Eric J Heyer, Joanna L Mergeche, Samuel S Bruce, E Sander Connolly
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.
我们之前的研究表明，无症状颈动脉内膜切除术(CEA)患者术前服用他汀类药物时，围手术期神经损伤较少，神经损伤定义为卒中和早期认知功能障碍(eCD)在CEA后24小时内观察到。本研究探讨无症状CEA后24小时观察到的eCD发生率是否随他汀类药物类型或剂量的变化而变化。计划进行CEA的无症状颈动脉狭窄患者同意参加一项经irb批准的观察性研究(N=324)。术前和术后24小时对患者进行广泛的神经心理测试。在324名同意的患者中，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无eCD，而服用洛伐他汀(17.7%)和瑞舒伐他汀(16.7%)的患者eCD发生率与未服用他汀的患者相似(20.2%)。服用辛伐他汀的患者eCD发生率明显低于服用阿托伐他汀的患者(3.0% vs. 16.0%， P=0.005)。服用最大剂量他汀类药物的患者的eCD发生率明显低于服用次最大剂量的患者(2.7% vs. 15.9%， P=0.002)。这些观察结果表明，eCD的发生率实际上可能随他汀类药物类型的不同而变化，最大剂量可能是CEA患者的最佳剂量。这种变化可能是由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。这些发现应用于激励随机前瞻性工作，以确定CEA前优化他汀类药物使用的安全性、可行性和结果。
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