Effects of atorvastatin and rosuvastatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia.
OBJECTIVE
We examined the time-dependent effects of atorvastatin and rosuvastatin on in vivo oxidative stress and platelet activation, to assess whether these phenomena are related to any pleiotropic effect of any statin or to their LDL-lowering effect. We also asked whether the presence of specific allele frequencies in carriers of the 3'UTR/lectin-like oxidized LDL receptor-1 (LOX-1) polymorphism may influence the effect of either statin.


METHODS
We included 60 hypercholesterolemic subjects, previously screened for LOX-1 3'UTR polymorphism, randomized, according to genetic profile (15 T and 15 C carriers for each arm), to atorvastatin 20mg/day or rosuvastatin 10mg/day.


RESULTS
After 8 weeks, atorvastatin and rosuvastatin were associated with comparable, significant reductions in LDL cholesterol (40.8% and 43.6%, respectively), plasma hs-CRP (9.5% vs. 13.8%), urinary 11-dehydro-thromboxane (TX) B(2) (38.9% vs. 27.1%) and 8-iso-prostaglandin (PG) F(2α) (39.4% vs. 19.4%). The impact of rosuvastatin or atorvastatin on CRP, 8-iso-PGF(2α), and 11-dehydro-TXB(2) did not differ according to the LOX-1 haplotype. On multiple regression analyses, only CRP and LDL were independent predictors of 11-dehydro-TXB(2), and only LDL was a significant predictor of 8-iso-PGF(2α).


CONCLUSIONS
Both atorvastatin and rosuvastatin cause comparable reductions of thromboxane-dependent platelet activation, lipid peroxidation and inflammation. The presence of 3'UTR/LOX-1 polymorphism does not affect the changes induced by either statin.
Center for Atherosclerosis Research, University of Siena, v.le Bracci, 53100 Siena, Italy. puccetti@unisi.it
Luca
L
Puccetti
Francesca
F
Santilli
Anna Laura
AL
Pasqui
Stefano
S
Lattanzio
Rossella
R
Liani
Federica
F
Ciani
Elisabetta
E
Ferrante
Giovanni
G
Ciabattoni
Francesca
F
Scarpini
Anna
A
Ghezzi
Alberto
A
Auteri
Giovanni
G
Davì
D020413:3' Untranslated Regions; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015539:Platelet Activation; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011454:Prostaglandins A / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D012044:Regression Analysis; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism*
D020413:3' Untranslated Regions; C117466:8-isoprostaglandin A2; D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D008055:Lipids; D011454:Prostaglandins A; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D013929:Thromboxane B2; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin