{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:37:33Z","timestamp":1791067053499,"version":"4.1.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:sec id=\"ab-noi240061-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>How epilepsy may promote cardiovascular disease remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate the odds of new-onset cardiovascular events (CVEs) over 6 years in older people with vs without epilepsy, exploring how enzyme-inducing antiseizure medications (EIASMs) and traditional cardiovascular risk factors mediate these odds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a prospective cohort study using the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA), with 6 years of follow-up (2015-2021, analysis performed in December 2023). The CLSA is an ongoing, national study of 51\u202f338 adults aged 45 to 85 years at baseline who are recruited in Canada. The comprehensive cohort includes 30\u202f097 individuals living near 1 of 11 data collection centers. Participation in the CLSA was voluntary; participation rate was 45%. Among those in the comprehensive cohort, individuals reporting no previous history of CVEs (ie, stroke, transient ischemic attack [TIA], or myocardial infarction [MI]) at baseline were excluded. No other exclusion criteria were applied. A total of 86% of participants completed follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>Lifetime history of epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was new-onset CVEs over 6 years. Secondary outcomes were new-onset strokes, TIAs, and MIs. Logistic models were fitted for these outcomes as a function of epilepsy, age, sex, household income, and education level. Mediation analyses were conducted for strong EIASM use, weak EIASM use, Framingham score, Physical Activity Scale for the Elderly (PASE) score, and waist to hip ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 30\u202f097 individuals in the comprehensive cohort, a total of 27\u202f230 individuals (mean [SD] age, 62.3 [10.1] years; 14\u202f268 female [52.4%]) were included, 431 with a lifetime history of epilepsy. New-onset CVEs were more likely in epilepsy, with an adjusted odds ratio of 2.20 (95% CI, 1.48-3.27). The proportion of the effect of epilepsy on new-onset CVEs was mediated as follows by each of the following variables: strong EIASM use, 24.6% (95% CI, 6.5%-54.6%), weak EIASM use, 4.0% (95% CI, 0.8%-11.0%), Framingham score, 1.4% (95% CI, \u22121.6% to 4.5%), PASE score, 3.3% (95% CI, 1.4%-6.8%), and waist to hip ratio, 1.6% (95% CI, 0.4%-3.7%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi240061-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results of this cohort study reveal that epilepsy was associated with new-onset CVEs. Nearly one-third of this association can be explained by EIASMs. These findings should be considered when choosing an antiseizure medication for a person at risk for cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.3210","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T11:32:27Z","timestamp":1727695947000},"page":"1178","source":"Crossref","is-referenced-by-count":23,"title":["Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy in the Canadian Longitudinal Study on Aging"],"prefix":"10.1001","volume":"81","author":[{"given":"Jimmy","family":"Li","sequence":"first","affiliation":[{"name":"Neurology Division, Centre Hospitalier de l\u2019Universit\u00e9 de Sherbrooke, Sherbrooke, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"Shlobin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland D.","family":"Thijs","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands"},{"name":"Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands"},{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Sylvestre","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"School of Public Health, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin B.","family":"Josephson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada"},{"name":"O\u2019Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada"},{"name":"Centre for Health Informatics, University of Calgary, Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Deacon","sequence":"additional","affiliation":[{"name":"Neurology Division, Centre Hospitalier de l\u2019Universit\u00e9 de Sherbrooke, Sherbrooke, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Keezer","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom"},{"name":"School of Public Health, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"noi240061r1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1212\/WNL.0000000000003509","article-title":"Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies.","volume":"88","author":"Fiest","year":"2017","journal-title":"Neurology"},{"issue":"4","key":"noi240061r2","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.rcl.2008.07.005","article-title":"Epidemiology of aging.","volume":"46","author":"Ferrucci","year":"2008","journal-title":"Radiol Clin North Am"},{"issue":"10225","key":"noi240061r3","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S0140-6736(19)33064-8","article-title":"Epilepsy in older people.","volume":"395","author":"Sen","year":"2020","journal-title":"Lancet"},{"issue":"1","key":"noi240061r4","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S1474-4422(15)00225-2","article-title":"Comorbidities of epilepsy: current concepts and future perspectives.","volume":"15","author":"Keezer","year":"2016","journal-title":"Lancet