Urinary 11-Dehydro-Thromboxane B 2 and Mortality in Patients With Stable Coronary Artery Disease

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

doi:10.1016/j.amjcard.2016.12.004

Cited by 21 publications

(20 citation statements)

References 21 publications

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Section: Discussionmentioning

confidence: 99%

“…Studies have emerged in recent years demonstrating that persistent TXA 2 generation in patients with cardiovascular disease undergoing aspirin therapy predicts an increased risk of atherothrombosis and death. 4,7,8 Although initially assumed to be attributable to the failure of aspirin to inhibit platelet COX-1-mediated thromboxane generation and consequent platelet activation, it is now recognized that aspirin is efficient at inhibiting platelet COX-1 and that much of the residual TXA 2 generation in patients taking aspirin originates from nonplatelet sources. [26][27][28] A unique feature of our analysis was that it only included subjects in whom inhibition of platelet thromboxane generation was verified, conclusively demonstrating that TXA 2 originating from nonplatelet tissue adversely affects clinical outcome and survival.…”

Section: Discussionmentioning

confidence: 99%

“…3 A substantial percentage of patients with cardiovascular disease continue to generate significant amounts of TXA 2 despite aspirin therapy, which places them at risk for adverse cardiovascular events. [4][5][6][7][8] Although initially thought to represent a failure of aspirin to inhibit platelet TXA 2 generation, emerging evidence suggests that residual TXA 2 generation derives principally from nonplatelet sources not suppressible by once-daily dosing regimens. 6,[9][10][11][12][13] In the RIGOR (Reduction in Graft Occlusion Rates) study, nonplatelet TXA 2 generation was identified as a novel risk factor for saphenous vein graft thrombotic occlusion after first-time coronary artery bypass graft (CABG) surgery.…”

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confidence: 99%

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Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

Kakouros

Gluckman²,

Conte³

et al. 2017

JAHA

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BackgroundSystemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long‐term clinical outcome.Methods and ResultsFive‐year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11‐dehydrothromboxane B2 (11‐dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11‐dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11‐dhTXB2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P=0.02) and death (adjusted hazard ratio, 2.90; P=0.01) at 5 years compared with lower values. Additional modeling revealed 11‐dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11‐dhTXB2 measured 6 months later, which highly associated with oxidative stress.ConclusionsLong‐term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5‐year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long‐term clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

Kakouros

Gluckman²,

Conte³

et al. 2017

JAHA

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“…Aspirin is a widely used antiplatelet drug that is recommended by numerous medical guidelines to be used in the treatment of cardiovascular and cerebrovascular diseases (CCVDs). Studies have shown that aspirin‐based antiplatelet therapy reduces the incidence of stroke and myocardial infarction, and cardiovascular‐related deaths in patients with coronary heart disease . Aspirin is a non‐steroidal anti‐inflammatory agent with antithrombotic effects mediated through cyclooxygenase‐1 (COX‐1) inhibition.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Aspirin resistance mediated by oxidative stress‐induced 8‐Isoprostaglandin F2

2019

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Summary What is Known and Objective Aspirin resistance refers to a patient's poor response to aspirin. There are many factors that can contribute to aspirin resistance, including single‐nucleotide polymorphisms, medication compliance, drug‐drug interactions and inflammation. Comment Recently, oxidative stress‐induced 8‐isoprostaglandin F2α has attracted considerable attention because it is considered as a mechanism of aspirin resistance in many diseases, including coronary artery disease, neurology system disease, metabolic syndrome, cancer, chronic obstructive pulmonary disease and chronic kidney disease. In these diseases, increased oxidative stress may promote platelet activation and reduce the efficacy of aspirin by producing excessive amounts of 8‐isoprostaglandin F2α. What is New and Conclusion Given the wide clinical use of aspirin, it is essential to understand why some patients do not response to it. This article reviews current research on aspirin resistance mediated by oxidative stress‐induced 8‐isoprostaglandin F2α.

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“…Aspirin is a widely used antiplatelet agent because low-dose aspirin can effectively block the platelet cyclooxygenase-1 (COX-1) activity and inhibit the synthesis of thromboxane A2 (TXA2) (Chen & Chou, 2018;Lopez et al, 2014;McCullough et al, 2017), which plays an essential anti-thrombotic role in patients with ischemic stroke. Aspirin resistance refers to the poor responsiveness of some patients to aspirin therapy, which is often described as a failure of aspirin to meet its expected biological effectiveness such as platelet inhibition or an aspirin failure to prevent atherosclerotic thrombus events (Al-Jabi Samah, 2017;Mason Peter, Jacobs Alice, & Freedman, 2005).…”

Section: Introductionmentioning

confidence: 99%

Association of aspirin resistance with 4‐hydroxynonenal and its impact on recurrent cerebral infarction in patients with acute cerebral infarction

et al. 2020

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Objectives To investigate the association of aspirin resistance (AR) with the plasma 4‐hydroxynonenal (4‐HNE) level and its impact on recurrent cerebral infarction (CI) in patients with acute cerebral infarction (ACI) who were receiving aspirin therapy. Methods One hundred and fifty‐four ACI patients who previously received aspirin therapy (100 mg/day) were enrolled. Whole urine (for measuring 11dhTXB2 and creatinine) along with blood (for measuring the plasma 4‐HNE level) were collected at least 7 days after the patients received aspirin. A cutoff of 1500 pg/mg of 11dhTXB2/ creatinine was used to determine AR. A follow‐up period to monitor recurrence CI events was 1 year. In addition, blood testing was performed when the patients were first admitted to hospital. Results Forty‐six of the 154 enrolled patients (29.9%) were found to be AR. No statistical difference in age, sex, hypertension, diabetes mellitus, coronary disease, smoking status, NIHSS score, TOAST classification, platelet count, thrombocytocrit, LDL‐C, HDL‐C, TG, and TC was found between the AR and aspirin‐sensitive (AS) patients, but the plasma 4‐HNE level was found to be higher in the AR patients than AS patients (p < .05). Multiple logistic regression analysis showed that the 4‐HNE level was associated with a higher risk of AR (OR = 1.034; 95% CI = 1.011–1.058; p < .05). Moreover, 1‐year follow‐up showed that AR was more prevalent in patients with recurrent CI (26 (56.6%)) than those without (20/(43.5%)) (p < .001). Conclusions The plasma 4‐HNE level is strongly associated with AR and thus may be a factor contributing to AR. Patients with AR have a greater risk of recurrence CI.

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Urinary 11-Dehydro-Thromboxane B 2 and Mortality in Patients With Stable Coronary Artery Disease

Cited by 21 publications

References 21 publications

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

Aspirin resistance mediated by oxidative stress‐induced 8‐Isoprostaglandin F2

Association of aspirin resistance with 4‐hydroxynonenal and its impact on recurrent cerebral infarction in patients with acute cerebral infarction

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