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

Juan Guo,Jue Wang,Juan Feng,Yanxia Guo

doi:10.1002/brb3.1562

Abstract

ObjectivesTo 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.MethodsOne 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.ResultsForty‐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).ConclusionsThe 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.

Highlights

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)
Our analysis showed that an increase in the incidence of aspirin resistance was associated with age (OR = 1.040, [95%cerebral infarction (CI) 1.003–1.079], p = .034), but no association was found between the parameters such as sex, hypertension, diabetes mellitus, and coronary disease were not associated and the incidence of aspirin resistance

Summary

| INTRODUCTION

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. Studies have shown that 4-HNE is a biomarker of oxidative stress and plays an important role in the pathophysiological process of many diseases (Neven, 2003; Zelzer et al, 2015), including ischemic stroke, neurodegenerative diseases, coronary heart disease, cancer, metabolic syndrome, acute lung injury, and others (Castro, Jung, Grune, & Siems, 2017; Lee et al, 2012; Mason, Charishma, Richard, & Kolliputi, 2016; Xiao, Zhong, Xia, Tao, & Yin, 2017). It was further suggested that the level of plasma 4-HNE might be a biomarker of ischemic stroke as it is closely related to oxidative stress and lipid peroxidation (Lee et al, 2012). Guo et al suggest that oxidative stress is an important factor leading to ischemic damage, and they found that reactive aldehydes like malonaldehyde (MDA) and 4-HNE produced by oxidized lipids could be detected in all ischemic tissues, including brain tissue, suggesting that the elevated plasma 4-HNE level may be one of the risk factors of cerebral apoplexy (Guo et al, 2013).

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Findings

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