Atorvastatin and thrombogenicity of the carotid atherosclerotic plaque: the ATROCAP study.
Statins appear to have beneficial effects on fibrous cap stabilisation but their effects on plaque thrombogenicity have not been reported. To evaluate the thrombogenicity of human carotid plaques before and after atorvastatin treatment, 59 patients with bilateral carotid stenosis eligible for two-step carotid endoarterectomy (CEA) were randomly assigned to atorvastatin, 20 mg/day, or placebo. Histological and immunohistochemical analyses, Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) antigens (Ag) and TF activity were determined in endoarterectomy specimens obtained at baseline and after treatment. Mean TFAg and TFPIAg levels from plaques removed at the first CEA were 55 +/- 56 and 32 +/- 26 pg/mg. After placebo, TFAg and TFPIAg content was higher in the second than the first CEA. Plaques removed at the second CEA from atorvastatin-treated patients had a lower macrophage content than plaques at the first CEA. TFAg and TFPIAg levels, and TF activity in plaques after atorvastatin treatment were lower (respectively 29, 18% and 56%) than after placebo. These findings indicate that atorvastatin reduce the inflammatory/thrombotic phenotype of carotid plaque, suggesting that these drugs may indeed have a beneficial effect on cerebrovascular events.
Cortellaro
Michele
M
University of Milan, Italy. centrorc@mailserver.unimi.it
Cofrancesco
Elisabetta
E
Arbustini
Eloisa
E
Rossi
Francesca
F
Negri
Andrea
A
Tremoli
Eiena
E
Gabrielli
Livio
L
Camera
Marina
M
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D013925:Thromboplastin / Q000032:analysis / Q000187:drug effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D011758:Pyrroles; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D000069059:Atorvastatin