Department of Neurology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
Epilepsia. 2013 Oct;54(10):e146-9. doi: 10.1111/epi.12338. Epub 2013 Aug 23.
Although it is well documented that long-term therapy with older antiepileptic drugs (AEDs) leads to an increase in risk for atherosclerosis, there has been only limited information regarding the vascular risk in patients who are treated with new AEDs. We therefore conducted a prospective longitudinal study to assess the potential effects of new AEDs on the circulatory markers for vascular risk in patients with newly diagnosed epilepsy. We recruited adult patients with epilepsy who began to receive monotherapy with one of the new AEDs, including levetiracetam (LEV), oxcarbazepine (OXC), and topiramate (TPM). Circulatory markers of vascular risk were measured twice before and after 6 months of AED monotherapy. A total of 109 patients completed the study (LEV, n = 40; OXC, n = 40; TPM, n = 29). Six months of monotherapy resulted in significant increases in low-density lipoprotein cholesterol (LEV, from 90.2 to 98.5 mg/dl, 9.2% increase, p = 0.025; OXC, from 96.5 to 103.2 mg/dl, 7.0% increase, p = 0.049), homocysteine (LEV, from 7.9 to 10.4 μm, 31.6% increase, p = 0.001; OXC, from 8.7 to 11.5 μm, 32.2% increase, p < 0.001; TPM, from 8.3 to 12.3 μm, 48.2% increase, p < 0.001), apolipoprotein B (LEV, from 63.6 to 77.4 mg/dl, 21.7% increase; OXC, from 67.0 to 83.2 mg/dl, 24.2% increase; TPM, from 66.7 to 84.4 mg/dl, 26.5% increase; all p < 0.001), and apolipoprotein B/apolipoprotein A1 ratio (LEV, from 0.51 to 0.61, 19.6% increase; OXC, from 0.52 to 0.67, 28.8% increase; TPM, from 0.50 to 0.67, 34.0% increase; all p < 0.001). Serum apolipoprotein A1 and folate were significantly decreased in TPM (from 139.1 to 132.1 mg/dl, 5.0% decrease, p = 0.014) and OXC (from 8.1 to 6.4 ng/ml, 21.0% decrease, p = 0.046) groups, respectively. There were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, lipoprotein(a), and vitamin B12 in all three groups. Our findings suggest that treatment with some new AEDs might be associated with alterations in circulatory markers of vascular risk, which could contribute to the acceleration of atherosclerosis and increased risk of vascular diseases.
虽然已有大量文献证实，长期使用较老的抗癫痫药物（AED）会增加动脉粥样硬化的风险，但有关新 AED 治疗患者的血管风险方面的信息却十分有限。因此，我们进行了一项前瞻性纵向研究，以评估新 AED 对新诊断为癫痫的患者循环血管风险标志物的潜在影响。我们招募了开始接受新型 AED 单药治疗的成年癫痫患者，包括左乙拉西坦（LEV）、奥卡西平（OXC）和托吡酯（TPM）。在 AED 单药治疗前和治疗 6 个月后两次测量循环血管风险标志物。共有 109 名患者完成了研究（LEV，n = 40；OXC，n = 40；TPM，n = 29）。单药治疗 6 个月后，低密度脂蛋白胆固醇（LEV，从 90.2 升至 98.5mg/dl，增加 9.2%，p = 0.025；OXC，从 96.5 升至 103.2mg/dl，增加 7.0%，p = 0.049）、同型半胱氨酸（LEV，从 7.9 升至 10.4μm，增加 31.6%，p = 0.001；OXC，从 8.7 升至 11.5μm，增加 32.2%，p < 0.001；TPM，从 8.3 升至 12.3μm，增加 48.2%，p < 0.001）、载脂蛋白 B（LEV，从 63.6 升至 77.4mg/dl，增加 21.7%；OXC，从 67.0 升至 83.2mg/dl，增加 24.2%；TPM，从 66.7 升至 84.4mg/dl，增加 26.5%；均 p < 0.001）和载脂蛋白 B/载脂蛋白 A1 比值（LEV，从 0.51 升至 0.61，增加 19.6%；OXC，从 0.52 升至 0.67，增加 28.8%；TPM，从 0.50 升至 0.67，增加 34.0%；均 p < 0.001）显著增加。TPM（从 139.1 降至 132.1mg/dl，降低 5.0%，p = 0.014）和 OXC（从 8.1 降至 6.4ng/ml，降低 21.0%，p = 0.046）组的血清载脂蛋白 A1 和叶酸显著降低。三组患者的总胆固醇、甘油三酯、高密度脂蛋白胆固醇、脂蛋白（a）和维生素 B12 均无显著变化。我们的研究结果表明，一些新型 AED 的治疗可能与循环血管风险标志物的改变有关，这可能导致动脉粥样硬化加速和血管疾病风险增加。
