Effect of ω-3 Fatty Acids and Simvastatin on Hemostatic Risk Factors and Postprandial Hyperlipemia in Patients With Combined Hyperlipemia

Abstract

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 Ͼ5.3 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 simvastatinϩ-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 -3 fatty acid reduced tissue factor pathway inhibitor antigen (PϽ0.05) in the fasting state, reduced the degree of postprandial hyperlipemia (PϽ0.005), and reduced activated factor VII concentration appearing during postprandial hyperlipemia. In conclusion, -3 fatty acids given in addition to simvastatin to patients with combined hyperlipemia reduced the free tissue factor pathway inhibitor fraction in the fasting state and inhibited the activation of factor VII occurring during postprandial lipemia, thus representing a potential beneficial effect on the hemostatic risk profile in this patient group. Key Words: combined hyperlipemia Ⅲ postprandial hyperlipemia Ⅲ hemostatic risk factors R upture of an atherosclerotic plaque with subsequent formation of an occlusive thrombus is the major cause of myocardial infarction. 1 The extrinsic coagulation system has been suggested to play a crucial role in the initiation of blood coagulation in atherosclerotic disease. 2 Tissue factor (TF) is an integral membrane protein that functions as a cofactor to enhance the proteolytic activity of activated factor VII (FVII a ) toward factor IX and factor X, which leads to the formation of a fibrin clot. 3 TF is synthesized in perturbed endothelial cells, 4 which may render them thrombogenic, and is also present in the cores of atherosclerotic plaques. 5 Thus, transient exposure of TF at the surface of atherosclerotic plaque or perturbed endothelial cells may cause low-grade triggering of blood coagulation. TF pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation, which exerts its function by neutralizing the catalytic activity of factor Xa and by feedback inhibition of the TF-FVII a complex. 6,7 Factor VII (FVII) is the first enzyme involved in the extrinsic pathway of blood coagulation. The major proportion of FVII circulates in plasma in the zymogen form, whereas low but significant levels appear in an activated form (FVII a ), which serves as the primer for triggering the clotting cascade. 8 -10 In epidemiological studies, the coagulation activity of factor VII (FVII c ) is positively correlated to serum triglycerides 11 (less consistently to serum chol...

Plasminogen Activator Inhibitor-1 and Tissue-Plasminogen Activator in Minority Adolescents with Type 2 Diabetes and Obesity

“…On the contrary, the PAI-1 activities decreased significantly. Both increased and decreased PAI-1 activities after fat loads have been reported (39,(42)(43)(44)(45)(46)(47). The difference in the postprandial PAI-1 responses has been explained by different genotypes of PAI-1, different fat types and content, and that PAI-1 has a circadian rhythm (PAI-1 concentrations decrease during the day) (39,44,48,49).…”

Boron supplementation and activated factor VII in healthy men

“…Initially, 31 apparently healthy men, aged 45 -65 y, volunteered to participate in the intervention study. Following a lifestyle and biochemical screen, 15 volunteers satisfied the following inclusion criteria: non-smokers, with a habitually low intake of fish (n-3 polyunsaturated fatty acids have previously been shown to lower postprandial factor VIIa; Nordoy et al, 2000) and a body mass index (BMI) of between 20 and 33 kg=m 2 . None of the volunteers was adhering to any form of special diet or taking dietary fatty acid supplements.…”

Uses and benefits of omega-3 ethyl esters in patients with cardiovascular disease

“…110 Across clinical studies, omega-3 fatty acids did not show a consistent effect on hemostatic variables including levels of fibrinogen, factor VII or VIII or von Willebrand factor. 60,111 Moreover, changes in levels of fibrinogen, factor VII or VIII, or von Willebrand factor generally did not significantly differ between recipients of 1000-6000 mg/day omega-3 EE and controls in healthy volunteers, 112 post-MI patients, 110 patients with mild hypertension, 81 patients with combined hyperlipidemia 109 or patients undergoing coronary artery bypass graft (CABG) surgery. 113 Bleeding time was prolonged in 40 post-MI patients after four weeks of 3400 mg/day EPA-DHA, without significant alteration of other hemostatic parameters, 114 and increased in one study in CAD patients.…”

“…107 In patients with CAD, fibrinolytic activity, as assessed by plasminogen activator inhibitor-I activity levels, was found to be increased by 1800 mg/day of EPA, 108 and by EPA-DHA 3400 mg/day. 109 A three-month randomized study comparing 850 mg/EPA-DHA with usual care in 77 post-MI patients showed no differences in levels of …”