Abstracts

Rationale: Stroke is the most common cause of epilepsy in older age implicated in 30-50% of cases, followed by epilepsy of unknown etiology that accounts for another 30-50% of cases. Cerebrovascular disease is also believed to underlie epilepsy in the cryptogenic group1,2. Recent population-based, epidemiological studies have addressed the role of specific vascular risk factors in the development of epilepsy with conflicting results3,4. We studied the role of potentially modifiable vascular risk factors in predicting subsequent epilepsy among participants aged 45 or older in the Framingham Heart Study (FHS), an ongoing, longitudinal, community-based study that began in 1948.  Methods: In 1971, the offspring of the original participants and their spouses (n=5,124) were enrolled in the Offspring Cohort and participants have been attending surveillance exams every 4 years. In this cohort, we used a vigorous method for adjudication of epilepsy cases that included review of the participants' medical charts in order to exclude seizure mimics (syncope etc) and acute symptomatic seizures. The vascular risk factors studied included hypertension (HTN), diabetes mellitus, smoking, and hyperlipidemia. The role of prevalent cardiovascular disease (CVD) and atrial fibrillation (AF) was also investigated. Cox proportional hazards regression models were used for the analysis. Results: Participants of the Offspring cohort who attended FHS exam 5 (1991-1995), 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) were included in the analysis. Fifty-five incident epilepsy cases were identified during follow-up that ranged between 1 and 25 years (mean 19.2, SD5.7). Hypertension, defined as systolic blood pressure >=140mmHg and/or diastolic blood pressure >=90mmHg or use of anti-hypertensive medications, was associated with a near 2-fold risk (HR 1.97, 95%CI [1.13,3.45], p= 0.017) of developing epilepsy even after adjustment for prevalent stroke. In secondary analysis, excluding patients receiving anti-HTN treatment (n= 2,613, 50 incident epilepsy cases) the association was even stronger (HR 2.44, 95%CI [1.36,4.35], p=0.003). Prevalent CVD and AF affected 12% and 2% of participants, respectively, and although there was a trend towards a positive association with epilepsy, neither reached statistical significance.  Conclusions: Our results offer further evidence that hypertension, a vascular risk factor which is highly prevalent in the general population, increases 2.5-fold the risk of developing epilepsy in older age, even in the absence of a clinical stroke. Our results show that this risk is modifiable and may decrease with treatment of HTN. 1. Li X, Breteler MM, de Bruyne MC, Meinardi H, Hauser WA, Hofman A. Vascular determinants of epilepsy: the Rotterdam Study. Epilepsia 1997;38:1216-20.2. Cleary P, Shorvon S, Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet 2004;363:1184-6.3. Johnson EL, Krauss GL, Lee AK, et al. Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study. JAMA Neurol 2018;75:1375-82.4. Choi H, Pack A, Elkind MS, Longstreth WT, Jr., Ton TG, Onchiri F. Predictors of incident epilepsy in older adults: The Cardiovascular Health Study. Neurology 2017;88:870-7 Funding: FACES