Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis
Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis
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DOI：
10.1111/j.1528-1167.2011.03316.x
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发表时间：
2012-01-01
期刊：
影响因子：
5.6
通讯作者：
Chan, Samuel H. H.
中科院分区：
文献类型：
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作者：
Chuang, Yao-Chung;Chuang, Hung-Yi;Chan, Samuel H. H.
目的：抗癫痫药物（AEDs）的长期治疗与导致癫痫患者动脉粥样硬化风险增加的代谢后果相关。我们比较了使用不同种类的AED单药治疗对血管风险标志物和动脉粥样硬化进程的长期影响。方法：160例接受AED单药治疗的成年患者，包括两种酶诱导剂。（卡马西平，CBZ;和苯妥英，PHT），酶抑制剂本研究纳入了60名对照组患者，其中60名患者接受丙戊酸（VPA）和非诱导剂（拉莫三嗪，LTG）治疗超过2年。所有研究参与者均接受B型超声测量颈总动脉（CCA）内膜中层厚度（IMT）以评估动脉粥样硬化的程度。其他测量包括体重指数，血脂或总同型半胱氨酸（tHcy），叶酸，尿酸，空腹血糖，高敏C-反应蛋白（hs-CRP），或硫代巴比妥酸反应物质（TBARS）的水平。关键发现：长期单药治疗与老一代抗癫痫药物，包括CBZ，PHT，丙戊酸盐，导致显着增加CCA IMT癫痫患者。校正年龄和性别的混杂效应后，CCA IMT与AED治疗时间呈正相关。服用酶诱导AED单药治疗（CBZ、PHT）的癫痫患者表现出胆固醇、tHcy或叶酸代谢紊乱，以及炎症标志物hs-CRP升高。另一方面，酶抑制性AED单药治疗（VPA）的患者显示尿酸和tHcy水平升高，氧化标志物TBARS升高。然而，没有显着改变的血管风险或CCA IMT的标志物中观察到的患者接受长期LTG单药治疗。意义：癫痫患者接受长期单药治疗与CBZ，PHT，或VPA表现出改变的循环标志物的血管风险，可能有助于加速动脉粥样硬化的过程中，这是显着相关的AED单药治疗的持续时间。这些信息为需要长期AED治疗的癫痫患者，特别是老年人和高危人群的药物选择提供了指导。
Purpose: Long-term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long-term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process.Methods: One hundred sixty adult patients who were receiving AED monotherapy, including two enzymeinducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme-inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C-reactive protein (hs-CRP), or thiobarbituric acid reactive substances (TBARS).Key Findings: Long-term monotherapy with older-generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme-inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs-CRP. On the other hand, patients on enzymeinhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long-term LTG monotherapy.Significance: Patients with epilepsy who were receiving long-term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require longterm AED therapy, particularly in aged and high-risk individuals.