Long‐term antiepileptic drug therapy contributes to the acceleration of atherosclerosis

Abstract

SUMMARYPurpose: Long-term antiepileptic drug (AED) therapy has been associated with an increase in risk of atherosclerosis. At issue is whether this risk is related to the duration of AED therapy. We evaluated the hypothesis that the cumulative effect of long-term exposure to AEDs plays a pivotal role in the pathogenesis of atherosclerosis in patients with epilepsy. Methods: One hundred ninety-five patients under long-term AED therapy and 195 healthy age-and sex-matched control subjects received measurement of intima media thickness (IMT) at the far wall of the common carotid artery (CCA) by Bmode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index (BMI) and blood lipid profile or homocysteine, folic acid, uric acid, fasting blood sugar, high sensitivity C-reactive protein (hs-CRP), thiobarbituric acid reactive substances (TBARS), and total reduced thiols.Results: CCA IMT was significantly increased in patients with epilepsy, with male subjects exhibiting thicker IMT than their female counterparts. Whereas BMI, homocysteine, hs-CRP, and TBARS were significantly elevated, folic acid and thiols were significantly reduced in patients with epilepsy. Multiple linear regression analysis further revealed that duration of AED therapy, age, gender, and TBARS level (index for oxidative stress) were independently associated with CCA IMT. In addition, the log-transformed CCA IMT increased linearly with duration of AED therapy after adjustments for age, gender, and TBARS level. Discussion: The duration of AED therapy is significantly associated with the acceleration of atherosclerosis in patients with epilepsy, alongside independent contributions of age, gender, and oxidative stress to the atherosclerotic process.

Early Atherosclerotic Changes in the Patients with Idiopathic Epilepsy: Egyptian Preliminary Study

“…This result was in agreement with other studies [14,17,20,21]. The antiepileptic drugs are thought to cause increase in the CCA IMT through alterations in lipid profile and lipoproteins [22,23].…”

Conversion from enzyme-inducing antiepileptic drugs to topiramate: Effects on lipids and c-reactive protein

“…CRP has recently been shown to be elevated in patients with epilepsy relative to controls (Tan et al, 2009), but our previous investigation, to our knowledge, is the only one that has examined this phenomenon in a drug-specific fashion (Mintzer et al, 2009). The current findings reinforce those of the previous study, demonstrating that conversion of patients from inducers to TPM results in sharp declines in CRP similar to those seen when patients are switched to LTG or LEV.…”

Plaques on the Wall: Inducing Anticonvulsant Use and Atherogenesis

“…A previous study by these authors, along with two other studies from different groups, demonstrated that CIMT is elevated in drug-treated epilepsy patients, though there was no separation of individual drugs' effects (8)(9)(10). This time, the authors assessed CIMT in epilepsy patients treated with one of four drugs-carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), or lamotrigine (LTG)-in monotherapy.…”