Platelet reactivity to adenosine diphosphate and CYP2C19 genotypes are linked with carotid plaques and may predict carotid plaque stability in acute ischemic stroke patients

血小板对二磷酸腺苷的反应性和CYP2C19基因型与颈动脉斑块相关,并可能预测急性缺血性卒中患者的颈动脉斑块稳定性。

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Abstract

OBJECTIVES: To determine the correlations of ADP-induced platelet-inhibition rate (ADP-PIR) and CYP2C19 genotypes with carotid plaque types in acute ischemic stroke (AIS). Unstable carotid plaques are implicated in AIS. Clopidogrel (commonly prescribed in AIS) produces adenosine diphosphate (ADP)-induced platelet inhibition, and is metabolized by CYP2C19. METHODS: We retrospectively evaluated the data of AIS patients treated at our hospital during 2019-2022, and administered maintenance clopidogrel (75 mg/d). Carotid plaques, ADP-PIR, and CYP2C19 genotypes were assessed using color Doppler ultrasonography, thromboelastography, and polymerase chain reaction assays, respectively. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were conducted. RESULTS: Of 692 study patients, 378 (54.6%) and 128 (18.5%) had unstable and stable carotid plaques, respectively. Multivariate logistic regression identified PIR and CYP2C19 genotype as independent risk factors for stable carotid plaque (PIR, OR: 0.984, 95% CI: 0.974-0.995, p=0.003; intermediate metabolizer, OR: 0.158, 95% CI: 0.066-0.379, p<0.001; poor metabolizer, OR: 0.584, 95% CI: 0.155-2.206, p=0.428) and unstable carotid plaque (PIR, OR: 0.957, 95% CI: 0.949-0.966, p<0.001; intermediate metabolizer, OR: 0.151, 95% CI: 0.063-0.362, p<0.001; poor metabolizer, OR: 0.145, 95% CI: 0.051-0.416, p<0.001). Areas under the ROC curve for predicting unstable and stable carotid plaques were 0.700 (PIR) and 0.716 (CYP2C19 genotype), and 0.631 (PIR) and 0.650 (CYP2C19 genotype), respectively. CONCLUSION: The PIR and CYP2C19 genotype are correlated with and may predict carotid plaque types in AIS.

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