Valproate attenuates the risk of myocardial infarction in patients with epilepsy: A nationwide cohort study

Pharmacoepidemiology and Drug Safety

Volumn 20, Issue 2, 2011, Pages 146-153

  Olesen, Jonas Bjerring ^a   Hansen, Peter Riis ^a   Abildstrøm, Steen Zabell ^b,c   Andersson, Charlotte ^a   Weeke, Peter ^a   Schmiegelow, Michelle ^a   Erdal, Jesper ^a   Torp Pedersen, Christian ^a   Gislason, Gunnar Hilmar ^a  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c BISPEBJERG HOSPITAL   (Denmark)

Author keywords

Epidemiology; Epilepsy; Myocardial infarction; Pharmacology; Valproate

Indexed keywords

ANTIDEPRESSANT AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOOP DIURETIC AGENT; NEUROLEPTIC AGENT; SPIRONOLACTONE; VALPROIC ACID;

ADULT; ARTICLE; ATTENUATION; CARDIOVASCULAR RISK; CAUSE OF DEATH; COHORT ANALYSIS; CONFIDENCE INTERVAL; CONTROLLED STUDY; DISEASE ASSOCIATION; EPILEPSY; FEMALE; HAZARD RATIO; HEART INFARCTION; HUMAN; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROPORTIONAL HAZARDS MODEL; TREATMENT DURATION;

ADULT; AGED; ANTICONVULSANTS; CASE-CONTROL STUDIES; CAUSE OF DEATH; CHI-SQUARE DISTRIBUTION; COHORT STUDIES; DENMARK; EPILEPSY; FEMALE; HEALTH CARE SURVEYS; HUMANS; MALE; MIDDLE AGED; MYOCARDIAL INFARCTION; PROPORTIONAL HAZARDS MODELS; REGISTRIES; RISK ASSESSMENT; RISK FACTORS; TIME FACTORS; TREATMENT OUTCOME; VALPROIC ACID;

EID: 78751687375     PISSN: 10538569     EISSN: 10991557     Source Type: Journal    
DOI: 10.1002/pds.2073     Document Type: Article

References (39)

