Alterations in the extrinsic pathway in hypertriglyceridemia do not cause a 'procoagulant state': effects of bezafibrate therapy.
Hypertriglyceridemia (HTG) is an independent risk factor for cardiovascular disease (CVD). Hemostatic variables [factor VII antigen (FVIIag), factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), free and endothelial-associated (EC) tissue factor pathway inhibitor (TFPI) antigen, pre- and post-heparin total TFPI activity, EC-TFPI activity, prothrombin fragment 1 + 2 (F1 + 2), fibrinogen and D-dimer] were compared between 18 HTG patients and 20 controls to investigate whether HTG is associated with alterations in the extrinsic pathway and whether such alterations create a procoagulant state, as expressed by F1 + 2 and D-dimer levels. In addition, the effects of bezafibrate therapy (6 weeks, 400 mg/day) on these variables were studied in 18 HTG patients in a double-blind, placebo-controlled, cross-over study. FVIIag, FVIIc, free TFPI and fibrinogen were significantly higher in HTG patients (by 44, 30, 45 and 31%, respectively; all P < 0.02), while FVIIa, EC-TFPIag and activity, total TFPI activities, F1 + 2 and D-dimer levels were similar in patients and controls. Bezafibrate reduced serum TG and fibrinogen levels (by 62 and 20%, respectively; both P < 0.001), whereas the other hemostatic variables were unaffected. In conclusion, the observed alterations in the extrinsic pathway in HTG are not associated with a procoagulant state. In contrast, the presence of elevated fibrinogen levels in HTG might enhance the risk for CVD. Bezafibrate therapy improved the adverse lipid profile and decreased fibrinogen levels in HTG patients.
Jonkers
I J
IJ
Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
de Man
F H
FH
van Tilburg
N H
NH
van der Laarse
A
A
Sandset
P M
PM
Smelt
A H
AH
Bertina
R M
RM
D000328:Adult; D000941:Antigens / Q000187:drug effects / Q000378:metabolism; D001629:Bezafibrate / Q000494:pharmacology / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000378:metabolism*; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism; D015942:Factor VIIa / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*
D000941:Antigens; D001779:Blood Coagulation Factors; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; C042580:factor VII clotting antigen; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D015942:Factor VIIa; D001629:Bezafibrate