title: Time-dependent effect of statins on platelet function in hypercholesterolaemia.
abstract: BACKGROUND
  Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL-C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day-1), atorvastatin (10 mg day-1), fluvastatin (40 mg day-1) and pravastatin (40 mg day-1) on platelet function in hypercholesterolaemic subjects with relation to (LDL-C), oxidized-LDL (ox-LDL) and antiport mechanism modifications.
  
  
  METHODS
  Sixteen subjects were assigned to each treatment (40 males, 24 females, mean age 48.7 +/- 13.4, LDL-C 5.13 +/- 0,23 mmol L-1) and evaluated for platelet surface P-selectin (P-sel), lipid profile, ox-LDL, platelet-associated ox-LDL (Pox-LDL), platelet cholesterol content, antiport mechanisms, and intracellular and systemic NO synthase every 7 days for one month.
  
  
  RESULTS
  Our data show a strong relation between enhanced P-sel and Pox-LDL (r = 0.68, P < 0.01). Simvastatin, atorvastatin, fluvastatin and pravastatin reduce platelet activity after 1, 2, 3 and 4 weeks of treatment, respectively (P < 0.001, P < 0.001, P < 0.01, P < 0.05). Pox-LDL are modulated early by simvastatin, atorvastatin and fluvastatin Pox-LDL (r = 0.66, 0.65 and 0.52; P < 0.001, 0.001 and 0.01, respectively) whereas LDL-C and ox-LDL reductions associated to modifications of antiport activity act later. Moreover, they are the most relevant finding in pravastatin-related subjects.
  
  
  CONCLUSIONS
  Our data suggest a different impact of several statins on platelet function, which is initially related to interference with Pox-LDL rather than LDL-C reduction.
authors.affiliation: Department of Clinical Medicine and Immunological Sciences, Center for Metabolic Diseases and Atherosclerosis, University of Siena, Siena, Italy. puccetti@unisi.it
authors.forename: L
authors.initials: L
authors.lastname: Puccetti
authors.forename: A L
authors.initials: AL
authors.lastname: Pasqui
authors.forename: M
authors.initials: M
authors.lastname: Pastorelli
authors.forename: G
authors.initials: G
authors.lastname: Bova
authors.forename: M
authors.initials: M
authors.lastname: Cercignani
authors.forename: A
authors.initials: A
authors.lastname: Palazzuoli
authors.forename: P
authors.initials: P
authors.lastname: Angori
authors.forename: A
authors.initials: A
authors.lastname: Auteri
authors.forename: F
authors.initials: F
authors.lastname: Bruni
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D017920:Antiporters / Q000378:metabolism; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000032:analysis; D008078:Cholesterol, LDL / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D017920:Antiporters; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008077:Lipoproteins, LDL; D019007:P-Selectin; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000077340:Fluvastatin; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D017035:Pravastatin