamin E (P0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n-3 FA.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation, which is increased several-fold in post-heparin plasma and thought to contribute significantly to the antithrombotic action of heparin. In the present study we investigated whether subcutaneous (s.c.) administration of a low molecular weight heparin (LMWH), enoxaparin, had a different effect on intravascular pools of TFPI compared with continuous i.v. infusion of unfractionated heparin (UFH). 18 healthy male volunteers were randomly assigned to continuous i.v. infusion with UFH (initially 450 U/kg/24 h, n = 6) or to s.c. treatment with LMWH once daily (enoxaparin, 1.5 mg/kg, n = 12) for 72 h. A bolus injection of 5000 IU UFH i.v. caused an 8–13-fold increase in plasma-free TFPI antigen (TFPI Ag), followed by a progressive decrease (81 ± 4%, P

Fourteen healthy volunteers were randomly allocated to receive 4 g highly purified ethyl esters of eicosapentaenoic acid (EPA) (95% pure, n = 7) or docosahexaenoic acid (DHA) (90% pure, n = 7) daily for 5 wk in supplement to their ordinary diet. The n-3 fatty acids were given with a standard high-fat meal at the beginning and the end of the supplementation period. EPA and DHA induced a similar incorporation into chylomicrons which peaked 6 h after the meal. The relative uptake of EPA and DHA from the meal was90% compared with the uptake of oleic acid. During absorption, there was no significant elongation or retroconversion of EPA or DHA in total chylomicron fatty acids. The concentration of EPA decreased by 13% and DHA by 62% (P0.001) between 6 and 8 h after the meal. During the 5-wk supplementation period, EPA showed a more rapid and comprehensive increase in serum phospholipids than did DHA. DHA was retroconverted to EPA, whereas EPA was elongated to docosapentaenoic acid (DPA). The postprandial triglyceridemia was suppressed by 19 and 49% after prolonged intake of EPA and DHA, respectively, indicating that prolonged intake of DHA is equivalent to or even more efficient than that of EPA in lowering postprandial triglyceridemia. This study indicates that there are metabolic differences between EPA and DHA which may have implications for the use of n-3 fatty acids in preventive and clinical medicine.

Abstract Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (ω3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of ω3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII c , and platelet count were measured before and after intervention (mean±SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8±1.0 U/mL versus 3.5±1.2 U/mL, P =.25), as did tPA (−0.02±0.02 IU/mL versus −0.13±0.03 IU/mL, P =.28), levels of factor VII c (6±5% versus 5±4%, P >.3), and platelet count (2±7×10 9 /L versus 3±5×10 9 /L, P >.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6±0.1 g/L, P =.0001) and corn oil (0.4±0.1 g/L, P =.002) intake. There was no between-group difference ( P >.3). In conclusion, a daily intake of 4 g ω3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic coagulation system. In human plasma 70–85% is associated with apoB-containing lipoproteins whereas 10–20% exists in a carrier free form. The purpose of the present study was to assess the anticoagulant function of TFPI in complex with low density lipoproteins (LDL) on tissue factor (TF)-induced coagulation in vitro. LDL-TFPI complexes were isolated by preparative density gradient ultracentrifugation, LDL-free TFPI by preparative gel filtration and the anticoagulant properties were assessed by a diluted prothrombin time assay (dPT). LDL-free TFPI (0–0.46 U/ml) added to the dPT mixture, caused a prominent dose-dependent prolongation of dPT (0–42.2 sec.) which could be abolished by the addition of blocking anti-TFPI IgG. Contrary, increasing amounts of LDL-bound TFPI (0–4.0 U/ml) shortened dPT by 11.4 sec at the highest concentration. LDL-bound TFPI was not immunodetected by anti-TFPI IgG directed against the distal portion of the C-terminus, and appeared on Western blotting with a major band at 67 kDa and a weak band at 34 kDa which suggest that LDL-bound TFPI lack anticoagulant function due to carboxy terminal truncation. Our data provide evidence for the hypothesis that the anticoagulant function of TFPI is restricted to its carrier free form in human plasma. © 1997 Elsevier Science Ltd

SummaryTissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic coagulation system. TFPI is increased several-fold in postheparin plasma and thereby thought to contribute significantly to the antithrombotic action of heparin. The present study was conducted to investigate how repeated (n = 8) and continuous (n = 6) administration of heparin affect plasma TFPI and the inhibition of tissue factor (TF)-induced coagulation ex vivo in humans. Free TFPI antigen (TFPI Ag) increased from 19.2 ± 4.0 ng/ml to 204.7 ± 31.7 ng/ml after intravenous injection of 5000IU of unfractionated heparin. Five repeated injections of 5000 IU of heparin at 4 h intervals caused a progressive decrease (−45 ± 8%, p

The protective effect of endogenous sex hormones is commonly believed to explain the gender gap in the risk of coronary heart disease and the diminished protection in women when menopause occurs. Recent reports indicate that iron overload, due to cessation of menstrual bleeding, may be an important factor. We therefore investigated iron stores by serum ferritin measurements in healthy premenopausal (n = 113) and postmenopausal (n = 46) women. Ferritin levels were higher in postmenopausal than in premenopausal women, both in blood donors (43.4 versus 23.1 micrograms/L, P < .001) and in nondonors (71.7 versus 32.8 micrograms/L, P < .001). Serum ferritin was positively correlated with age (r = .36, P < .001). After age adjustment, serum ferritin was positively correlated with hemoglobin, hematocrit, serum total cholesterol, and low-density lipoprotein (LDL) cholesterol. Total cholesterol was correlated with age (r = .66, P < .001), as were LDL cholesterol (r = .60, P < .01) and high-density lipoprotein cholesterol (r = .32, P < .01). Neither ferritin nor serum lipids were directly associated with female sex hormone levels. The mutual relation between ferritin, hemoglobin, and hematocrit probably only indicates their usefulness as measures of body iron. The parallel rise in serum ferritin, total cholesterol, and LDL cholesterol might contribute to the increased risk of coronary heart disease among postmenopausal women.

Fourteen patients suffering from familial hypercholesterolemia (type IIa) participated in a double-blind, placebo-controlled trial that evaluated the effects of fish oil ethyl ester (K-85, 5.7 g/day) or a hydroxymethylglutaryl coenzyme A reductase inhibitor (lovastatin, 40 mg/day) alone or in combination on lipid metabolism and bleeding time at rest and after standardized exercise. Lovastatin treatment reduced total cholesterol (-27%), low density lipoprotein cholesterol (-37%), and triglycerides (-18%), whereas high density lipoprotein cholesterol increased significantly (14%). K-85 affected total (-4%), low density lipoprotein (-9%), and high density lipoprotein (+7%) cholesterol insignificantly, whereas the triglyceride level decreased by 24% (p < 0.001). The combined regimen caused an additive decrease in the triglyceride level (41%), which differed significantly (p < 0.01) from that gained by lovastatin alone. Under basal conditions the bleeding time was not influenced by the different interventions. Standardized exercise shortened the bleeding time by 19% (p < 0.001) and 16% (p < 0.001) before intervention and after lovastatin treatment, respectively. After K-85 alone or in combination with lovastatin, the exercise-induced shortening of the bleeding time was totally inhibited, which may reflect a favorable influence of fish oil on the platelet-vessel wall interaction in these high-risk patients.

A sex difference in the bleeding time has been reported. To investigate the effects of the different sex hormones, the bleeding time (BT) and hemostatic factors related to it were measured in 209 healthy women: 50 pregnant, 113 menstruating and 46 post-menopausal. The serum levels of estrogens, progesterone and testosterone were distributed as expected for the different groups. There were no significant differences in the BT between any of the groups. No correlations between the BT and female or male sex hormones were found. The findings indicate that although sex hormone mediated effects on platelet/endothelial cell interactions may exist, they do not become evident within the physiological variations in the BT of healthy women.

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.

The present study reports on the effects of myristic(14:0), palmitic(16:0) and stearic(18:0) acids separately and combined with linoleic(18:2n-6), arachidonic(20:4n-6) and eicosapentaenoic(20:5n-3) acids on cultured human endothelial cell monolayers(ECM). The cell viability determined by trypan blue exclusion study, the release of lactate dehydrogenase(LDH) and 6-keto-PGF1 alpha into the medium from ECM incubated with albumin bound fatty acids(FA) were measured. The cell viability was reduced and the release of LDH from ECM was enhanced by 18:0(0.2mM, ratio 1, 2 and 4) and 16:0(0.4mM, ratio 2), but not by 14:0, or the unsaturated FA. The reduced cell viability induced by 18:0 was completely inhibited by polyunsaturated FA, 18:2n-6, 20:4n-6 and 20:5n-3. The release of 6-keto-PGF1 alpha was increased by 18:0, but not by 14:0 and 16:0. All three saturated FA potentiated 6-keto-PGF1 alpha production induced by 20:4n-6. Combined with 18:2n-6 or 20:5n-3, they also stimulated 6-keto-PGF1 alpha production. This study indicates that the three main dietary SFA, 18:0, 16:0 and 14:0 do not have the same effects on ECM. The damaging effect on endothelial cells induced by 18:0 and 16:0 may be of significance for the thrombogenic effects related to these saturated fatty acids.

Tissue factor (TF)-induced thrombin generation (TG) ex vivo has been suggested to be an important method to assess thrombotic risk. No studies have investigated the impact of postprandial lipemia on TF-induced TG. Since myocardial infarction (MI) is associated with elevated postprandial levels of triglycerides, we hypothesized a differential impact of postprandial lipemia on coagulation activation in MI-patients and healthy controls.Elderly survivors of acute MI (n=44) and healthy age-and sex matched controls (n=43) underwent a fat tolerance test (1 gram per kg body weight) to assess coagulation activation during postprandial lipemia.The incremental area under the curve (AUCi) for serum triglycerides was higher in MI-patients than in healthy age-and sex matched controls (5.64±0.52 mmol/L*h and 3.94±0.39 mmol/L*h, p=0.012) during the postprandial phase. Subsequent endogenous activation of coagulation, assessed by FVIIa and thrombin generation (F1+2), was similar among groups and not related to levels of triglycerides during the postprandial phase. Healthy individuals had a gradual decline in TF-induced thrombin generation ex vivo, assessed by endogenous thrombin potential (ETP) (AUCi=-542.4±71.4 nM*min*h, p0.001), whereas MI-patients retained their ETP (AUCi=127.4±89.0 nM*min*h, p=0.47) in plasma during the postprandial phase (p for group difference=0.005).MI-patients had elevated postprandial lipemia and retained their ability for TF-induced TG in plasma ex vivo in the postprandial phase, whereas the capacity gradually decreased in healthy individuals. Further studies are warranted to reveal underlying mechanism(s) and clinical implications.

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

Postprandial triglyceride-rich lipoproteins (TRL) levels are a predictor for coronary atherosclerosis. The aim of the study was to compare fasting high density lipoprotein (HDL) cholesterol, plasma lipoprotein lipase (LPL) activity, and postprandial TRL between elderly survivors of myocardial infarction (MI) and healthy controls. A case-control study was performed in 44 elderly patients 65-85 years of age with a previous history of MI and 43 age- and sex-matched healthy controls. Each participant underwent physical examination and was given a standard oral fat load with subsequent blood sampling over the next 8 h. Total and chylomicron triglycerides were assessed by area under the curve (AUC), incremental are under the curve (AUCi) and triglyceride response (TGR). Elderly MI patients had significantly lower postheparin LPL activity (87.4 +/- 36.9 mU/ml) (mean +/- 1 SD) than healthy controls (106.0 +/- 29.0 mU/ml) (P = 0.014). Decreased postheparin LPL activity was accompanied by significant increased and delayed clearance of postprandial TRL. Fasting HDL cholesterol was significantly lower in elderly MI patients than controls (1.45 +/- 0.32 and 1.66 +/- 0.47 mmol/l, respectively, P = 0.048). Multiple regression analysis revealed postheparin LPL activity as an independent predictor for postprandial TRL and fasting HDL cholesterol. Logistic regressions analysis revealed HDL cholesterol, triglycerides measured 2 h after the oral fat load, and postheparin LPL activity as independent predictors for MI. Our findings indicate that decreased fasting HDL cholesterol is associated with increased postprandial triglyceridemia which could be a target for life-style and therapeutic interventions in patients at risk for cardiovascular disease.

