title: Association of plasma concentrations of salicylic acid and high on ASA platelet reactivity in type 2 diabetes patients.
abstract: BACKGROUND
  The objective of this study was to investigate the association between plasma concentrations of salicylic acid (SA) and other minor acetylsalicylic acid (ASA) metabolites and high on ASA platelet reactivity assessed with different methods in type 2 diabetic patients (T2DM).
  
  
  METHODS
  Study cohort consisted of 293 T2DM patients on chronic ASA therapy. Platelet function inhibition was analyzed using measurements of serum thromboxane B2 (S-TxB2), VerifyNow Aspirin and Platelet Function Analyzer (PFA)-100 assays. The concentration of ASA metabolites in plasma was measured with a high-performance liquid chromatography (HPLC).
  
  
  RESULTS
  In logistic regression analysis both ASA dose/kg of body weight and plasma SA concentration were found to be predictive of S-TxB2 concentrations above 0.72 ng/mL cut-off point (OR 16.9, 95% CI 2.29-125.8, p = 0.006 and OR 5.34, 95% CI 2.67-10.68, p < 0.001, respectively). When using the VerifyNow Aspirin Assay, the concentrations of SA were significantly lower (p = 0.007) in the group with high on ASA platelet reactivity when compared with the group with normal on ASA platelet reactivity. In logistic regression analysis plasma SA concentration was found to be predictive of VerifyNow Aspirin Reaction Units (ARU) ≥ 550 (OR 3.86, 95% CI 1.86-8.00, p < 0.001).
  
  
  CONCLUSIONS
  Our study suggests that disturbances of pharmacokinetic mechanisms might contribute to lower plasma SA levels, and subsequently incomplete inhibition of thromboxane A2 synthesis as measured with S-TxB2 concentrations and increased platelet reactivity measured with VerifyNow in T2DM patients.
authors.affiliation: mpostula@wum.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Postula
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
authors.forename: Marek
authors.initials: M
authors.lastname: Rosiak
authors.forename: Adam
authors.initials: A
authors.lastname: Przybylkowski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaplon-Cieslicka
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grygorowicz
authors.forename: Ewa
authors.initials: E
authors.lastname: Trzepla
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Filipiak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Czlonkowski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
mesh_terms: D000368:Aged; D001241:Aspirin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D051545:Cyclooxygenase 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011044:Poland; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D020156:Salicylic Acid / Q000097:blood* / Q000493:pharmacokinetics; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D020156:Salicylic Acid; D001241:Aspirin