title: Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors.
abstract: The effects of cerivastatin and fenofibrate on proteins involved in haemostasis and on markers of inflammation were investigated in otherwise healthy middle-aged males with combined hyperlipidemia. Besides classical risk factors, other so-called novel risk factors for coronary artery disease are seen to be playing an increasingly important role in the development and progression of atherosclerosis. Thirty-eight males, aged 49 +/-5 years were randomised to 12 weeks treatment either with cerivastatin at a daily dose of 0.2 mg to 0.4 mg to achieve the LDL cholesterol goal of <3.0 mM, or with fenofibrate 250 mg daily. Fasting serum lipids, homocysteine, total and free tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) antigen and activity, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured. No change in homocysteine level was observed in the cerivastatin group, while after fenofibrate administration it increased (p <0.0001). Total TFPI decreased significantly after cerivastatin (p = 0.002), but not after fenofibrate. Free TFPI did not decrease after either drug. Neither drug affected (t-PA) antigen and activity, while fenofibrate increased PAI-1 antigen (p <0.05) and activity (p <0.05). Cerivastatin decreased serum CRP values by 49.5% (p = 0.001), and fenofibrate by 29.8% (p = 0.03). The decreases of CRP in the two groups differed significantly (p = 0.04). IL-6 levels decreased significantly in the fenofibrate group (39%; p <0.0001), but not in the cerivastatin group (15%; p = 0.24) No significant decreases were observed for TNF-alpha. Cerivastatin had neutral effects on fibrinolysis, homocysteine or coagulation. On the other hand, fenofibrate increased PAI-1 antigen and activity and homocysteine, and did not affect coagulation. Both cerivastatin and fenofibrate reduced CRP levels, the decrease being significantly greater after cerivastatin. Fenofibrate also significantly decreased IL-6.
authors.affiliation: University Clinical Centre, Department of Angiology, Zaloska 7, 1525 Ljubljana, Slovenia. miran.sebestjen@trnovo.kclj.si
authors.forename: Miran
authors.initials: M
authors.lastname: Sebestjen
authors.forename: Irena
authors.initials: I
authors.lastname: Keber
authors.forename: Branka
authors.initials: B
authors.lastname: Zegura
authors.forename: Sasa
authors.initials: S
authors.lastname: Simcic
authors.forename: Mojca
authors.initials: M
authors.lastname: Bozic
authors.forename: Martine Migaud
authors.initials: MM
authors.lastname: Fressart
authors.forename: Mojca
authors.initials: M
authors.lastname: Stegnar
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000032:analysis; D001835:Body Weight; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D002995:Clofibric Acid / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D011345:Fenofibrate / Q000008:administration & dosage / Q000494:pharmacology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D012307:Risk Factors
chemical_list: D001779:Blood Coagulation Factors; D008078:Cholesterol, LDL; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D011725:Pyridines; D006710:Homocysteine; D002995:Clofibric Acid; D002097:C-Reactive Protein; C086276:cerivastatin; D011345:Fenofibrate