Is Cardiovascular Mortality Among People with Epilepsy increasing? A retrospective US population study.

INTRODUCTION: People with epilepsy are at higher risk for hypertension, diabetes, hyperlipidaemia and obesity than the US general population. It is unknown whether these risk factors translate to increased cardiovascular mortality compared with the US general population. OBJECTIVE: To examine changes in the proportions of deaths due to cardiovascular causes among people with epilepsy in the USA. HYPOTHESIS: Cardiovascular mortality among people with epilepsy is rising in the USA compared with the general population over the period from 2000 to 2019. DESIGN/METHODS: Retrospective, longitudinal US population study of all deaths among people with epilepsy due to cardiovascular causes compared with the US general population for the years 2000 through 2019. Source data were obtained from the Centers for Disease Control and Prevention (CDC) Multiple Cause of Death Database using all International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for epilepsy (specifically all ICD-10 codes G40.0 through G40.919). The use of administrative datasets, like the CDC Multiple Cause Of Death Database, is a validated method that effectively captures US epilepsy mortality when using the ICD-10 codes G40.0-G40.9. Cardiovascular deaths were operationally defined as ischaemic heart disease, cerebrovascular disease, diabetes and hypertension. Data were stratified by age, race and gender. Relative proportions of each cause of death were expressed as a percentage of total deaths and evaluated on the log-odds scale using a logistic regression model. Standardised proportions were also used and reported. PRIMARY AND SECONDARY OUTCOMES: Within-group and between-group differences in the rate/proportions of deaths due to cerebrovascular disease, ischaemic heart disease, diabetes and hypertension among people with epilepsy and the general population over a 20-year period. SETTING: US epilepsy and general populations. RESULTS: Age-adjusted mortality for cerebrovascular disease and diabetes increased significantly among people with epilepsy compared with the US general population over the 20-year period (p<0.001). Age-stratified comparisons indicate that the proportions of deaths due to cerebrovascular disease and diabetes increased significantly among people with epilepsy compared with the general population aged 35-64 years. An unexpected finding is a trend reversal in the proportions of deaths from ischaemic heart disease among people with epilepsy. Prior to 2011, the proportion of deaths due to ischaemic heart disease among people with epilepsy declined steadily at a slope of -0.265 annually. After 2011, the slope changed from -0.265 to virtually zero in contrast to the continued decline in the US general population (epilepsy vs general population slope difference: p<0.001 after the breakpoint year). CONCLUSIONS: Age-standardised proportions of deaths attributed to cerebrovascular disease and diabetes increased significantly among people with epilepsy from 2000 to 2019. Age-stratified proportions of deaths due to cerebrovascular disease and diabetes occurred primarily in the 35-64-year age range. The long decline in the proportions of deaths due to ischaemic heart disease among people with epilepsy ended after 2011, despite continuing to decline in the general population. The increase in proportions of cardiovascular deaths among people with epilepsy is likely due to higher cardiovascular risk factors compared with the general US population. Increased surveillance and treatment of cardiovascular risk factors among people with epilepsy are indicated, especially in the critical 35-64-year age group, where improved primary prevention may reduce cardiovascular risk and mortality.