title: Differential impact of inflammation on six laboratory assays measuring residual arachidonic acid-inducible platelet reactivity during dual antiplatelet therapy.
abstract: OBJECTIVE
  Inflammation has been postulated to modify the platelet response to aspirin treatment, thereby causing high on-treatment residual platelet reactivity (HRPR). Both high levels of inflammatory markers and HRPR have been linked to adverse cardiovascular events. We aimed to study the impact of inflammation on residual arachidonic acid (AA)-inducible platelet reactivity.
  
  
  METHODS
  In 288 patients receiving dual antiplatelet therapy, residual AA-inducible platelet reactivity was assessed using light transmission aggregometry (LTA), the VerifyNow assay, multiple electrode aggregometry (MEA) and the Impact-R. The levels of urinary 11-dehydro-thromboxane B2 (D-TXB2), serum thromboxane B2 (TXB2), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were determined using immunoassays.
  
  
  RESULTS
  The IL-6 level was found to be an independent predictor of platelet reactivity as determined according to LTA and D-TXB2 using a multiple linear regression analysis. Accordingly, patients with supramedian IL-6 levels exhibited significantly higher platelet reactivity than patients with inframedian IL-6 levels when determined according to LTA and D-TXB2 (both p ≤0.02). High IL-6 levels were associated with a 3.6-fold (95%CI 2.1-6.4) increased risk of HRPR, as defined according to D-TXB2, and a 3.4-fold (95%CI 1.4-8.3) increased risk of HRPR, as defined according to MEA. The HsCRP level was found to be an independent predictor of platelet reactivity when determined according to LTA, D-TXB2, the Impact-R and TXB2 using a multiple linear regression analysis. High hsCRP levels were associated with a 3.6-fold (95%CI 1.3-10) increased risk of HRPR, as defined according to LTA, and a 2.5-fold (95%CI 1.3-4.6) increased risk of HRPR, as defined according to TXB2.
  
  
  CONCLUSIONS
  Increased levels of inflammatory markers are independently associated with residual AA-inducible platelet reactivity in patients receiving dual antiplatelet treatment.
authors.affiliation: Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Seidinger
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Kopp
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
mesh_terms: D000368:Aged; D001095:Arachidonic Acids / Q000737:chemistry*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D002097:C-Reactive Protein / Q000737:chemistry; D004563:Electrochemistry; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000473:pathology*; D015850:Interleukin-6 / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000652:urine
chemical_list: D001095:Arachidonic Acids; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D002097:C-Reactive Protein; D001241:Aspirin