Tissue-factor-pathway inhibitor is the principal regulator of tissue factor-induced coagulation. Heparin treatment mobilizes TFPI into the circulation and contributes to the anticoagulant effects of heparins. Previous studies have demonstrated a selective depletion of intravascular TFPI by unfractionated heparin (UFH) but not by low-molecular-weight heparin (LMWH). In this study we sought to investigate the time- and dose-dependent relationships between release of TFPI and lipoprotein lipase (LPL) in respons to UFH and LMWH and to investigate whether the selective depletion of TFPI by UFH but not by LMWH is related to differential urinary excretion of TFPI. Eight healthy males participated in an open crossover study in which participants were assigned to receive (1) continuous infusion of unfractionated heparin (UFH, 450 IU/kg/24 hr); (2) subcutaneous dalteparin, 100 IU/kg given twice at a 12-hr interval; (3) subcutaneous dalteparin, 200 IU/kg given once; or (4) saline-solution infusion. Similar dose-dependent mobilization of TFPI and lipoprotein lipase (LPL), another glucosaminoglycan (GAG)-anchored protein of the endothelial membrane, was observed after both subcutaneous and intravenous administration of heparins. However, UFH induced a more efficient release of both TFPI and LPL into plasma than did LMWH at equivalent anti-Xa levels, indicating molecular-weight dependence of the release reactions. However, LPL reached peak levels faster and was more rapidly cleared from the circulation than was TFPI, regardless of the treatment modality. Only trace amounts of TFPI were detected in the urine in a native form (38 kD). UFH and LMWH treatment reduced renal clearance of TFPI compared with the control regimen. Our findings suggest that displacement of TFPI from the endothelial-surface GAG is the main mechanism for TFPI release during heparin treatment in vivo and that differential urinary excretion of TFPI is not the explanation for selective depletion of TFPI during UFH treatment.

We hypothesized that n–3 polyunsaturated fatty acids (n–3 PUFAs) as compared to corn oil administered for 1 year following an acute myocardial infarction (MI) may reduce plasma total homocysteine (p-tHcy), ultrasensitive C-reactive protein (µCRP), and the adhesive properties of the endothelium, expressed as soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1). In a prospective, randomised, double-blind study, 300 acute MI patients were allocated to highly concentrated n–3 PUFAs (n = 150) or corn oil (n = 150). After 1 year on treatment there was an intergroup difference in p-tHcy in favour of the n–3 group (n = 118), p = 0.022. However, sE-selectin, sICAM-1 and µCRP were unaffected by the treatment. In conclusion, reduction of p-tHcy by long-term n–3 PUFAs treatment was not associated with demonstrable effects on markers of endothelial adhesion properties.

Impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for atherothrombotic disease. Many studies have reported a positive correlation between serum triglycerides and PAI-1 activity. Dietary intervention with very long n-3 fatty acids from marine sources is known to decrease serum triglycerides, but an adverse increase in PAI-1 activity has been reported in some studies. A double blind, placebo controlled study was conducted among 224 middle-aged (ages 36–56), healthy, non-smoking men in which the participants were randomly assigned to daily supplementation with 3.8 g eicosapentaenoic acid/d, 3.6 g docosahexaenoic acid/d, or 4.0 g corn oil/d (placebo) for 7 weeks. PAI-1 activity increased by 2.35±6.24 U/ml (28%), 1.15±6.74 U/ml (14%), and 1.33±5.64 U/ml (22%) during dietary supplementation with eicosapentaenoic acid, docosahexaenoic acid, and corn oil, respectively, but the changes were not significantly different between groups p=0.43 . There was no relationship between change in concentrations of serum triglycerides or phospholipid n-3 fatty acids and change in PAI-1 activity. At baseline, analysis was performed to investigate the influence of dietary lipids, blood lipids, and serum fatty acids on plasma concentrations of PAI-1 activity. Dietary intake of saturated fat correlated directly with PAI-1 both in crude analysis r=0,14, p and after adjustment for age and body mass index (kg/m2) r=0.20, p . Furthermore, PAI-1 was associated with body mass index r=0.32, p , apo-B100 r=0.27, p , serum triglycerides r=0.31, p , and the concentration of n-6 polyunsaturated fatty acids r=0.22, p in serum. In a multiple regression analysis, 21% of the variation in PAI-1 activity could be explained by these variables. Plasma PAI-1 activity did not correlate with dietary intake or serum concentrations of n-3 polyunsaturated fatty acids. In a review of 17 trials, including 935 subjects that assessed the effect of n-3 fatty acids on PAI-1 activity, an overall 17.7% increase in PAI-1 activity was estimated by n-3 supplementation. However, only two studies were able to demonstrate a significant increase in PAI-1 attributable to n-3 fatty acid supplementation. We conclude that there is no strong evidence for an unfavourable, clinically relevant effect of n-3 fatty acids on PAI-1 activity in plasma.

