Key result
In patients with stable CAD, 11dhTxB2 levels above the median were associated with a significantly higher risk of all-cause mortality compared to levels below the median (HR 3.2; 95% CI 1.6-6.6; P=0.002).
Why the study?
Does elevated urinary 11dhTxB2 or 8-IsoPGF2α predict all-cause mortality in patients with stable CAD treated with aspirin?
Cohort (n=447)
Does elevated urinary 11dhTxB2 or 8-IsoPGF2α predict all-cause mortality in patients with stable CAD treated with aspirin?
Hazard Ratio: 3.2 (95% CI 1.6–6.6)
p-value: p=0.002
Elevated urinary 11dhTxB2 is a strong independent predictor of all-cause mortality in patients with stable CAD, suggesting aspirin resistance is a significant determinant of death.
High 11dhTxB2 signals excess mortality in aspirin-treated stable CAD; hypothesis-generating and requires prospective validation before clinical use.
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. CONCLUSION: 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.
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Vasudevan et al. (2016) conducted a cohort in stable coronary artery disease (CAD) (n=447). 11dhTxB2 levels above the median vs. 11dhTxB2 and 8-IsoPGF2α levels below their corresponding medians was evaluated on all-cause mortality (HR 3.2, 95% CI 1.6-6.6, p=0.002). In patients with stable CAD, 11dhTxB2 levels above the median were associated with a significantly higher risk of all-cause mortality compared to levels below the median (HR 3.2; 95% CI 1.6-6.6; P=0.002).
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