title: Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry.
abstract: Hyperlipidemia is a well established risk factor for cardiovascular disease and atherothrombotic events, in which platelet activation also plays a significant role. However, very few studies have addressed platelet activation in hypercholesterolemia, the potential effect of lipid lowering drugs upon platelet hyperfunction, and the question of whether changes in the latter are correlated to normalization of plasma lipids. This study used whole blood flow cytometry to assess in vivo and in vitro platelet activation in a group of 33 patients with hypercholesterolemia, and also the ex vivo effect of atorvastatin (20 mg/day) upon such activation. A control group of 40 normolipidemic volunteers matched in terms of age, sex and added risk factors to the patient group was used. The results showed that hypercholesterolemic patients had in vivo a significantly greater percentage of GPIIb/IIIa- and phosphatidylserine-positive platelets compared with the control group (4.62+/-3.51% and 2.58+/-1.19% versus 2.73+/-1.08% and 1.54+/-0.68%, respectively). In vitro response of CD62 expression to thrombin was also greater in the patients than in the controls (92.51+/-6.00% versus 89.63+/-10.72%, p<0.05). Atorvastatin therapy normalized platelet hyperfunction in the patients studied and reduced GPIIb/IIIa response to ADP (from 82.65+/-6.43% to 75.84+/-4.89%, p<0.01). A significant correlation can be seen between such normalization and the decrease in plasma levels of total and LDL cholesterol.
authors.affiliation: Department of Internal Medicine, Clinic University Hospital, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Labiós
authors.forename: Marcial
authors.initials: M
authors.lastname: Martínez
authors.forename: Francisco
authors.initials: F
authors.lastname: Gabriel
authors.forename: Victoria
authors.initials: V
authors.lastname: Guiral
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez
authors.forename: Justo
authors.initials: J
authors.lastname: Aznar
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011758:Pyrroles; D000244:Adenosine Diphosphate; D002784:Cholesterol; D000069059:Atorvastatin; D013917:Thrombin