Neurol"},{"issue":"11","key":"noi240061r5","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/S1474-4422(09)70240-6","article-title":"Epilepsy in later life.","volume":"8","author":"Brodie","year":"2009","journal-title":"Lancet Neurol"},{"issue":"pt B","key":"noi240061r6","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.05.005","article-title":"Increased risk of stroke and myocardial infarction in patients with epilepsy: a systematic review of population-based cohort studies.","volume":"104","author":"Brigo","year":"2020","journal-title":"Epilepsy Behav"},{"issue":"11","key":"noi240061r7","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1001\/jamaneurol.2021.3424","article-title":"Association of enzyme-inducing antiseizure drug use with long-term cardiovascular disease.","volume":"78","author":"Josephson","year":"2021","journal-title":"JAMA Neurol"},{"key":"noi240061r8","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.106946","article-title":"The epileptic heart: concept and clinical evidence.","volume":"105","author":"Verrier","year":"2020","journal-title":"Epilepsy Behav"},{"issue":"9596","key":"noi240061r9","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"370","author":"von Elm","year":"2007","journal-title":"Lancet"},{"issue":"6","key":"noi240061r10","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1093\/ije\/dyz173","article-title":"Cohort Profile: The Canadian Longitudinal Study on Aging (CLSA).","volume":"48","author":"Raina","year":"2019","journal-title":"Int J Epidemiol"},{"issue":"11","key":"noi240061r11","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1111\/epi.12805","article-title":"The diagnostic test accuracy of a screening questionnaire and algorithm in the identification of adults with epilepsy.","volume":"55","author":"Keezer","year":"2014","journal-title":"Epilepsia"},{"issue":"2","key":"noi240061r12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/0895-4356(93)90053-4","article-title":"The Physical Activity Scale for the Elderly (PASE): development and evaluation.","volume":"46","author":"Washburn","year":"1993","journal-title":"J Clin Epidemiol"},{"issue":"6","key":"noi240061r13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/S1474-4422(03)00409-5","article-title":"Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs.","volume":"2","author":"Patsalos","year":"2003","journal-title":"Lancet Neurol"},{"issue":"6","key":"noi240061r14","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1161\/CIRCULATIONAHA.107.699579","article-title":"General cardiovascular risk profile for use in primary care.","volume":"117","author":"D\u2019Agostino","year":"2008","journal-title":"Circulation"},{"key":"noi240061r16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v045.i03","article-title":"Mice: multivariate imputation by chained equations in R.","volume":"45","author":"Van Buuren","year":"2011","journal-title":"J Stat Softw"},{"key":"noi240061r18","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jclinepi.2021.08.001","article-title":"Tutorial on directed acyclic graphs.","volume":"142","author":"Digitale","year":"2022","journal-title":"J Clin Epidemiol"},{"issue":"3","key":"noi240061r19","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1017\/S0714980809990055","article-title":"The Canadian Longitudinal Study on Aging (CLSA).","volume":"28","author":"Raina","year":"2009","journal-title":"Can J Aging"},{"issue":"4","key":"noi240061r20","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1037\/a0020761","article-title":"A general approach to causal mediation analysis.","volume":"15","author":"Imai","year":"2010","journal-title":"Psychol Methods"},{"issue":"5","key":"noi240061r21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v059.i05","article-title":"Mediation: R package for causal mediation analysis.","volume":"59","author":"Tingley","year":"2014","journal-title":"J Stat Softw"},{"issue":"15","key":"noi240061r22","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1002\/sim.7643","article-title":"On the use of the not-at-random fully conditional specification (NARFCS) procedure in practice.","volume":"37","author":"Tompsett","year":"2018","journal-title":"Stat Med"},{"issue":"5","key":"noi240061r23","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1097\/EDE.0000000000000864","article-title":"Web site and R package for computing E-values.","volume":"29","author":"Mathur","year":"2018","journal-title":"Epidemiology"},{"issue":"4","key":"noi240061r24","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in observational research: introducing the E-value.","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"issue":"5","key":"noi240061r25","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.seizure.2014.02.007","article-title":"Patients with epilepsy are at an increased risk of subsequent stroke: a population-based cohort study.","volume":"23","author":"Chang","year":"2014","journal-title":"Seizure"},{"issue":"9416","key":"noi240061r26","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/S0140-6736(04)15946-1","article-title":"Late-onset seizures as a predictor of subsequent stroke.","volume":"363","author":"Cleary","year":"2004","journal-title":"Lancet"},{"key":"noi240061r27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.atherosclerosis.2018.11.009","article-title":"Stroke risk and outcomes in epilepsy patients: 2 retrospective cohort studies based on national health insurance in