title: Residual thromboxane activity and oxidative stress: influence on mortality in patients with stable coronary artery disease.
abstract: BACKGROUND
  Aspirin use is effective in the prevention of cardiovascular disease; however, not all patients are equally responsive to aspirin. Oxidative stress reflected by F2-isoprostane [8-iso-prostaglandin-F2α (8-IsoPGF2α)] is a potential mechanism of failure of aspirin to adequately inhibit cyclooxygenase-1. The objective was to examine the relation between all-cause mortality and the concentrations of urinary 11-dehydro thromboxane B2 (11dhTxB2) and 8-IsoPGF2α in patients with stable coronary artery disease (CAD).
  
  
  METHODS
  The data for this analysis are from a prospective study in which patients were categorized into four groups based on the median values of 11dhTxB2 and 8-IsoPGF2α.
  
  
  RESULTS
  There were 447 patients included in this analysis with a median (range) age of 66 (37-91) years. The median (range) values of 11dhTxB2 and 8-IsoPGF2α were 1404.1 (344.2-68296.1) and 1477.9 (356.7-19256.3), respectively. A total of 67 (14.9%) patients died over a median follow-up of 1149 days. The reference group for the Cox proportional hazards survival analysis was patients with values of 11dhTxB2 and 8-IsoPGF2α below their corresponding medians. Adjusting for the age and sex, patients with values of 11dhTxB2 greater than the median had a significantly higher risk of mortality when compared with the reference group (high 11dhTxB2 and low 8-IsoPGF2αadj: hazard ratio: 3.2, 95% confidence interval: 1.6-6.6, P=0.002; high 11dhTxB2 and 8-IsoPGF2αadj: hazard ratio: 3.6, 95% confidence interval: 1.8-7.3, P<0.001). The findings were similar when we adjusted for the comorbidities of cancer, kidney function, and ejection fraction.
  
  
  CONCLUSIONS
  We found that 11dhTxB2 appears to be a better prognostic marker for mortality as compared with 8-IsoPGF2α, suggesting aspirin resistance itself is a stronger independent determinant of death in CAD patients treated with aspirin.
authors.affiliation: aBaylor Heart and Vascular Institute bDepartment of Internal Medicine, Texas A&M Health Science Center, College of Medicine, Dallas Campus cBaylor Scott & White Research Institute dInstitute of Metabolic Disease eDivision of Cardiology, Baylor Jack and Jane Hamilton Heart and Vascular Hospital fDivision of Cardiology, Baylor University Medical Center, Dallas gDivision of Cardiology, Baylor All Saints Medical Center, Fort Worth hDivision of Cardiology, The Heart Hospital Baylor Plano, Plano, Texas iCorgenix Inc., Broomfield, Colorado, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Vasudevan
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Tecson
authors.forename: Mohanakrishnan
authors.initials: M
authors.lastname: Sathyamoorthy
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Schussler
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Velasco
authors.forename: Luis R
authors.initials: LR
authors.lastname: Lopez
authors.forename: Caren
authors.initials: C
authors.lastname: Swift
authors.forename: Margarita
authors.initials: M
authors.lastname: Peterson
authors.forename: Jeanna
authors.initials: J
authors.lastname: Bennett-Firmin
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D002423:Cause of Death / Q000639:trends; D003324:Coronary Artery Disease / Q000401:mortality / Q000517:prevention & control / Q000652:urine*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost; D001241:Aspirin