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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.

Mediterranean diet reduces thromboxane A2 production in atrial fibrillation patients

"Platelet activation plays a major role in cardiovascular events.  Mediterranean diet reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation.  Aim of the study was to evaluate the effect of Mediterranean diet on the urinary excretion of 11-dehydro-thromboxane (TX) B2, a marker in vivo platelet activation, in patients with atrial fibillation."

"Med diet adherence is inversely associated to urinary excretion of 11-dehydro-TXB2, suggesting that Med-Diet may favorably affect platelet function in AF 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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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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Statin therapy and inflammation in patients with diabetes treated with high dose aspirin

"Statin and aspirin form the therapeutic cornerstone in patients with coronary artery disease and diabetes.  Little is known about relationship of statins with blood thrombogenicity and inflammation in these patients."

"Statins along with aspirin, confers additional anti-inflammatory and antithrombotic effect in diabetics with CAD. Urinary 11-DHTXB2 may be a useful biomarker for personalizing statin therapy."

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Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible factors Predisposing to Sub-optimal Platelet Response to Aspirin?

"Both environmental and genetic factors, including aspirin pharmacokinetics, inflammation, platelet COX-2, use of non-steroid anti-ainflammatory drugs and dyslipidaemia may determine variable platelet response to acetylsalicylic acid.”’ 

"However, CRP level was significantly associated with the extent of platelet refractoriness to acetylsalicylic acid in these patients, which points out that even subclinical inflammatory states may be considered possible candidates for suboptimal acetylsalicylic acid response."

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Relation of fish oil supplementation to markers of atherothrombotic risk in patients with cardiovascular disease not receiving lipid-lowering therapy.

"Fish oil supplementation (FOS) is known to have cardiovascular benefits.  However, the effects of FOS on thrombosis are incompletely understood.  We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease."

"Fish oil supplementation (FOS) is known to have cardiovascular benefits. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy."

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The improvement of walking abilities and endothelial function after the supervised training treadmill program

"In this prospective study we evaluated the relationship between thromboxane B2 (TXB2), prostacyclin (PGI2) and lactate concentrations, and the improvement of walking abilities and endothelial function in patients with peripheral artery disease (PAD) undergoing a supervised treadmill training program (STTP)."

The Maximal Walking Time (MWT) improved significantly after STTP by 91% (p<0.0001) and PFWT by 97% (P<0.0001).  Also ankle/brachial index (ABI) values improved significantly after STTP in all patient groups and was more pronounced in those with longer MWT at baseline.  FMD values increased by 45% (p<0.0001) after STTP.  Urinary 11-dehydro-thromboxane B2 and 2, 3-dinor-6-keto-PGF1a concentration tend to decrease after STTP and their ratio remained unchanged.  Lactate levels did not change after the treadmill training program.  Hs-CRP and fibrinogen concentration decreased signficantly after STTP only in patients with longer MWT at baseline - fourth quartile".

"STTP in patients with PAD showed signficantly improved walking abilities and endothelialial function."

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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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The influence of low-grade inflammation on platelets in patients with stable coronary artery disease.

"Inflammation is likely to be involved in all stages of atherosclerosis.  Numerous inflammatory biomarkers are currently being studied, and even subtle increases in inflammatory biomarkers have been associated with increased risk of cardiovascular events in patients with coronary artery disease (CAD).  Low-grade inflammation may influence both platelet production and platelet activation potentially leading to enhanced platelet aggregation."

"Increased levels of hsCRP and IL-6 were independently associated with increased platelet aggregation and urine-11-dehydrothromboxane B2 levels (110). This association may be explained by aspirin-insensitive thromboxane generation derived from cyclooxygenase-2 in non-platelet cells."

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Oxidative stress reflected by increased F2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane B2 levels in patients with coronary artery disease.2016

"Oxidative stress is a potential mechanism of incomplete inhibition of COX-1.

"8-isoPGF2a was found to be independently and positively associated with 11 dhTxB2."

"Elevated 11dhTxB2 was found to increase the risk of adverse events in patients with stable CAD [12] and myocardial infarction."

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