Taiwan.","volume":"280","author":"Hsu","year":"2019","journal-title":"Atherosclerosis"},{"issue":"9","key":"noi240061r28","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1002\/pds.2186","article-title":"Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study.","volume":"20","author":"Olesen","year":"2011","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"noi240061r29","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.yebeh.2014.11.028","article-title":"Stroke after adult-onset epilepsy: a population-based retrospective cohort study.","volume":"43","author":"Wannamaker","year":"2015","journal-title":"Epilepsy Behav"},{"key":"noi240061r30","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.yebeh.2018.09.009","article-title":"Myocardial infarction after epilepsy onset: a population-based retrospective cohort study.","volume":"88","author":"Wilson","year":"2018","journal-title":"Epilepsy Behav"},{"issue":"1-2","key":"noi240061r31","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3109\/07853890.2016.1140225","article-title":"Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: a prospective case-control study.","volume":"48","author":"Hookana","year":"2016","journal-title":"Ann Med"},{"issue":"4","key":"noi240061r32","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s11940-010-0080-y","article-title":"Antiepileptic drugs and markers of vascular risk.","volume":"12","author":"Lopinto-Khoury","year":"2010","journal-title":"Curr Treat Options Neurol"},{"key":"noi240061r33","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.yebeh.2014.03.008","article-title":"Use of antiepileptic drugs and lipid-lowering agents in the US.","volume":"34","author":"Mintzer","year":"2014","journal-title":"Epilepsy Behav"},{"issue":"1","key":"noi240061r34","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1528-1167.2012.03671.x","article-title":"Enzyme induction with antiepileptic drugs: cause for concern?","volume":"54","author":"Brodie","year":"2013","journal-title":"Epilepsia"},{"key":"noi240061r35","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.yebeh.2016.02.023","article-title":"Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein.","volume":"58","author":"Mintzer","year":"2016","journal-title":"Epilepsy Behav"},{"issue":"10","key":"noi240061r36","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1111\/epi.14554","article-title":"Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly.","volume":"59","author":"Mintzer","year":"2018","journal-title":"Epilepsia"},{"key":"noi240061r37","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2022.108610","article-title":"Complications associated with the use of enzyme-inducing and non\u2013enzyme-inducing antiseizure medications in the Japanese population: a retrospective cohort study.","volume":"129","author":"Gao","year":"2022","journal-title":"Epilepsy Behav"},{"issue":"7","key":"noi240061r38","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1111\/epi.16930","article-title":"Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events.","volume":"62","author":"Lee-Lane","year":"2021","journal-title":"Epilepsia"},{"key":"noi240061r39","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.yebeh.2014.06.013","article-title":"Social determinants of health in epilepsy.","volume":"41","author":"Szaflarski","year":"2014","journal-title":"Epilepsy Behav"},{"issue":"5","key":"noi240061r40","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1161\/CIRCRESAHA.121.319811","article-title":"Social determinants of cardiovascular disease.","volume":"130","author":"Powell-Wiley","year":"2022","journal-title":"Circ Res"},{"issue":"13","key":"noi240061r41","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.029765","article-title":"The role of social determinants of health in cardiovascular diseases: an umbrella review.","volume":"12","author":"Teshale","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"4","key":"noi240061r42","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3988\/jcn.2017.13.4.371","article-title":"Effects of antiepileptic drugs on the carotid artery intima-media thickness in epileptic patients.","volume":"13","author":"Lai","year":"2017","journal-title":"J Clin Neurol"},{"issue":"8","key":"noi240061r43","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1111\/epi.16966","article-title":"Epileptic heart: a clinical syndromic approach.","volume":"62","author":"Verrier","year":"2021","journal-title":"Epilepsia"},{"issue":"9","key":"noi240061r44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137538","article-title":"Accuracy of patient self-report of stroke: a systematic review from the UK Biobank stroke outcomes group.","volume":"10","author":"Woodfield","year":"2015","journal-title":"PLoS One"},{"key":"noi240061r15","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2013"},{"key":"noi240061r17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1201\/9780429492259","volume-title":"Flexible Imputation of Missing Data","author":"Van Buuren","year":"2018","edition":"2nd ed"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2824203\/jamaneurology_li_2024_oi_240061_1736448746.1776.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T11:02:22Z","timestamp":1736766142000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2824203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,1]]},"references-count":44,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2024.3210","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11,1]]}}}