Residual thromboxane activity and oxidative stress: influence on mortality in patients with stable coronary artery disease

Background Aspirin use is effective in the prevention of cardiovascular disease; however, not all patients are equally responsive to aspirin. Oxidative stress reflected by F-2-isoprostane [8-iso-prostaglandin-F2 alpha (8-IsoPGF2 alpha)] 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 B-2 (11dhTxB(2)) and 8-IsoPGF2 alpha 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 11dhTxB(2) and 8-IsoPGF2 alpha. Results There were 447 patients included in this analysis with a median (range) age of 66 (37-91) years. The median (range) values of 11dhTxB(2) and 8-IsoPGF2 alpha 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 11dhTxB(2) and 8-IsoPGF2 alpha below their corresponding medians. Adjusting for the age and sex, patients with values of 11dhTxB(2) greater than the median had a significantly higher risk of mortality when compared with the reference group (high 11dhTxB2 and low 8-IsoPGF2 alpha(adj): hazard ratio: 3.2, 95% confidence interval: 1.6-6.6, P=0.002; high 11dhTxB(2) and 8-IsoPGF(2)alpha(adj): 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. Conclusion We found that 11dhTxB(2) appears to be a better prognostic marker for mortality as compared with 8-IsoPGF2 alpha, suggesting aspirin resistance itself is a stronger independent determinant of death in CAD patients treated with aspirin. Coron Artery Dis 28: 287-293 Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.