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Year : 2009  |  Volume : 57  |  Issue : 4  |  Page : 504

Long-term effects of antiepileptic therapy on cardiovascular risk factors in children

Department of Pediatrics, GATA Haydarpasa Teaching Hospital, Istanbul, Turkey

Date of Acceptance09-Jan-2009
Date of Web Publication10-Sep-2009

Correspondence Address:
Cihan Meral
Department of Pediatrics, GATA Haydarpasa Teaching Hospital, Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.55585

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How to cite this article:
Aydemir G, Meral C, Suleymanoglu S, Karademir F. Long-term effects of antiepileptic therapy on cardiovascular risk factors in children. Neurol India 2009;57:504

How to cite this URL:
Aydemir G, Meral C, Suleymanoglu S, Karademir F. Long-term effects of antiepileptic therapy on cardiovascular risk factors in children. Neurol India [serial online] 2009 [cited 2021 Jun 20];57:504. Available from:


Risk factors for atherosclerosis appear even in children, and early atherosclerotic changes begin to appear in childhood. One of the many new risk factors that is attracting ever greater scientific interest, and whose role in the development of atherosclerotic changes is indisputable, is homocysteine. Carbamazepine (CBZ) and valproic acid (VPA) lower serum folate and vitamin-B12 levels and increase homocysteine levels.The purpose of our study was to evaluate total plasma homocysteine concentrations and other cardiovascular risk factors in children on long-term (over five years) antiepileptic therapy, and to attempt to identify possible relationship between homocysteine and the degree of vitamin deficiencies.

The study subjects included 60 children (32 female, 28 male, mean age: 8.5 ± 3 years, age range: 2,5-15 years) using CBZ and VPA and 30 age-, sex- and body mass index-matched healthy children as control subjects. Fasting samples were collected for plasma total homocysteine, serum vitamin B, serum folate, lipoprotein (a), ApoB and urine methylmalonic acid. Duration of CBZ and VPA therapy was 6.83 ± 1 .10 and 6.44 ± 1.07 years, respectively. Plasma total homocysteine (13.1 ± 5.4 vs. 8.6 ± 3 .5 mmol/l, P, 0.001), urine methylmalonic acid (42.1 ± 51 vs. 8.3 ± 4 .6mmol/mol creatinine, P< 0.001), lipoprotein (a) (25.4 ±29 .1 vs. 9.0 ± 3 .8mg/dl, P< 0.001) were significantly higher in children receiving CBZ and VPA when compared to control subjects. The study group had significantly lower serum vitamin B 12 >(356 ± 115.8 vs. 513±165.6pg/ml, P< 0.001), serum folate (6.8 ± 2.7 vs. 12.59 ± 4.6ng/mL P< 0.001), and ApoB (89.± 6 15.9 vs. 68.6 ± 13.9mg/dl, P, 0.001) than control group. Plasma total homocysteine, serum folate and lipoprotein (a) levels were slightly higher in CBZ-receiving group when compared to VPA-receiving group, but with no statistical significance. However, urine methylmalonic acid levels were significantly higher in the CBZ group than in the VPA group (62.1 ± 65 .4 vs. 22.2 ± 13 .8mmol/mol creatinine, P : 0.002).

In the present study, we demonstrated that homocysteine levels in children using CBZ and VPA were slightly higher than healthy subjects and also homocysteine levels was significantly associated with urine methylmalonic acid. The measurement of serum or urine concentrations of methylmalonic acid and plasma homocysteine metabolites related to vitamin B 12 deficiency has been used to establish vitamin B 12 deficiency at the biochemical level. In conclusion, we suggest that urine methylmalonic acid may be a reliable indicator for vitamin deficiencies in children under prolonged antiepileptic therapy.[4]

  References Top

1.Berenson GS, Srinivasan SR, Bao W, Newman WP 3 rd , Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med 1998;338:1650-6.  Back to cited text no. 1    
2.Berenson GS, Wattigney WA, Tracy RE, Newman WP 3 rd , Srinivasan SR, Webber LS, . Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (the Bogalusa Heart Study). Am J Cardiol 1992;70:851-8.  Back to cited text no. 2    
3.Verrotti A, Pasceralla R, Trotta D, Giuva T, Morgese G, Chiarelli F. Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res 2000;41:253-7.  Back to cited text no. 3    
4.Allen RH, Stabler SP, Savage DG, Lindenbaum J. Diagnosis of cobalamin deficiency, I: Usefulness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol 1990;34:90-8.  Back to cited text no. 4    

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1 Antiepileptic drugs
Zaccara, G. and Tramacere, L.
Side Effects of Drugs Annual. 2011; 33(1): 125-204


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