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颈动脉内膜切除术后的认知功能障碍是否因他汀类药物类型或剂量而异?

Does Cognitive Dysfunction after Carotid Endarterectomy Vary by Statin Type or Dose?

作者信息

Heyer Eric J, Mergeche Joanna L, Bruce Samuel S, Connolly E Sander

机构信息

Department of Anesthesiology, Columbia University, New York, 10032, United States of America ; Department of Neurology, Columbia University, New York, 10032, United States of America.

Department of Anesthesiology, Columbia University, New York, 10032, United States of America.

出版信息

Int J Brain Cogn Sci. 2013;2(4):57-62.

Abstract

Our previous work demonstrates that asymptomatic carotid endarterectomy (CEA) patients demonstrate less perioperative neurologic injury, defined as stroke and early cognitive dysfunction (eCD) observed within 24hr of CEA, when taking statins pre-operatively. This study examines whether the incidence of eCD observed 24hr after asymptomatic CEA varies as a function of statin type or dose. Patients with asymptomatic carotid stenosis scheduled for CEA consented to participate in an observational IRB-approved study (N=324). Patients were evaluated with an extensive battery of neuropsychometric tests pre-operatively and 24hr post-operatively. Of the 324 consented patients, 200 were taking statins. Patients taking pravastatin and fluvastatin exhibited no eCD, while patients taking lovastatin (17.7%) and rosuvastatin (16.7%) exhibited incidences of eCD similar to those not taking statins (20.2%). Patients taking simvastatin exhibited a significantly lower incidence of eCD than those taking atorvastatin (3.0% vs. 16.0%, P=0.005). Patients taking a maximal dose of any statin exhibited a significantly lower incidence of eCD than patients taking sub-maximal doses (2.7% vs. 15.9%, P=0.002). These observations suggest that the incidence of eCD may in fact vary as a function of statin type and that maximal doses may be the optimal dose for patients undergoing CEA. This variation may be due to the physico-chemical properties of statins such as lipophilicity, molecular size, and blood brain barrier penetrability. These findings should be used to inspire randomized prospective work to determine the safety, feasibility, and outcomes of optimizing statin use prior to CEA.

摘要

我们之前的研究表明,无症状颈动脉内膜切除术(CEA)患者在术前服用他汀类药物时,围手术期神经损伤较少,围手术期神经损伤定义为CEA术后24小时内发生的中风和早期认知功能障碍(eCD)。本研究旨在探讨无症状CEA术后24小时观察到的eCD发生率是否因他汀类药物类型或剂量而异。计划接受CEA的无症状颈动脉狭窄患者同意参与一项经机构审查委员会批准的观察性研究(N = 324)。患者在术前和术后24小时接受了一系列广泛的神经心理测试评估。在324名同意参与的患者中,200名正在服用他汀类药物。服用普伐他汀和氟伐他汀的患者未出现eCD,而服用洛伐他汀(17.7%)和瑞舒伐他汀(16.7%)的患者出现eCD的发生率与未服用他汀类药物的患者(20.2%)相似。服用辛伐他汀的患者eCD发生率显著低于服用阿托伐他汀的患者(3.0%对16.0%,P = 0.005)。服用任何他汀类药物最大剂量的患者eCD发生率显著低于服用次最大剂量的患者(2.7%对15.9%,P = 0.002)。这些观察结果表明,eCD的发生率实际上可能因他汀类药物类型而异,最大剂量可能是接受CEA患者的最佳剂量。这种差异可能归因于他汀类药物的物理化学性质,如亲脂性、分子大小和血脑屏障穿透性。这些发现应用于启发随机前瞻性研究,以确定CEA术前优化他汀类药物使用的安全性、可行性和结果。

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