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Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease
Peter A McCullough1, Anupama Vasudevan2, Mohanakrishnan Sathyamoorthy3
1Baylor University Medical Center, Dallas, Texas; Baylor Heart and Vascular Institute, Dallas, Texas; Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas; The Heart Hospital Baylor Plano, Plano, Texas; Texas A&M Health Science Center College of Medicine, Dallas Campus, Dallas, Texas.
Insights
Urinary 11-dehydro-thromboxane B2 (11dhTxB2) levels indicate increased mortality risk in coronary artery disease (CAD) patients on aspirin. Higher 11dhTxB2 concentrations signal a need for intensified secondary prevention strategies.
Area of Science:
- Cardiology
- Biomarkers
- Pharmacology
Background:
- Aspirin therapy is standard for reducing adverse events in coronary artery disease (CAD).
- Aspirin's effectiveness relies on inhibiting cyclooxygenase-1 (COX-1) and thromboxane A2 (TXA2)-mediated platelet aggregation.
- Variable COX-1 suppression by aspirin necessitates identifying alternative risk markers.
Purpose of the Study:
- To investigate the association between urinary 11-dehydro-thromboxane B2 (11dhTxB2) levels and mortality in stable CAD patients on aspirin.
- To determine if 11dhTxB2 serves as an independent predictor of all-cause mortality in this population.
Main Methods:
- Chart abstraction and measurement of urinary 11dhTxB2 from frozen samples in a cohort of stable CAD patients.
- Analysis of demographic data, comorbidities, and mortality outcomes over a median follow-up of 1,149 days.
- Cox proportional hazards analysis to assess the risk of mortality associated with 11dhTxB2 tertiles, adjusting for covariates.
Main Results:
- Higher urinary 11dhTxB2 levels correlated with increased age, and were more prevalent in women, and patients with COPD and heart failure.
- A significant trend for increased all-cause mortality was observed across increasing tertiles of 11dhTxB2.
- Patients in the middle and upper 11dhTxB2 tertiles exhibited significantly higher risks for mortality (HR 7.14 and 9.91, respectively) after adjustment.
Conclusions:
- Urinary 11dhTxB2 concentration is a potent independent risk factor for all-cause mortality in stable CAD patients receiving aspirin.
- Elevated 11dhTxB2 may identify patients requiring more aggressive secondary prevention measures.
- This biomarker could refine risk stratification and guide treatment intensification in CAD management.
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.
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