title: Urinary 11-Dehydro-Thromboxane B2and Mortality in Patients With Stable Coronary Artery Disease.
abstract: Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2(TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2(11dhTxB2), an inactive metabolite of TxA2from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (±SD) of 67 ± 10 and 65 ± 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2(p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.
authors.affiliation: Baylor University Medical Center, Dallas, Texas; Baylor Heart and Vascular Institute, Dallas, Texas; Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas; The Heart Hospital Baylor Plano, Plano, Texas; Texas A&M Health Science Center College of Medicine, Dallas Campus, Dallas, Texas. Electronic address: peteramccullough@gmail.com.
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
authors.affiliation: Baylor Heart and Vascular Institute, Dallas, Texas; Texas A&M Health Science Center College of Medicine, Dallas Campus, Dallas, Texas; Baylor Research Institute, Dallas, Texas.
authors.forename: Anupama
authors.initials: A
authors.lastname: Vasudevan
authors.affiliation: Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas; Baylor All Saints Medical Center, Fort Worth, Texas.
authors.forename: Mohanakrishnan
authors.initials: M
authors.lastname: Sathyamoorthy
authors.affiliation: Baylor University Medical Center, Dallas, Texas; Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas; Texas A&M Health Science Center College of Medicine, Dallas Campus, Dallas, Texas.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Schussler
authors.affiliation: Baylor University Medical Center, Dallas, Texas; Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Velasco
authors.affiliation: Corgenix Inc., Broomfield, Colorado.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Lopez
authors.affiliation: Baylor Research Institute, Dallas, Texas; Institute of Metabolic Disease, Dallas, Texas.
authors.forename: Caren
authors.initials: C
authors.lastname: Swift
authors.affiliation: Baylor Research Institute, Dallas, Texas; Institute of Metabolic Disease, Dallas, Texas.
authors.forename: Margarita
authors.initials: M
authors.lastname: Peterson
authors.affiliation: Baylor Research Institute, Dallas, Texas; Institute of Metabolic Disease, Dallas, Texas.
authors.forename: Jenna
authors.initials: J
authors.lastname: Bennett-Firmin
authors.affiliation: Baylor Research Institute, Dallas, Texas; Institute of Metabolic Disease, Dallas, Texas.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Baylor Research Institute, Dallas, Texas; Institute of Metabolic Disease, Dallas, Texas.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000401:mortality* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013781:Texas / Q000453:epidemiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D015415:Biomarkers; D008055:Lipids; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2