Abstract —Patients with combined hyperlipemia have lipid abnormalities associated with an increased tendency to develop atherosclerosis and thrombosis. This tendency may be accelerated during postprandial hyperlipemia. In the present double-blind parallel study, 41 patients with combined hyperlipemia and serum triacylglycerols between 2.0 and 15.0 mmol/L and serum total cholesterol >5.3 mmol/L at the end of a 3-month dietary run-in period were treated with simvastatin at 20 mg/d for at least 10 weeks; patients were then randomized into 2 groups receiving simvastatin+ω-3 fatty acids at 3.36 g/d or placebo (corn oil) for an additional 5 weeks. Hemostatic variables that have been associated with increased thrombotic tendency were evaluated with subjects in the fasting state and during postprandial hyperlipemia before and after combined treatment. Supplementation of ω-3 fatty acid reduced tissue factor pathway inhibitor antigen ( P P

The n-3 fatty acids (FA) from marine sources are known to exert antiinflammatory effects on monocyte function. There is still controversy whether n-3 FA may increase the susceptibility to infections. The present study was designed to assess the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on monocyte phagocytosis and respiratory burst activity. Fifty-eight healthy men were randomized to take a daily supplement of 3.8 g highly purified EPA (n = 20), 3.6 g DHA (n = 19), or corn oil (n = 19) for 7 wk. Mononuclear leukocytes were collected, isolated, and cryopreserved prior to and after dietary supplementation. Paired samples were analyzed in the presence of autologous serum in a crossover design. Monocyte phagocytosis and respiratory burst activity were measured by flow cytometry after ingestion of Escherichia coli. Monocytes retained their phagocytic ability and respiratory burst activity after supplementation. No reduction in internalization of bacteria was registered. Dietary n-3 FA and particularly EPA improved bacterial adherence to the monocyte surface. In the crossover experiments, there was an adverse effect of serum enriched with n-3 FA on bacterial adherence. We conclude that monocytes retain their phagocytic potential after supplementation with purified EPA and DHA.

To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on serum lipids, apolipoproteins, and serum phospholipid fatty acids in humans, we conducted a double-blind, placebo-controlled, parallel design intervention study. Healthy nonsmoking men (n = 234) aged 36-56 y were randomly assigned to dietary supplementation with 3.8 g EPA/d, 3.6 g DHA/d, or 4.0 g corn oil/d (placebo) for 7 wk. Serum triacylglycerols decreased 26% (P < 0.0001) in the DHA group and 21% (P = 0.0001) in the EPA group compared with the corn oil group. Although not significant, net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations. Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L (P = 0.0002) in the DHA group. In the EPA group, serum total cholesterol decreased 0.15 mmol/L (P = 0.02) and apolipoprotein A-I decreased 0.04 g/L (P = 0.0003). In the DHA group, serum phospholipid DHA increased by 69% and EPA increased by 29%, indicating retroconversion of DHA to EPA. In the EPA group, serum phospholipid EPA increased by 297% whereas DHA decreased by 15%, suggesting that EPA is not elongated to DHA in humans. The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups, whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group. We conclude that both DHA and EPA decrease serum triacylglycerols, but have differential effects on lipoprotein and fatty acid metabolism in humans.

Abstract Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose ( r =.41, P =.002), insulin sensitivity ( r =−.35, P =.01), and insulin-induced suppression of nonesterified fatty acid (NEFA) ( r =−.43, P =.007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index ( r =.62, P =.0005), waist-to-hip ratio ( r =.75, P =.0001), plasma glucose ( r =.50, P =.007), insulin ( r =.49, P =.009), proinsulin ( r =.57, P =.002), C-peptide ( r =.60, P =.0009), insulin sensitivity ( r =−.74, P =.0001), NEFA suppression ( r =−.64, P =.003), and triglycerides ( r =.58, P =.001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.

