{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T18:03:58Z","timestamp":1784397838539,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Using a Dutch insurance claims registry, we examine whether people with epilepsy have an increased risk of major ischemic cardiovascular events or death compared to people without epilepsy. We also assess whether this risk differs between users of enzyme\u2010modulating and non\u2010enzyme\u2010modulating antiseizure medications (ASMs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This nationwide study included adults \u226550\u2009years old in the VEKTIS registry. Incident seizure cases were matched 2:1 to controls by age, sex, and region. ASM prescriptions (\u22656\u2009months) were classified as enzyme\u2010modulating or non\u2010enzyme\u2010modulating. The primary outcome was a composite event over 5\u2010year follow\u2010up. Cox models adjusted for age, sex, and baseline cardiovascular medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We matched 8728 cases to 17\u2009445 controls (56% male, median age\u2009=\u200967\u2009years, range\u2009=\u200950\u2013102). During follow\u2010up, 6895 events occurred. Seizure disorder was associated with a higher cardiovascular risk than controls (hazard ratio [HR]\u2009=\u20092.30, 95% confidence interval [CI] =\u20092.19\u20132.41,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001), particularly early after diagnosis. Older age and cardiovascular medication use increased risk, whereas female sex was protective. Among 1758 participants with seizures treated with ASM, 656 events occurred. The enzyme\u2010modulating ASM group showed a nonsignificant trend toward higher risk than the non\u2010enzyme\u2010modulating ASM group (HR\u2009=\u20091.14, 95% CI = .97\u20131.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.12). Time\u2010varying models suggested a lower risk with current enzyme\u2010modulating ASM exposure compared with non\u2010enzyme\u2010modulating ASMs (HR\u2009=\u2009.80, 95% CI = .70\u2013.92,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.001). There was an increased risk with cumulative exposure (HR\u2009=\u20091.41 per year of past enzyme\u2010modulating ASM exposure, 95% CI\u2009=\u20091.30\u20131.54,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>People with seizures face higher cardiovascular risk, especially shortly after diagnosis. Although short\u2010term analyses showed no clear differences between ASM categories, longer term and cumulative exposure to enzyme\u2010modulating ASMs was associated with modestly increased risk. Findings are generalizable to routine care, although further work is needed to clarify time\u2010 and drug\u2010specific cardiovascular effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70389","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:29:40Z","timestamp":1784395780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular events and mortality in adults with late onset seizures: Focus on enzyme\u2010modulating antiseizure medications"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8758-9828","authenticated-orcid":false,"given":"Paola","family":"Vassallo","sequence":"first","affiliation":[{"name":"UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  UK"},{"name":"Stichting Epilepsie Instellingen Nederland  Heemstede the Netherlands"},{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-6125","authenticated-orcid":false,"given":"Nathan A.","family":"Shlobin","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland  Heemstede the Netherlands"},{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Neurosurgery, Neurological Institute of New York New York Presbyterian Hospital\u2013Columbia University Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2807-7347","authenticated-orcid":false,"given":"Mark R.","family":"Keezer","sequence":"additional","affiliation":[{"name":"Neurology Division Centre Hospitalier de L'universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Centre de Recherche Centre Hospitalier de L'universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"School of Public Health Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1435-8970","authenticated-orcid":false,"given":"Roland D.","family":"Thijs","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  UK"},{"name":"Stichting Epilepsie Instellingen Nederland  Heemstede the Netherlands"},{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-9661","authenticated-orcid":false,"given":"Ley","family":"Sander","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  UK"},{"name":"Stichting Epilepsie Instellingen Nederland  Heemstede the Netherlands"},{"name":"Department of Neurology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2012.03671.x"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16966"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2022.2023128"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2016.10.001"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102015\u2010008365"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.03.008"},{"key":"e_1_2_13_8_1","unstructured":"ATCDDD \u2013 Definition and general 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