Vascular risk factors as predictors of epilepsy in older age: The Framingham Heart Study

Maria Stefanidou*, Jayandra J. Himali, Orrin Devinsky, Jose R. Romero, Mohammad Arfan Ikram, Alexa S. Beiser, Sudha Seshadri, Daniel Friedman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)


Objective: Stroke is the most common cause of epilepsy in older age. Subclinical cerebrovascular disease is believed to underlie some of the 30%–50% of late-onset epilepsy without a known cause (Li et al. Epilepsia. 1997;38:1216; Cleary et al. Lancet. 2004;363:1184). We studied the role of modifiable vascular risk factors in predicting subsequent epilepsy among participants ages 45 or older in the Framingham Heart Study (FHS), a longitudinal, community-based study. Methods: Participants of the Offspring Cohort who attended FHS exam 5 (1991–1995) were included who were at least 45-years-old at that time, had available vascular risk factor data, and epilepsy follow-up (n = 2986, mean age 58, 48% male). Adjudication of epilepsy cases included review of medical charts to exclude seizure mimics and acute symptomatic seizures. The vascular risk factors studied included hypertension, diabetes mellitus, smoking, and hyperlipidemia. The role of the Framingham Stroke Risk Profile score was also investigated. Cox proportional hazards regression models were used for the analyses. Results: Fifty-five incident epilepsy cases were identified during a mean of 19 years of follow-up. Hypertension was associated with a near 2-fold risk (hazard ratio [HR]: 1.93, 95% confidence interval [CI]: 1.10–3.37, p =.022) of developing epilepsy, even after adjustment for prevalent and interim stroke. In secondary analysis, excluding patients with normal blood pressure who were receiving anti-HTN (anti-hypertensive) treatment (n = 2613, 50 incident epilepsy cases) the association was (HR: 2.44, 95% CI: 1.36–4.35, p =.003). Significance: Our results offer further evidence that hypertension, a potentially modifiable and highly prevalent vascular risk factor in the general population, increases 2- to 2.5-fold the risk of developing late-onset epilepsy.

Original languageEnglish
Pages (from-to)237-243
Number of pages7
Issue number1
Publication statusPublished - Jan 2022

Bibliographical note

Funding Information:
This study was feasible through grant support from the National Institutes of Health (NIH) R01AG054076‐02 and Finding a Cure for Epilepsy/Seizures (FACES) to SS and MS.

Publisher Copyright:
© 2021 International League Against Epilepsy


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