Abstract Tissue factor pathway inhibitor (TFPI) inhibits the extrinsic coagulation system. A major pool of TFPI is associated with the vascular endothelium and can be mobilized into the circulation by heparin. In circulating blood, TFPI is mainly associated with LDL (80%), whereas 10% to 20% is carrier free. In this study, heparin administration caused a 2.2-fold and a 7.5-fold increase in TFPI activity and TFPI antigen, respectively, in 25 patients with phenotypes IIa and IIb hyperbetalipoproteinemia. Because the antigen determination of TFPI almost exclusively measures carrier-free TFPI, more than 90% of the heparin-induced increase in TFPI activity was caused by mobilization of carrier-free TFPI from the vascular endothelium. Therapeutic lowering of total cholesterol (a decrease of 31.1±11.6%, P P

Epidemiological studies have provided evidence that attenuated fibrinolytic activity and increased antigen levels of plasminogen activator are risk factors for coronary heart disease (CHD). In a comparative study, tissue plasminogen activator (t-PA) antigen and activity concentrations were examined in plasma from familial hypercholesterolaemia (FH) patients without manifest CHD (n = 14) and in age- and sex-matched normolipaemic controls (NLC) at rest and after the same bicycle exercise. The FH patients had higher systolic and diastolic blood pressure than their controls. The plasma level of t-PA antigen was higher in FH patients than in NLC under basal conditions (7.3 +/- 3.1 ng/ml vs 4.8 +/- 2.2 ng/ml, P = 0.022), whereas no difference was found in t-PA activity. Bicycle exercise induced a marked increase in t-PA antigen (P < 0.001 for both groups) which did not differ between groups. A more prominent rise in t-PA activity was observed among the FH patients during the exercise (1.71 +/- 0.99 vs 0.85 +/- 0.89 IU/ml, P = 0.24). Neither the basal level of thrombin-antithrombin III complex (TAT) nor the significant increase (P < 0.001 for both groups) induced by exercise differed between groups. A high t-PA antigen level may precede clinical manifestations of cardiovascular disease in patients with familial hypercholesterolaemia.

Tissue-factor pathway inhibitor (TFPI) is a potent inhibitor of extrinsic coagulation, which is mainly associated with lipoproteins in circulating blood. Gel filtration of human plasma confirmed the presence of three peaks in which approximately 10%, 70%, and 20% of total TFPI activity was retained. Precipitation of very-low-density lipoproteins and low-density lipoproteins (LDLs) in plasma by polyethylene glycol almost completely abolished peaks and I and II. LDL isolated by ultracentrifugation revealed two peaks of TFPI after gel filtration that coeluted with peaks I and II, respectively, from gel filtration of total plasma. TFPI activity in peaks I and II was also precipitated by anti-apolipoprotein B antibodies. Fourteen patients with familial hypercholesterolemia had higher plasma TFPI activity than did age- and sex-matched normolipemic control subjects (1.45 +/- 0.27 U/mL versus 0.80 +/- 0.09 U/mL, P < .001). Plasma TFPI was correlated with LDL cholesterol (r = .73, P < .001) and apolipoprotein B (r = .69, P < .001). No association was found with high-density lipoprotein cholesterol or apolipoprotein A-I. In a double-blind, placebo-controlled trial among the familial hypercholesterolemia patients, lovastatin alone or in combination with fish oil concentrate lowered plasma TFPI in parallel with LDL cholesterol. Gel filtration of plasma from these patients demonstrated a specific drop in apolipoprotein B-TFPI complexes, whereas TFPI not associated with lipoproteins was unchanged. This study demonstrated that plasma TFPI was associated with and regulated by LDL in plasma from healthy subjects and patients with familial hypercholesterolemia.