1. Gunes A, Bilir E, Zengil H, Babaoglu MO, Bozkurt A, Yasar U. Inhibitory effect of valproic acid on cytochrome p450 2c9 activity in epilepsy patients. Basic Clin Pharmacol Toxicol 2007; 100: 383-386.
2. Bowes AJ, Khan MI, Shi Y, Robertson L, Werstuck GH. Valproate attenuates accelerated atherosclerosis in hyperglycemic apoe-deficient mice: evidence in support of a role for endoplasmic reticulum stress and glycogen synthase kinase-3 in lesion development and hepatic steatosis. Am J Pathol 2009; 174: 330-342.
3. Khan MI, Pichna BA, Shi Y, Bowes AJ, Werstuck GH. Evidence supporting a role for endoplasmic reticulum stress in the development of atherosclerosis in a hyperglycaemic mouse model. Antioxid Redox Signal 2009; 11: 2289-2298.
4. Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects cells from er stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 2005; 118: 89-99.
5. Lee TM, Lin MS, Chang NC. Inhibition of histone deacetylase on ventricular remodeling in infarcted rats. Am J Physiol Heart Circ Physiol 2007; 293: H968-H977.
6. Pylvanen V, Knip M, Pakarinen AJ, et al. Fasting serum insulin and lipid levels in men with epilepsy. Neurology 2003; 60: 571-574.
7. Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin b12, folic acid and vitamin b6. Seizure 2006; 15: 79-85.
8. Verrotti A, la Torre R, Trotta D, Mohn A, Chiarelli F. Valproate-induced insulin resistance and obesity in children. Horm Res 2009; 71: 125-131.
9. Verrotti A, Scardapane A, Franzoni E, Manco R, Chiarelli F. Increased oxidative stress in epileptic children treated with valproic acid. Epilepsy Res 2008; 78: 171-177.
10. Chengappa KN, Chalasani L, Brar JS, Parepally H, Houck P, Levine J. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review. Clin Ther 2002; 24: 1576-1584.
11. Martin C, Han H, Anton S, Greenway F, Smith S. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol 2009; 23: 814-825.
12. Janszky I, Hallqvist J, Tomson T, Ahlbom A, Mukamal KJ, Ahnve S. Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy-the stockholm heart epidemiology program. Brain 2009; 132: 2798-2804.
13. Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia 2004; 45: 1613-1622.
14. Nilsson L, Tomson T, Farahmand BY, Diwan V, Persson PG. Cause-specific mortality in epilepsy: a cohort study of more than 9, 000 patients once hospitalized for epilepsy. Epilepsia 1997; 38: 1062-1068.
15. Gaist D, Sorensen HT, Hallas J. The danish prescription registries. Dan Med Bull 1997; 44: 445-448.
16. Olesen JB, Hansen PR, Erdal J, et al. Antiepileptic drugs and risk of suicide: a nationwide study. Pharmacoepidemiol Drug Saf 2010; 19: 518-524.
17. Fosbol EL, Gislason GH, Jacobsen S, et al. The pattern of use of non-steroidal anti-inflammatory drugs (nsaids) from 1997 to 2005: a nationwide study on 4.6 million people. Pharmacoepidemiol Drug Saf 2008; 17: 822-833.
18. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with icd-9-cm administrative databases. J Clin Epidemiol 1992; 45: 613-619.
19. Nuttall M, van der Meulen J, Emberton M. Charlson scores based on icd-10 administrative data were valid in assessing comorbidity in patients undergoing urological cancer surgery. J Clin Epidemiol 2006; 59: 265-273.
20. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-383.
21. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. Available at: [Accessed on 24 February 2010].
22. Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of antiepileptic drugs on lipids, homocysteine, and c-reactive protein. Ann Neurol 2009; 65: 448-456.
23. de Chadarevian JP, Legido A, Miles DK, Katsetos CD. Epilepsy atherosclerosis, myocardial infarction, and carbamazepine. J Child Neurol 2003; 18: 150-151.
24. Hamed SA, Hamed EA, Hamdy R, Nabeshima T. Vascular risk factors and oxidative stress as independent predictors of asymptomatic atherosclerosis in adult patients with epilepsy. Epilepsy Res 2007; 74: 183-192.
25. Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol 2003; 2: 347-356.
26. Gerstner T, Teich M, Bell N, et al. Valproate-associated coagulopathies are frequent and variable in children. Epilepsia 2006; 47: 1136-1143.
27. Gerstner T, Woelfing C, Witsch M, Longin E, Bell N, Konig S. Capillary microscopy and hemorheology in children during antiepileptic monotherapy with carbamazepine and valproate. Seizure 2006; 15: 606-609.
28. Koenig S, Gerstner T, Keller A, Teich M, Longin E, Dempfle CE. High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study. Blood Coagul Fibrinolysis 2008; 19: 375-382.
29. Zeller JA, Schlesinger S, Runge U, Kessler C. Influence of valproate monotherapy on platelet activation and hematologic values. Epilepsia 1999; 40: 186-189.
30. Marciniak SJ, Ron D. Endoplasmic reticulum stress signaling in disease. Physiol Rev 2006; 86: 1133-1149.
31. Werstuck GH, Khan MI, Femia G, et al. Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model. Diabetes 2006; 55: 93-101.
32. Best PJ, Hasdai D, Sangiorgi G, et al. Apoptosis basic concepts and implications in coronary artery disease. Arterioscler Thromb Vasc Biol 1999; 19: 14-22.
33. Valen G, Yan ZQ, Hansson GK. Nuclear factor kappa-b and the heart. J Am Coll Cardiol 2001; 38: 307-314.
34. Song L, De Sarno P, Jope RS. Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress-induced caspase-3 activation. J Biol Chem 2002; 277: 44701-44708.
35. Juhaszova M, Zorov DB, Kim SH, et al. Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 2004; 113: 1535-1549.
36. Murphy E. Inhibit gsk-3beta or there's heartbreak dead ahead. J Clin Invest 2004; 113: 1526-1528.
37. Tong H, Imahashi K, Steenbergen C, Murphy E. Phosphorylation of glycogen synthase kinase-3beta during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective. Circ Res 2002; 90: 377-379.
38. Christensen J, Vestergaard M, Olsen J, Sidenius P. Validation of epilepsy diagnoses in the danish national hospital register. Epilepsy Res 2007; 75: 162-170.
39. Madsen M, Davidsen M, Rasmussen S, Abildstrom SZ, Osler M. The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the danish monica registry. J Clin Epidemiol 2003; 56: 124-130.