Gender differences in blood thrombogenicity in hyperlipidemic patients andresponse to pravastatin

Thrombotic risk in hyperlipidemic women and its response to lipid therapy i s unknown. We prospectively studied 28 men and 29 women with high low-densi ty lipoprotein (LDL) cholesterol during 6 months of therapy with pravastati n. Women had significantly higher high- density lipoprotein (HDL) cholester ol (54.2 +/- 1.7 vs 39.5 +/- 2.2 mg/dl, p <0.01), lower prevalence of coron ary artery disease (41% vs 67%, p = 0.04), and otherwise similar baseline c haracteristics 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 le vels throughout the study. Systemic hemostatic markers and thrombus formati on under dynamic flow conditions were evaluated at baseline, and at 3 and 6 months of follow-up. Prothrombin fragment F-1.2, a marker of thrombin gene ration, 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 va riance), whereas it remained unchanged in men. Plasminogen activator inhibi tor-1 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% i n women and 11.8% in men at 6 months compared with baseline. Fibrinogen sho wed an increase in both genders at follow-up. Thrombus formation was simila r at baseline between the 2 genders, and decreased at 3 and 6 months compar ed 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, in cluding 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 ha d a comparable thrombotic and/or fibrinolytic profile to men and even evide nce 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 mont hs of follow-up. (C) 1999 by Excerpta Medica, Inc.