Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease.
OBJECTIVE
To assess the effect of simvastatin, hormone replacement therapy and their combination on soluble cell adhesion molecules and plasma lipids, in hypercholesterolaemic post-menopausal women with coronary artery disease.


METHODS
We studied 16 post-menopausal women with coronary artery disease and hypercholesterolaemia (total cholesterol >200mg x dl(-1) and LDL cholesterol >130 mg x dl(-1)). We compared simvastatin (20 mg daily) with hormone replacement therapy (0.625 mg conjugated oestrogen and 2.5 mg medroxyprogesterone acetate daily) and their combination, in a randomized, crossover, placebo controlled study. Each treatment period was 8 weeks long with a 4 week washout interval between treatments. Circulating cell adhesion molecules and plasma lipids were evaluated at the end of each treatment period.


RESULTS
All three active treatments--simvastatin, hormone replacement therapy and the combination therapy--significantly reduced total and LDL cholesterol, compared to placebo (P<0.001). Only hormone replacement therapy, alone and in combination with simvastatin, significantly decreased lipoprotein(a) when compared to placebo (P<0.05), whereas simvastatin had no significant effect. Likewise, hormone replacement therapy and the combination therapy significantly reduced the intercellular adhesion molecule (ICAM-1) plasma levels (P=0.03 and P=0.02, respectively), while simvastatin, which was superior to hormone replacement therapy in lowering total and LDL cholesterol, did not modify ICAM-1 levels; the combination therapy was not more effective than hormone replacement therapy alone in ICAM-1 reduction. Neither the effect, on any treatment when compared to placebo, of VCAM-1 nor E-selectin levels differed significantly.


CONCLUSIONS
Hormone replacement therapy may limit the inflammatory response to injury by modulating the expression of cell adhesion molecules from the endothelial cells, possibly in association with lipoprotein (a) reduction.
Sbarouni
E
E
2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Kroupis
C
C
Kyriakides
Z S
ZS
Koniavitou
K
K
Kremastinos
D T
DT
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP); D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin; D017258:Medroxyprogesterone Acetate