title: Gender differences in blood thrombogenicity in hyperlipidemic patients and response to pravastatin.
abstract: Thrombotic risk in hyperlipidemic women and its response to lipid therapy is unknown. We prospectively studied 28 men and 29 women with high low-density lipoprotein (LDL) cholesterol during 6 months of therapy with pravastatin. Women had significantly higher high-density lipoprotein (HDL) cholesterol (54.2 +/- 1.7 vs 39.5 +/- 2.2 mg/dl, p <0.01), lower prevalence of coronary artery disease (41% vs 67%, p = 0.04), and otherwise similar baseline characteristics compared with men. Both genders achieved a 33% reduction in LDL at 6 weeks (188 +/- 6 to 133 +/- 5 mg/dl) and maintained similar LDL levels throughout the study. Systemic hemostatic markers and thrombus formation under dynamic flow conditions were evaluated at baseline, and at 3 and 6 months of follow-up. Prothrombin fragment F1.2, a marker of thrombin generation, was higher in women versus men at baseline (2.4 +/- 0.2 vs 1.4 +/- 0.3 nmol/L, p = 0.02). The levels decreased in women to 2.0 +/- 0.3 nmol/L at 3 months and to 1.6 +/- 0.2 nmol/L at 6 months (p <0.045, analysis of variance), whereas it remained unchanged in men. Plasminogen activator inhibitor-I significantly decreased at 3 and 6 months of follow-up: by 12.6% and 18.7%, respectively, in women, and by 18.8% and 23.5%, respectively, in men. Similarly, tissue plasminogen activator decreased significantly by 7.4% in women and 11.8% in men at 6 months compared with baseline. Fibrinogen showed an increase in both genders at follow-up. Thrombus formation was similar at baseline between the 2 genders, and decreased at 3 and 6 months compared with baseline by 12.5% and 29.5% in women, and by 18.6% and 19.4% in men (p <0.04 at 6 months vs baseline in both men and women). Other markers, including C-reactive protein, fibrinopeptide A, D-dimer, and factor VIIa, did not differ between genders and did not change with therapy. Thus, despite higher HDL, and lower incidence of coronary disease, women with high LDL had a comparable thrombotic and/or fibrinolytic profile to men and even evidence of increased thrombin generation at baseline. Blood thrombogenicity was reduced with pravastatin in both genders; in addition, thrombin generation was gradually reduced in women to a level similar to that of men by 6 months of follow-up.
authors.affiliation: Cardiovascular Institute, Mount Sinai Medical Center, New York, New York, USA. gdd1@mhg.edu
authors.forename: G
authors.initials: G
authors.lastname: Dangas
authors.forename: D A
authors.initials: DA
authors.lastname: Smith
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: A H
authors.initials: AH
authors.lastname: Unger
authors.forename: J H
authors.initials: JH
authors.lastname: Shao
authors.forename: P
authors.initials: P
authors.lastname: Meraj
authors.forename: A M
authors.initials: AM
authors.lastname: Cohen
authors.forename: D
authors.initials: D
authors.lastname: Levine
authors.forename: J T
authors.initials: JT
authors.lastname: Fallon
authors.forename: J A
authors.initials: JA
authors.lastname: Ambrose
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use*; D011516:Prothrombin / Q000378:metabolism; D012737:Sex Factors; D013917:Thrombin / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005340:Fibrinogen; D013917:Thrombin; D017035:Pravastatin