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

Anupama Vasudevan, Teodoro Bottiglieri, Kristen M. Tecson, Mohanakrishnan Sathyamoorthy, Jeffrey M. Schussler, Carlos E. Velasco, Luis R. Lopez, Caren Swift, Margarita Peterson, Jeanna Bennett-Firmin, Raphael Schiffmann, Peter A. McCullough

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)287-293
Number of pages7
JournalCoronary Artery Disease
Volume28
Issue number4
DOIs
StatePublished - Jan 1 2017

Keywords

  • 11-dehydrothromboxane B
  • 8-iso-prostaglandin-F2α
  • aspirin
  • coronary artery disease
  • mortality
  • oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Vasudevan, A., Bottiglieri, T., Tecson, K. M., Sathyamoorthy, M., Schussler, J. M., Velasco, C. E., Lopez, L. R., Swift, C., Peterson, M., Bennett-Firmin, J., Schiffmann, R., & McCullough, P. A. (2017). Residual thromboxane activity and oxidative stress: Influence on mortality in patients with stable coronary artery disease. Coronary Artery Disease, 28(4), 287-293. https://doi.org/10.1097/MCA.0000000000000461