title: Soluble P-selectin level correlates with acetylsalicylic acid but not with clopidogrel response in patients with stable coronary artery disease after a percutaneous coronary intervention.
abstract: BACKGROUND
  Impaired response to dual antiplatelet therapy is associated with worse cardiovascular outcome. Besides antiplatelet effects, there is evidence that both clopidogrel and acetylsalicylic acid (ASA) have anti-inflammatory properties. However, little is known about the relationship between platelet function and inflammation under dual antiplatelet therapy in patients with stable coronary artery disease.
  
  
  OBJECTIVE
  The purpose of the study was to investigate the correlation of platelet function with soluble (s)P-selectin and soluble (s)CD40L in patients undergoing elective percutaneous coronary intervention. Poor response to ASA and clopidogrel could lead to increased levels of inflammatory markers.
  
  
  METHODS
  A total of 148 patients were included. Eighty percent of the patients were on 100 mg ASA and all patients were clopidogrel naive. They underwent percutaneous coronary intervention and received a loading dose of 600 mg clopidogrel. Platelet function was assessed by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein analysis at baseline, 24 h after loading, and after 1 month of maintenance therapy, respectively. Plasma levels of sP-selectin and sCD40L were measured. To classify low responders to clopidogrel, patients were screened for genetic variants determining clopidogrel absorption and metabolization.
  
  
  RESULTS
  sP-selectin levels correlated with LTA findings after stimulation with arachidonic acid (P=0.012). Further, in addition to decreased platelet reactivity observed on LTA, lower sP-selectin levels were seen in patients under ASA therapy (P=0.004). CYP2C19*2 allele carriers had a higher platelet reactivity after clopidogrel loading measured by adenosine diphosphate-induced aggregation in LTA (P=0.008) and vasodilator-stimulated phosphoprotein phosphorylation (P=0.035); however, there was no difference in the inflammatory markers. Multiple regression analysis showed that variables significantly related to sP-selectin plasma levels were sCD40L (P<0.001), LTA after stimulation with arachidonic acid (P<0.001), adenosine diphosphate (20 µmol/l, P=0.009), collagen (P<0.001), and ejection fraction (P=0.001).
  
  
  CONCLUSIONS
  sP-selectin was decreased in patients receiving ASA but did not reflect a CYP2C19*2-defined clopidogrel response. This underlines that sP-selectin is a useful marker for ASA, but not for clopidogrel response, in stable coronary artery disease.
authors.affiliation: Department of Internal Medicine/Cardiology, German Heart Institute Berlin, 13353 Berlin, Germany. jkaufmann@DHZB.de
authors.forename: Jan
authors.initials: J
authors.lastname: Kaufmann
authors.forename: Ernst
authors.initials: E
authors.lastname: Wellnhofer
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
authors.forename: Daniel
authors.initials: D
authors.lastname: Urban
authors.forename: Heike
authors.initials: H
authors.lastname: Meyborg
authors.forename: Tobias
authors.initials: T
authors.lastname: Hauptmann
authors.forename: Aline
authors.initials: A
authors.lastname: Müller
authors.forename: Martin
authors.initials: M
authors.lastname: Meixner
authors.forename: Kristof
authors.initials: K
authors.lastname: Graf
authors.forename: Eckart
authors.initials: E
authors.lastname: Fleck
authors.forename: Philipp
authors.initials: P
authors.lastname: Stawowy
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D062645:Percutaneous Coronary Intervention; D010750:Phosphoproteins / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; C546937:SELP protein, human; D000098662:Vasodilator-Stimulated Phosphoprotein; D023201:CD40 Ligand; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin