Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia.
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.
Nordøy
A
A
Department of Medicine, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. arne.nordoy@unn.no
Svensson
B
B
Hansen
J-B
JB
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000097:blood; D000069059:Atorvastatin; D015942:Factor VIIa / Q000032:analysis / Q000378:metabolism; D005215:Fasting; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D019518:Postprandial Period; D011516:Prothrombin; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D019851:Thrombophilia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D015525:Fatty Acids, Omega-3; D006538:Heptanoic Acids; D010446:Peptide Fragments; D011758:Pyrroles; D014280:Triglycerides; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D000069059:Atorvastatin; D015942:Factor VIIa