Why are epilepsy mortality rates rising in the United States? A population-based multiple cause-of-death study

DeGiorgio, Christopher M.; Curtis, Ashley; Carapetian, Armen; Hovsepian, Dominic A.; Krishnadasan, Anusha; Markovic, Daniela

doi:10.1136/bmjopen-2019-035767

Cited by 39 publications

(37 citation statements)

References 25 publications

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“…3 Mortality rates of PWE are higher than for the general population. [4][5][6][7][8][9] A longitudinal cohort study from Sweden found that an epilepsy diagnosis was associated with a 14-fold increased risk of all-cause death. 5 Some studies suggest that this has not changed over time.…”

Section: Introductionmentioning

confidence: 99%

Epilepsy and mortality: a retrospective cohort analysis with a nested case–control study identifying causes and risk factors from primary care and linkage-derived data

et al. 2021

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ObjectivesPeople with epilepsy (PWE) have a higher mortality rate than the general population. Epilepsy-related deaths have increased despite all-cause mortality decreasing in the general population pre-COVID-19. We hypothesised that clinical and lifestyle factors may identify people more at risk.DesignWe used a retrospective cohort study to explore cause of death and a nested case–control study to identify risk factors.SettingWe explored factors associated with mortality using primary care population data from 1 April 2004 to 31 March 2014. Data were obtained from the Clinical Practice Research Datalink which compiles anonymised patient data from primary care in the UK. Cause of death data was supplemented from the Office of National Statistics when available.ParticipantsThe analysis included 70 431 PWE, with 11 241 registered deaths.ResultsThe number of deaths within the database increased by 69% between the first and last year of the study. Epilepsy was considered as a contributing cause in approximately 45% of deaths of PWE under 35. Factors associated with increased risk of death included attendance at emergency departments and/or emergency admissions (OR 3.48, 95% CI 3.19 to 3.80), antiepileptic drug (AED) polytherapy (2 AEDs: OR 1.60, 95% CI 1.51 to 1.71; 3 AEDs: OR 2.06, 95% CI 1.86 to 2.29; 4+AEDs: OR 2.62, 95% CI 2.23 to 3.08), status epilepticus (OR 2.78, 95% CI 1.64 to 4.71), depression (OR 1.67, 95% CI 1.57 to 1.76) and injuries (OR 1.54, 95% CI 1.43 to 1.67). No seizures in the prior year (OR 0.52, 95% CI 0.41 to 0.65).ConclusionOur results add to existing evidence that deaths in epilepsy are increasing. Future studies could focus on identifying PWE at high risk and addressing them with clinical interventions or better self-management. Identifying specific risk factors for younger people should be a priority as epilepsy may be a factor in close to half of deaths of PWE under 35 years of age.

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Section: Introductionmentioning

confidence: 99%

Epilepsy and mortality: a retrospective cohort analysis with a nested case–control study identifying causes and risk factors from primary care and linkage-derived data

et al. 2021

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“…Epilepsy is a burdensome neurological disease known to increase mortality by up to 10 times among afflicted persons [ 1 , 2 ]. As secondary causes of epilepsy and co-existent neurological diseases become more prevalent, ageing populations are expected to face a rise in epilepsy-related mortality [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Mortality among People with Epilepsy: A Retrospective Nationwide Analysis from 2016 to 2019

Puteikis

Mameniškienė

2021

IJERPH

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We estimated age-adjusted mortality and investigated the dominant causes of death as well as comorbidities among people with epilepsy (PWE) in Lithuania, a country with frequent deaths from external causes. From 2016 to 2019, the age-adjusted rate of death among PWE in Lithuania was compared with mortality data in the general population. Each year of analysis, individuals who were diagnosed with epilepsy comprised a retrospective cohort. The standardized mortality ratio (SMR) of PWE varied from 2.93 (95% CI 2.78 to 3.07) to 3.18 (95% CI 3.02 to 3.34). PWE died at least one decade earlier than expected in the general population. The dominant causes of death were cardiovascular diseases (their proportion ranged from 44.8% to 49.3%), cancer (16.7% to 21.3%) and external causes of death (8.5% to 10.9%). The proportion of the latter decreased over time (r = −0.99, p = 0.01), whereas the SMR for external causes of death remained relatively constant. Epilepsy was the underlying cause of death in 163 cases (2.6%), and noted as a condition contributing to death in 1010 cases (15.9%). Cerebrovascular and cardiological conditions and dementia were the most frequent comorbidities among PWE before their death. Epilepsy-unrelated causes of death are relevant contributors to mortality among PWE. There is a need for PWE-oriented societal interventions to reduce the frequency of external deaths beyond the trend in the general population.

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“…This database captures all death certificates where epilepsy, ICD‐10 G40.0 through G40.9 are listed as the underlying cause or one of up to twenty contributing causes of death. The CDC multiple cause‐of‐death database allows identification of significantly greater epilepsy deaths then the single underlying cause‐of‐death database 7 …”

Section: Discussionmentioning

confidence: 99%

“…However, despite the introduction of new anti‐seizure medications (ASMs) and devices, seizure‐free rates in 2018 remain unchanged from the year 2000 5,6 . In fact, epilepsy mortality rates are rising, due to higher prevalence and increases in the global burden of neurological disease 7 . Over the same period, primary prevention strategies for cardiovascular disease have dramatically reduced mortality in the general population 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Changes in epilepsy causes of death: A US population study

et al. 2021

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Objectives Since 2000, medical treatment for epilepsy and cardiovascular risk‐reduction strategies have advanced significantly in the United States (US). However, seizure‐free rates remain unchanged, and people with epilepsy are at higher risk than the general population for heart disease and stroke. The purpose of this study is to determine how cardiovascular, epilepsy‐related, and other causes of death are changing in epilepsy in comparison with the US population. Materials & Methods Changes in the 15 underlying causes of death in epilepsy (ICD‐10 G40‐G40.9) and the US population were analyzed and compared from 2000 to 2018. The CDC multiple cause‐of‐death database was utilized as the primary data source. Changes in the relative proportions for each cause‐of‐death over were evaluated using logistic regression. Results The proportions of deaths in epilepsy due to heart disease declined 34.4% (p < .001), a rate similar to the general population (39.9%). Epilepsy‐related deaths declined 25% as a percentage of all epilepsy deaths (p < .001). The proportions of deaths due to stroke and neoplasms increased significantly in epilepsy versus the US population (p < .001 linear trend). Conclusions The reduction in ischemic heart disease in epilepsy is a novel and highly significant finding, which reflects widespread implementation of cardiovascular risk‐factor reduction and treatment in the United States. Reductions in epilepsy‐related deaths are an exciting development which requires further investigation into causality. The increase in deaths due to neoplasms and stroke relative to the US population is concerning, warranting vigilance and increased efforts at recognition, prevention, and treatment.

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Why are epilepsy mortality rates rising in the United States? A population-based multiple cause-of-death study

Cited by 39 publications

References 25 publications

Epilepsy and mortality: a retrospective cohort analysis with a nested case–control study identifying causes and risk factors from primary care and linkage-derived data

Epilepsy and mortality: a retrospective cohort analysis with a nested case–control study identifying causes and risk factors from primary care and linkage-derived data

Mortality among People with Epilepsy: A Retrospective Nationwide Analysis from 2016 to 2019

Changes in epilepsy causes of death: A US population study

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