Summary 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 enzyme‐inducers (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 enzyme‐inhibiting 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 long‐term AED therapy, particularly in aged and high‐risk individuals.

Background and Purpose— Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for angiogenesis in situ. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke (IS). Methods— The level of circulating EPCs (staining markers: CD31/CD34 [E 1 ], CD62E/CD34 [E 2 ], and KDR/CD34 [E 3 ]) were examined using flow cytometry at 48 hours after acute IS in 138 consecutive patients. The EPC level was also evaluated once in 20 healthy volunteers and in 40 at-risk control subjects. Results— Level of circulating EPCs (E 1–3 ) was significantly higher in patients with IS than in at-risk control subjects ( P <0.05). Additionally, EPC (E 1–3 ) level was significantly lower in patients with severe neurological impairment (defined as a score ≥12 on the National Institutes of Health Stroke Scale) than in patients with less severe impairment (National Institutes of Health Stroke Scale < score 12) at 48 hours after IS ( P <0.0001). Moreover, the EPC (E 3 ) level was strongly correlated with improved National Institutes of Health Stroke Scale ≥4 on day 21 after IS ( P =0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (National Institutes of Health Stroke Scale ≥12) at 48 hours (E 1–3 ) and combined major adverse clinical outcomes (defined as recurrent IS, any cause of death, or National Institutes of Health Stroke Scale of ≥12) on day 90 (E 1 ) after IS ( P <0.001). Conclusions— Level of circulating EPCs is independently predictive of prognosis after IS.

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.