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Previous studies have shown that postprandial triglyceride-rich lipoproteins (TRLs) are enriched with apolipoprotein-C-I (apoC-I) in healthy individuals with increased intima-media thickness and in patients with coronary artery disease. The purpose of the present study was to determine apoC-I in TRL in persons with carotid atherosclerosis and its relation to plaque area. A population-based case ( n = 42)-control ( n = 39) study was conducted in persons with carotid atherosclerosis, assessed by B-mode ultrasound, and healthy controls. VLDL (Sf 20–400) was isolated in the fasting state and 4 h after ingestion of a standard fat meal. In the fasting state, persons with carotid atherosclerosis had increased number of apoC-I per VLDL-particle compared to persons without carotid atherosclerosis (8.6 ± 5.4 vs. 6.3 ± 4.2, P = 0.018). Total plaque area increased linearly ( P = 0.017) across tertiles of apoC-I per VLDL-particle. In the postprandial state, a similar increase in the number of apoC-I per VLDL-particle occurred in both cases and controls ( P < 0.001), but no significant difference was observed between groups. The number of apoC-I per VLDL-particle in the fasting state was accompanied by delayed clearance of TRL in the postprandial state, and associated with cholesterol enrichment of the VLDL-particles. Our findings support the concept that the number of apoC-I per VLDL-particle may be of importance for initiation and progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Subjects with echolucent carotid plaques have an increased risk of ischemic cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed chylomicron clearance is a risk factor for atherosclerosis. This study was conducted to determine plasma LPL activity and postprandial metabolism of triglycerides in relation to carotid plaque morphology. Plaque echogenicity was assessed by B-mode ultrasound and analysis of the grey scale median (GSM). Echolucent plaques were defined as GSM ≤ 63 (the median) and echogenic plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without carotid plaques were recruited. Blood samples were collected before and at 2-h interval for 8 h after a standard high fat meal. LPL activity and mass was determined before and after heparin administration. Postheparin LPL activity was decreased in subjects with echolucent plaques compared to subjects with echogenic plaques ( P = 0.06) and to controls ( P = 0.04). Plaque echogenicity increased linearly with increasing levels of postheparin LPL activity ( P = 0.02) and mass ( P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance of chylomicron triglycerides compared to controls ( P = 0.04). Low postheparin LPL activity due to attenuated mobilization of LPL from capillary endothelium may play an important role in the formation of echolucent plaques by modulation of postprandial lipids and subsequent fat accumulation in the arterial wall. [ABSTRACT FROM AUTHOR]

Background: Catheter-directed thrombolysis that removes the thrombus and restores patency of the veins appears to be a safe and effective management of acute deep venous thrombosis (DVT). It has been shown to reduce long-term postthrombotic morbidity and improve the quality of life. Pregnancy and the postpartum period are generally considered as contraindications for thrombolysis. However, catheter-directed thrombolytic therapy of DVT may reduce long-term sequelae in these young patients by restoring the patency of veins. The purpose of this pilot study was to evaluate the efficacy of catheter-directed thrombolysis in treating acute symptomatic postpartum DVT. Methods: Patients enrolled had symptomatic acute DVT (<3 weeks duration) within 42 days of childbirth. Thrombolysis was performed using a recombinant human tissue plasminogen activator, alteplase 5 mg i.v. bolus, followed by an infusion at 0.01 mg/kg/h for the next 20-24 hr. Unfractionated heparin 5000 IU bolus followed by 300 IU/kg/24 hr was infused concomitantly into an arm vein. Fibrinogen and cephotest were obtained every 6 hr and maintained at >1 g/l and between 50 and 70 s, respectively, by adjusting heparin and alteplase infusion. Venography was repeated after 20-24 hr and angioplasty (+/- stenting) was performed if stenosis was present. In case of partial thrombolysis infusion was continued for a maximum of 96 hr. Lysis was considered complete if there was less than 5% residual luminal area narrowing. The treatment was considered successful if there was complete or partial resolution of lower extremity pain and edema, and recanalization of vein with less than 30% residual luminal area narrowing. Following thrombolytic therapy, patients were fitted with graduated compression stockings, and anticoagulated with oral warfarin for 1 year (or lifelong in case of stent implantation). Results: Five women with postpartum DVT (four iliofemoral DVTs, and one renal and ovarian vein thrombosis on the left side) had catheter-directed thrombolysis. The treatment was successful in all four cases of iliofemoral DVT and symptom relief was achieved in all five cases. However, despite partial thrombolysis and restoration of some flow in the patient with renal and ovarian vein thrombosis, the renography performed 1 month later showed absent left kidney function. Conclusion: Where expertise exists, endovascular therapy consisting of catheter-directed thrombolysis with angioplasty and stenting in selected cases could be considered as a primary therapeutic procedure in patients with acute postpartum DVT. [ABSTRACT FROM AUTHOR]

Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous (i.v.) and subcutaneous (s.c.) injections of heparins, and may thus contribute to the antithrombotic effect of heparins. We have recently shown that total TFPI activity, plasma free TFPI antigen, and heparin releasable TFPI were partially depleted during repeated and continuous i.v. infusion of unfractionated heparin (UFH), but not during s.c. treatment with a low molecular weight heparin (LMWH). The difference may be attributed to a different mode of action or the different mode of administration. In the present randomized cross-over study, s.c. administration of therapeutic doses of UFH was compared with s.c. administration of two LMWHs. 12 healthy male volunteers were treated for 3 d with UFH, 250 U/kg twice daily, dalteparin, 200 U/kg once daily, and enoxaparin, 1.5 mg/kg once daily. Six participants were also treated with UFH, 300 U/kg once daily. On day 5 a single dose of either drug was given. Peak levels of total TFPI activity and free TFPI antigen were detected 1 h after injection, whereas maximal prolongation of activated partial thromboplastin time (APTT) and peak levels of anti-factor Xa activity and anti-factor IIa activity were detected after 4 h. On UFH administered twice daily, free TFPI antigen decreased by 44% from baseline level before the first injection on day 1 to pre-injection level on day 5. On UFH administered once daily, basal free TFPI antigen decreased by 50%, 56% and 27% on day 2, 3 and 5 respectively, compared with day 1. Minimal depletion of TFPI was detected during treatment with LMWHs. The study demonstrates the different modes of action of LMWHs and UFH and may help to explain the superior antithrombotic efficacy of LMWHs. [ABSTRACT FROM AUTHOR]

Soluble heparin displaces the cytokine hepatocyte growth factor (HGF) from heparan sulphate proteoglycans on the cell surface and in the extracellular matrix into the circulation. We examined serum HGF elevation after heparin injections, and whether there is a difference between unfractionated heparin (UH) and low molecular weight heparin (LMWH) in their ability to increase serum HGF. 20 healthy individuals were randomized to a single injection of intravenous or subcutaneous UH or LMWH. There was a significant increase in HGF from pretreatment values. This HGF was bioactive. When these preparations were compared on the basis of their serum concentrations (anti-factor Xa activity or molar concentrations), the increase in HGF was greater in individuals receiving UH than LMWH. When UH or LMWH were administered over a 5 d period, the increase in HGF, as well as the difference between treatments to induce HGF, remained stable throughout the treatment. In five patients treated with continuous intravenous heparin infusion HGF was increased throughout the treatment period of 5–7 d. In summary, the rise in bioactive HGF after heparin treatment was stable during continued treatment. UH was more potent in inducing HGF increase than LMWH, both after a single injection and after several days of treatment. [ABSTRACT FROM AUTHOR]

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 F. 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 ( P<0.0001, 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 ( P<0.05) and EPA supplementation increased plasma concentration of vitamin E ( P<0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n−3 FA. [ABSTRACT FROM AUTHOR]

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 < 0.001) during the 72 h infusion with UFH. 4 h after discontinuation of the infusion, basal free TFPI Ag and heparin-releasable TFPI were significantly decreased compared with the concentrations before the infusion (30 ± 9% and 27 ± 7%, respectively). In contrast, LMWH treatment did not reduce either basal or heparin-releasable TFPI Ag. The changes in plasma TFPI Ag by UFH and LMWH were statistically different between groups both in pre- (P < 0.001) and post-heparin (P < 0.0001) plasma. The differential effect of UFH and LMWH on intravascular pools of TFPI may contribute to the understanding of the apparent superior efficacy of LMWHs in the treatment of both arterial and venous thrombosis. [ABSTRACT FROM AUTHOR]

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 was >90% 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% ( P<0.001) 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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]