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

• Published in: Epilepsia (Copenhagen) 2009-06, Vol.50 (6), p.1579-1586
• Main Authors: Tan, Teng‐Yeow, Lu, Cheng‐Hsien, Chuang, Hung‐Yi, Lin, Tsu‐Kung, Liou, Chia‐Wei, Chang, Wen‐Neng, Chuang, Yao‐Chung
• Format: Article
• Language: English
• Subjects: Adult; Anticonvulsants - adverse effects; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic drug therapy; Atherosclerosis; Biological and medical sciences; Carotid Artery Diseases - chemically induced; Case-Control Studies; Epilepsy - classification; Epilepsy - drug therapy; Epilepsy - etiology; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Intima media thickness; Intracranial Arteriosclerosis - chemically induced; Longitudinal Studies; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Oxidative stress; Pharmacology. Drug treatments; Regression Analysis; Retrospective Studies; Risk Factors
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2009.02024.x

Summary Purpose:  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 B‐mode 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.