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Cardiovascular Disease

The thromboxane A2 pathway and its components are implicated in the progression of atherosclerosis and cardiovascular diseases. (CAD) Thromboxane A2 is clearly involved in CAD due to its acute and chronic role in promotion of vasoconstriction and platelet aggregation. The success of low-dose aspirin in prevention of CAD is explained by platelet COX-1 inhibiting thromboxane A2 biosynthesis. Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway that regulate thromboxane A2 generation.

11-Dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period.

"Overall the mean TXB2 values immediately after PTA were significantly higher than either before the procedure (1524.4 pg/mg ± 1411.1 vs. 2098.1 pg/mg creatinine ± 1661.8; P=0.00002), the day after PTA, or at any other point during the study.”

"Moreover, preoperative TXB2 levels correlated well with the composite endpoints of death, myocardial infarction and stroke during the follow-up period"

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Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

"Cardiovascular events (CVEs) represent the main cause of morbidity and mortality in the elderly population.  Several mechanisms have been proposed so far to explain the age-related incidence of CVs.  Thus, the prevalence of cardiovascular risk factors, such as smoking, hypertension and diabetes increases in elderly people.  Of note is that despite increasingly effective cardiovascular preventive strategies a portion of patients still experience cardiovascular complications."

"Urinary excretion of 11-dehydro-txb2 increases by advancing age, peaking after 70 years."

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Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events.

"In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity."

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Risk factors for nonplatelet thromboxane generation after coronary artery bypass graft surgery.

"A significant finding of our analysis was that U8-iso-PGF2a correlated directly with the incidence of early vein graft thrombosis. This suggests that therapies aimed at reducing oxidative stress might be a viable strategy to reduce nonplatelet TXA2 generation and improve outcomes after cardiac surgery."

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Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid

"Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydrothromboxane B2 concentrations, has been associated with an increased risk of cardiovascular events.  We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B2 concentrations that could thereby reduce cardiovascular risk."

"In aspirin-treated patients, urinary concentrations of 11-dehydrothromboxane B2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction or cardiovascular death in patients at risk for atherothrombotic events."

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Urinary 11-dehydro-thromboxane B2 is associated with cardiovascular events and mortality in patients with atrial fibrillation

"Patients with nonvalvular atrial fibrillation (AF) show high residual cardiovascular (CV) risk despite oral anticoagulants.  Urinary 11-dehydro-thromboxane B2 (TXB2) is associated with an increased risk of CV events (CVEs), but its predictive value in patients with anticoagulated AF is unknown."

"Urinary 11-dehydro-TxB2 levels are associated with a residual risk of CVEs and CV mortality in patients with AF despite anticoagulant treatment."

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Urinary 11-dehydro-thromboxane B2 and mortality in patients with stable coronary artery disease

"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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Sex differences in urinary biomarkers of vascular and endothelial function in HIV-infected persons receiving antiretroviral therapy

"Cardiovascular disease (CVD) risk can be underestimated in HIV-infected patients receiving antiretroviral therapy (ART). Novel CVD risk markers in this population are needed.  We hypothesized that eicosanoid metabolite production is increased with metabolic complications of ART.  Our objective was to determine relationships between urine eicosanoids and traditional CVD risk factors in a cohort of HIV-infected persons receiving ART."

"In this pilot study of predominantly virologically suppressed HIV-infected individuals on ART, there were sex-specific differences in urinary eicosanoids, with females having more risk-associated parameters despite low Framingham score.  Eicosanoids might be useful CVD biomarkers in ART-treated, HIV-infected patients."

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