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Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry
Authors:Labiós Manuel  Martínez Marcial  Gabriel Francisco  Guiral Victoria  Martínez Elena  Aznar Justo
Institution:Department of Internal Medicine, Clinic University Hospital, Valencia, Spain.
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.
Keywords:ADP  adenosin diphosphate  LDL-C  low-density lipoproteins cholesterol  HDL-C  high-density lipoproteins cholesterol  TC  total cholesterol  GPIIb/IIIa*  GPII/IIIa in its active form  CD62  P-selectin  PS  phosphatidylserine  CD63  glycoprotein 53  HMG-COA  3-hydroxy-3-methylglutaryl-coenzyme A  BMI  body mass index  bpm  beats per minute  g  grams  ALT  alanine amino transferase  AST  aspartate amino transferase  CK  creatin kinase  ALP  alkaline phosphatase  HL  hyperlipidemic patients  ATOR  atorvastatin  m  month  ionoph  calcium ionophore A23187  Th  thrombin  ns  non significant
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