Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease

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

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)–mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (±SD) of 67 ± 10 and 65 ± 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2 (p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.

Original languageEnglish (US)
Pages (from-to)972-977
Number of pages6
JournalAmerican Journal of Cardiology
Volume119
Issue number7
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    McCullough, P. A., Vasudevan, A., Sathyamoorthy, M., Schussler, J. M., Velasco, C. E., Lopez, L. R., Swift, C., Peterson, M., Bennett-Firmin, J., Schiffmann, R., & Bottiglieri, T. (2017). Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease. American Journal of Cardiology, 119(7), 972-977. https://doi.org/10.1016/j.amjcard.2016.12.004