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

McCullough, Peter A.; Vasudevan, Anupama; Lopez, Luis R.; Swift, Caren; Peterson, Margarita; Bennett-Firmin, Jeanna; Schiffmann, Raphael

doi:10.1016/j.thromres.2016.10.022

Cited by 11 publications

(10 citation statements)

References 12 publications

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“…In a prior analysis of this study cohort, oxidative stress, as measured by urine 8‐iso‐prostaglandin 2α, was identified as the strongest variable associated with urine 11‐dhTXB 2 , measured 6 months after surgery, accounting for approximately half of the modeled effect and consistent with data from other study populations . Age, race, statin use, and aspirin dose were also associated, but to lesser degrees.…”

Section: Resultssupporting

confidence: 73%

“…In a prior analysis of this study cohort, 13 oxidative stress, as measured by urine 8-iso-prostaglandin 2a, was identified as the strongest variable associated with urine 11-dhTXB 2 , measured 6 months after surgery, accounting for approximately half of the modeled effect and consistent with data from other study populations. 20,21 Age, race, statin use, and aspirin dose were also associated, but to lesser degrees. Given the observed differences in subject characteristics associated with high 11-dhTXB 2 levels when measured at (Table 1), we sought to understand if stimuli for nonplatelet TXA 2 generation during the early perioperative period, when subjects were under acute physiologic stress, differed from those 6 months later, when subjects would more likely to be at their physiologic baseline.…”

Section: Variables Associated With Nonplatelet Txa 2 Generation Earlymentioning

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: Resultssupporting

confidence: 73%

Section: Variables Associated With Nonplatelet Txa 2 Generation Earlymentioning

confidence: 99%

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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“…8‐isoprostaglandin F2α is a thromboxane platelet receptor (TP receptor) agonist. By its binding to TP receptors in platelets and vessels, 8‐isoprostaglandin F2α leads to vasoconstriction and platelet activation, just as TXA2 does . Specifically, 8‐isoprostaglandin F2α, an isoprostaglandin, binds to TP receptors to induce vasoconstriction by promoting the release of endogenous Ca 2+ and activating the RhoA/Rho kinase 1 and 2 signalling pathways and to mediate platelet activation by promoting ADP‐dependent platelet aggregation .…”

Section: Commentmentioning

confidence: 99%

“…The elevated level of 8‐isoprostaglandin F2α suggests that its formation is not affected by aspirin therapy, but rather is due to disrupting lipoproteins by reactive oxygen species. Consequently, an increasing in the level of 8‐isoprostaglandin F2α promotes platelet activation . Another study involving 55 CAD patients found that both 8‐isoprostaglandin F2α and peroxide in plasma were associated with oxidative stress, and they are closely related to aspirin resistance .…”

Section: Commentmentioning

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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“…It is noted that although aspirin reduces the production of TXA2 by inhibiting COX, it has different inhibitory effects on COX‐1 and COX‐2. Aspirin inhibits COX‐1 effectively, but has weak effect on COX‐2 (McCullough et al, ).…”

Section: Discussionmentioning

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

Cited by 11 publications

References 12 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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