title: Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia.
abstract: Elevated plasma fibrinogen level is known to progress atherosclerosis and to be one of the risk factors for the occurrence of cardiovascular diseases. The objective of this study is to evaluate the changes in plasma fibrinogen level and blood rheology in patients with type II hyperlipoproteinemia before and after random administrations of HMG-CoA (3-hydroxy-e-methylglutaryl-cocarboxylase-A) reductase inhibitors, pravastatin sodium and simvastatin, and compare with results in normal subjects. Of a total of 28 patients with type II primary hyperlipoproteinemia with > 230 mg/dl fasting total plasma cholesterol, 16 patients (mean, 59.7 years old) were administered 10-15 mg/day of pravastatin sodium for an average of 10.2 weeks, and 12 patients (mean, 62.0 years old) were administered 5-10 mg/day of simvastatin for an average of 13.9 weeks. Patients were evaluated before and after drug administration and results were compared with those of 16 normal subjects of similar age (mean, 56.9 years old). Blood viscosities were measured using a cone-plate viscometer (Biorheolizer, BRL-1000, Japan). The following were measured before and after drug administration: whole blood viscosity at shear rates of 75-375 s-1, corrected blood viscosity at low (112.5 s-1) and high (225.0 s-1) shear rates for the standard hematocrit of 45%, plasma viscosity, hematocrit, total protein, serum albumin, and plasma fibrinogen. Total cholesterol level was significantly decreased (from 270 to 225, mg/dl, mean values; P < 0.0007) an average of 10.2 weeks after start of pravastatin sodium administration. In addition to the reductions of whole blood viscosity, at every shear rate examined, corrected blood viscosity, and plasma viscosity, plasma fibrinogen levels were significantly decreased (from 354 to 309 mg/dl, mean values; P < 0.0007) after start of pravastatin sodium administration. Fibrinogen level and blood rheology were not significantly changed after start of simvastatin administration despite similar significant reductions in total cholesterol level (from 260 to 207 mg/dl, mean values; P < 0.0001) to those in the case of pravastatin sodium. From the results, we conclude that administration of pravastatin sodium, but not simvastatin, reduced the plasma fibrinogen level and blood viscosities to normal levels in type II hyperlipoproteinemic patients while both drugs reduced total cholesterol level. The hydrophilicity and a small binding capacity with plasma protein of pravastatin sodium may be responsible in part for the beneficial hemorheologic effects observed in the patients with type II hyperlipoproteinemia. Further investigations should be conducted to confirm the findings observed.
authors.affiliation: Second Department of Internal Medicine, Kagawa Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Kitadai
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Izumi
authors.forename: N
authors.initials: N
authors.lastname: Hosomi
mesh_terms: D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D001809:Blood Viscosity; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006400:Hematocrit; D018056:Hemorheology / Q000187:drug effects*; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood* / Q000188:drug therapy; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood
chemical_list: D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D005340:Fibrinogen; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin