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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.

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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The Current and Future Landscape of Urinary Thromboxane Testing to Evaluate Atherothrombotic Risk


"Biomarker testing for efficacy of therapy is an accepted way for clinicians to individualize dosing to genetic and/or environmental factors that may be influencing a treatment regimen.  Aspirin is used by nearly 43 million Americans on a regular basis to reduce risks associated with various artherothrombotic diseases.  Despite its widespread use, many clinicians are unaware of the link between suboptimal response to aspirin therapy and increased risk for inferior clinical outcomes in several disease states, and biomarker testing for efficacy of aspirin therapy is not performed as routinely as efficacy testing in other therapeutic areas.  This article reviews the clinical and laboratory aspects of determining whole-body thromboxane production, particularly as it pertains to efficacy assessment of aspirin responsiveness."

"Aspirin use has been shown to cause a dose-dependent reduction in urinary levels of 11-dehydroTxB2."

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Measurements of thromboxane production and their clinical significance in coronary heart disease.

"Residual TX production, as revealed by different methods, may derive from COX-1 or COX-2.”

"Extra-platelet sources may contribute to aspirin-insensitive TX generation: monocytes/macrophages and vascular endothelial cells express COX-2 in response to inflammatory stimuli, and the up regulation of COX-2 activity may account for a TX biosynthesis not sensitive to once daily low-dose aspirin."

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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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Nutraceuticals in diabetes and metabolic syndrome

"Metabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes.  Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low-grade inflammation, alterred oxidative/antioxidant status, and persistent platelet activation."

"We examined the effects of short-term vitamin E supplementation (600 mg daily for 2 week) on the urinary excretion of 8-iso-PGF2alpha and 11-dehydro-TXB2. Vitamin E supplementation was associated with detectable changes in plasma vitamin E levels and caused virtually complete normalization of 8-iso-PGF2alpha excretion. Moreover, changes in F2-isoprostane formation were accompanied by similar reductions in thromboxane metabolite excretion."

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Natural sources of resveratrol and mechanisms of action with emphasis on cardiovascular disease: a brief review

“Epidemiological studies indicate that the consumption of red wine reduces the mortality and morbidity from CAD. Muscadine grapes contain high levels of antioxidants, including resveratrol, a polyphenol with multiple cardioprotective effects.” 

"These antioxidants are thought to be the effective agents behind the so-called "French Paradox," the low mortality rate from CAD amongs the French population desipite their high-fat diet and smoking."

"Resveratrol has been shown to inhibit lipid peroxidation of LDL, prevent the cytoxicity of oxidized LDL, protect cells against lipid peroxidation, reduce platelet aggregation, and inhibit vascular SMC proliferation".

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Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic Acid Determinants and Effect on Cardiovascular Risk

"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 thare 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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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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Molecular targets of tea polyphenols in the cardiovascular system

"Tea-derived polyphenols have attracted considerable attention in the prevention of cancer and cardiovascular diseases.  In comparison to tumour cells, the elucidation of their molecular targets in cardiovascular relevant cells is still at the beginning.  Although promising, experimental and clinical data demonstrate protective effects for the cardiovasclar system, little information is actually available on how these beneficial effects of tea polyphenols are mediated at the cellular level.  By affecting the activity of receptor and signal transduction kinases, both catechins and theaflavins - the major ingredients of green and black tea, respectively - exert a variety of cardiovascular beneficial effects."

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Olive oil and hemostasis: a review on its healthy effects

"Interest in the Mediterranean diet (MD) has grown worldwide in the course of the past decade, even among nutritionists outside of the Mediterranean area.  This is largely due to the fact that the consumption of the MD has been linked to greater longevity, improved quality of life and lower incidences of cardiovascular disease, cancer and age cognitive decline, in spite of being a dietary model with a high fat content, unlike the diets recommended for several decades by many experts in nutrition in other geographical areas."  

“A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and thromboxane B2 plasma levels."

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