The effect of fish oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on serum lipoprotein concentrations is not clear, and it is not known whether EPA and DHA are similarly related to serum lipid or lipoprotein levels. We conducted a randomized, 10-week, dietary supplementation trial in which the effects of 6 g per day of 85% EPA and DHA were compared with 6 g per day of corn oil in 156 men and women. Multivariate analyses were used to assess independent relations between plasma phospholipid EPA and DHA and serum lipoprotein levels. In the fish oil group triglycerides fell 21% (p less than 0.001) and high density lipoprotein cholesterol (HDL-C) rose 3.8% (p less than 0.05). In the corn oil group triglycerides did not change, but HDL-C rose 6.1% (p less than 0.01). Compared with fish oil, apolipoprotein A-I (apo A-I) rose 5.1% after corn oil intake (p less than 0.05). Plasma EPA and DHA levels rose after fish oil intake and fell after corn oil intake (all p less than 0.001). The change (delta) in EPA was inversely correlated with delta triglycerides (p = 0.035) and positively correlated with delta HDL-C and delta apo A-I (both p less than 0.001) in the multivariate analyses. In contrast, delta DHA was not correlated with delta triglycerides but was inversely correlated with delta HDL-C and delta apo A-I (both p less than 0.001). Standardizing for DHA removed the difference in apo A-I levels between groups. This study suggests that EPA and DHA are divergently associated with HDL, possibly through different mechanisms.

double bond at the third position from the methyl end of the molecule (fig. I). The parent fatty acid in this family, a-linolenic acid (l8:3n-3), may be elongated and desaturated to eicosapentaenoic acid (EPA) [20:5n-3] and docosahexaenoic acid (DHA) [22:6n-3], although it is only poorly converted to the more polyunsaturated and desaturated n-3 fatty acids in humans (Bjerve 1989;Dyerberg et al. 1980; Renaud & Nordey 1983). [In the formulae for the fatty acids the first number gives the number of carbon atoms in the fatty acid molecule; the second digit indicates the number of double bonds; n (or omega) indicates the position of the first double 1. n-B Fatty Acids: What are They? Where are They? Do We Need Them? Although experimental studies in animals provided some evidence for an anti thrombotic effect of dietary n-3 fatty acids (Nordey 1965; Nordey et al. 1968), it was the pioneering work of Dyerberg et al. (1975, 1978) in Greenland Eskimos that introduced these fatty acids to clinical medicine, During the last decade it has been reported that the n-3 fatty acids have a wide range of important biological and physiological effects in humans. Despite this, the n-3 fatty acids have not previously been considered an essential nutrient, and only recently have international and national dietary recommendations even included requirements for n3 fatty acids. In 1982, Holman et al. reported alinolenic acid deficiency in a 6-year-old girl who had been treated with a formula diet low in n-3 fatty acids. The girl had visual and cerebral disturbances that disappeared rapidly after supplementation with these fatty acids. More recently, Bjerve (1989) has reported 9 patients with n-3 fatty acid deficiency. All 9 patients had been hospitalised for several years due to severe brain damage which necessitated long term gastric tube feeding. Dietary supply of n-3 fatty acids corrected biochemical deviations and clinical symptoms related to n-3 fatty acid deficiency.

We have frequently found an unacceptable number of hospital records and discharge reports lacking even the most basic information. To improve on this, we reviewed our hospital records and discharge reports on a regular basis, and we sent out questionnaires on quality of care to patients shortly after discharge. The hospital's medical staff received the results as a summarised report every other week. We deliberately disclosed only half of the variables studied. At the end of one year, the results were compared with those obtained before the intervention. Our study took place from September 1994 to October 1995 at the Department of Internal Medicine, University Hospital of Troms⊘ (120 beds and 45 doctors). We reviewed the hospital records for two sets of information: variables that were disclosed to the staff (past or present occupation, smoking habits, general physical condition, and blood pressure) …

The effects of estradiol and progesterone added to the growth medium of human umbilical vein endothelial cells for 72 h on the formation and release of prostacyclin were investigated. The influence on collagen-induced platelet aggregation and on the platelet formation of thromboxane A2 following aggregation, of the growth medium collected before and after thrombin stimulation of the endothelial cells, was studied simultaneously. Under basal conditions, endothelial cells grown with progesterone released significantly less prostacyclin into the growth medium than did controls (p < 0.05). Following thrombin stimulation, endothelial cells grown with estradiol (p < 0.05) or a combination of estradiol and progesterone (p < 0.01) contained significantly less prostacyclin than controls. No significant effects on the platelet aggregation or platelet thromboxane formation could be found. This study indicates a lowering effect of both female sex hormones on the endothelial cell prostacyclin formation and release. This may be of significance for the increased risk of vascular disease in pregnant women and oral contraceptive users, but can hardly explain the consequences of the hormonal loss occurring at the menopause.