title: Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus erythematosus: association with metabolic syndrome.
abstract: OBJECTIVE
  Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE.
  
  
  METHODS
  We assessed the effect of aspirin by measuring concentrations of the stable metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin.
  
  
  RESULTS
  Aspirin almost completely suppressed sTXB2 in control subjects to median 1.5 ng/ml (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was present in 15% (5 of 34) of the patients with SLE but not in control subjects (0 of 36) (P = 0.023). Incomplete responders were more likely to have metabolic syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C-reactive protein (CRP) (P = 0.018).
  
  
  CONCLUSIONS
  The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Kawai
authors.forename: Ingrid
authors.initials: I
authors.lastname: Avalos
authors.forename: Annette
authors.initials: A
authors.lastname: Oeser
authors.forename: John A
authors.initials: JA
authors.lastname: Oates
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Solus
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D051545:Cyclooxygenase 1 / Q000097:blood*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; D002097:C-Reactive Protein; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
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