Identification of factors associated with new-onset vascular disease in patients admitted for video-EEG monitoring: A longitudinal cohort study

Abstract

Objective: People with epilepsy are at a higher risk of developing vascular disease. Understanding the risk factors in observational studies is hampered by the challenge in separating epilepsy-related risk and treatment-related risk, and uncertainty in the epilepsy diagnosis. This study aimed to identify factors associated with risk of subsequent vascular disease in patients with video-EEG monitoring (VEM) confirmed epilepsy.

Methods: We included patients with a diagnosis of epilepsy and nonepileptic disorders between January 1, 1995, and December 31, 2015. Incident cardiovascular, cerebrovascular, and peripheral vascular disease was determined by linkage to a state-wide hospital admissions database between 1st July 1994 and 28th February 2018. Incidence was compared with the general population.

Results: 1728 patients (59.7% female, median age 35 years) underwent VEM, and were followed up for a median of 9.2 years (range 2.2-22.9 years). Eight-hundred and thirty -two were diagnosed with epilepsy and 896 nonepileptic disorders. The incidence of cerebrovascular disease was higher in both patients with epilepsy (incidence rate ratio [IRR] 1.78, p = 0.001) and with nonepileptic disorders (IRR 1.61, p < 0.001) than in the general population. Patients who took valproic acid (VPA) were at a lower risk of vascular disease than those taking enzyme-inducing antiseizure medications (EIASM, subdistribution hazard ratio [SHR] 0.42, p = 0.013), and those taking neither VPA nor EIASM (SHR 0.47, p = 0.03). There was no difference in the incidence of vascular disease between patients with epilepsy and those without epilepsy (SHR 0.94, p = 0.766). Factors associated with increased risk included age (SHR 1.04, p < 0.001), male sex (SHR 1.50, p = 0.017), and smoking (SHR 1.68, p = 0.017).

Significance: In this study, both patients with epilepsy and without epilepsy had increased vascular risk. This suggests that the increased risk may be in part due to factors not directly related to epilepsy, such as EIASM use and vascular risk factors.

Keywords: Antiseizure medications; Cardiovascular disease; Epilepsy.