title: Platelet thromboxane (11-dehydro-Thromboxane B2) and aspirin response in patients with diabetes and coronary artery disease.
abstract: Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes (DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2 (11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls (P = 0.024): female subjects (DM and controls) had 50.9% higher baseline 11dhTxB2 than males (P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM (71.7%) and controls (75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders (ASA "resistant") in DM than in controls (14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome (ACS) patients was 28.6 and 28.7%, in spite of a significant (81.6%) inhibition of urinary 11dhTxB2 (P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Lopez
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Kirk E
authors.initials: KE
authors.lastname: Guyer
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Ignacio Garcia De La
authors.initials: IG
authors.lastname: Torre
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Pitts
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.affiliation: Luis R Lopez, Kelly R Pitts, Corgenix Medical Corporation, Broomfield, CO 80020, United States.
authors.forename: Paul Rj
authors.initials: PR
authors.lastname: Ames
keywords: Aspirin; Cardiovascular disease; Diabetes; Platelets; Thromboxane
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