Comparison of effects of pravastatin and hormone therapy on soluble P-selectin and platelet P-selectin expression in postmenopausal hypercholesterolemic women.
OBJECTIVE
Recent trials have suggested an adverse early effect on cardiovascular risk of hormone therapy (HT) in postmenopausal women, an effect which could be due to an increase in arterial thrombosis via platelet activation. We examined the effect of HT on platelet surface expression of P-selectin, a marker of platelet activation, and plasma levels of soluble P-selectin, also believed to be a marker of platelet activation, and compared these effects with pravastatin, a drug proven to reduce cardiovascular events and reported to decrease both platelet and soluble P-selectin.


METHODS
Surface expression of platelet P-selectin, soluble P-selectin and fasting lipids were measured at baseline and 6 months in a randomized, double-blind study of postmenopausal hypercholesterolemic women comparing low-dose combined HT (1mg estradiol + 0.5 mg norethisterone acetate; n = 26) with pravastatin (n = 24).


RESULTS
After adjusting for baseline levels, HT and pravastatin produced similar reductions in soluble P-selectin (p < 0.0001 for both). The percentage of platelets expressing P-selectin was also reduced by pravastatin (p = 0.025), but there was a trend to an increase in platelet P-selectin expression with HT (p = 0.13), and a significant difference between pravastatin and HT in the changes in platelet P-selectin (p < 0.002). No relationship was evident between changes in soluble or platelet P-selectin and changes in lipids with either treatment.


CONCLUSIONS
In postmenopausal hypercholesterolemic women, both pravastatin and HT reduced soluble P-selectin levels, but only pravastatin reduced P-selectin expression on the surface of platelets. An implication of these findings is that the reduction in soluble P-selectin by HT may occur by a non-platelet related mechanism.
Peverill
Roger E
RE
Cardiology Unit, Centre for Heart and Chest Research, Monash University Department of Medicine, Monash Medical Centre, Clayton, Vic., Australia. roger.peverill@med.monash.edu.au
Smolich
Joseph J
JJ
Malan
Erica
E
Goldstat
Rebecca
R
Davis
Susan R
SR
D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D005215:Fasting; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008055:Lipids / Q000032:analysis; D008875:Middle Aged; D009640:Norethindrone / Q000009:adverse effects / Q000627:therapeutic use; D019007:P-Selectin / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects*; D017698:Postmenopause; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use*; D012044:Regression Analysis; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008055:Lipids; D019007:P-Selectin; D004958:Estradiol; D017035:Pravastatin; D009640:Norethindrone