Published online Apr 15, 2014. doi: 10.4239/wjd.v5.i2.115
Revised: February 25, 2014
Accepted: March 11, 2014
Published online: April 15, 2014
Processing time: 126 Days and 11.8 Hours
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.
Core tip: The effect of aspirin (ASA) on platelet thromboxane (11dhTxB2) generation in diabetes (DM) and symptomatic cardiovascular disease (CVD) was reviewed. Consistent with a heightened platelet hyperactive background, baseline 11dhTxB2 was significantly higher in DM and acute coronary syndrome (ACS) than healthy individuals. ASA ingestion inhibited 11dhTxB2 in all subjects, but there were more ASA poor-responders (ASA “resistant”) in DM (14.8%) and ACS (28.7%) than controls (8.4%). Only post-ASA 11dhTxB2 levels predicted adverse cardiovascular outcomes. ASA poor-responders had higher isoprostane (8-isoPGF2α) levels suggesting an underlying systemic oxidative inflammatory process not affected by ASA that may maintain platelet hyperactivity in DM and atherothrombotic CVD.