Literature Review

Hypertension may double the risk of late-onset epilepsy



Hypertension is associated with more than a twofold increased risk of developing late-onset epilepsy even in patients who have not had a previous stroke, new research suggests.

After excluding individuals with normal blood pressure who were taking antihypertensive medication, investigators found hypertension was linked to an almost 2.5-fold higher risk of epilepsy.

“Our findings further expand upon our knowledge of the negative effects hypertension has on brain health and, regarding epilepsy, that effect may be starting even in midlife,” said co–lead author Maria Stefanidou, MD, MSc, of Boston University.

“Practicing clinicians should be vigilant to diagnose hypertension, discuss with patients all potential long-term brain health outcomes, and need for treatment. Furthermore, in those presenting with new-onset epilepsy later in life, screening for potentially undiagnosed hypertension should be included in the initial workup,” she said.

The study was published online Nov. 17, 2021, in Epilepsia.

Unknown etiology

“New-onset epilepsy risk increases with increasing age over the age of 65 and can affect 15-20 per 1,000 older individuals. Although the most common causes for seizures in this age group are prior history of stroke and presence of dementia, for about 30%-40% of patients, the etiology of seizures remains unknown,” Dr. Stefanidou said.

“We wanted to study if modifiable vascular risk factors that are known to contribute both to vascular brain aging and to neurodegeneration may directly predict the development of epilepsy, even in the absence of clinical stroke or dementia,” she added.

To investigate, the researchers turned to data from participants in the Offspring Cohort of the Framingham Health Study (FHS). The original FHS was an ongoing longitudinal community-based study that first began in 1948. Offspring of the original cohort and their spouses (n = 5,124) were enrolled in the Offspring Cohort in 1971, with surveillance of these second-generation participants based on exam visits occurring every 4 years.

The study included participants who had attended exam 5 (1991-1995), were age 45 years or older, had available vascular risk factor (VRF) data, and available follow-up data on epilepsy status (n = 2,986; mean age, 58 years; 48% male).

The investigators conducted two statistical analyses. In the primary model, they adjusted for age and gender, while in a secondary model they also adjusted for prevalent and interim stroke. They also conducted an analysis that excluded participants treated with antihypertensive medication and had normal blood pressure.

Plausible mechanisms

During a mean follow-up of 19.2 years, 55 incident epilepsy cases were identified. The mean age of these patients was 73.8 years.

In the primary model, hypertension was associated with an almost twofold higher risk of developing epilepsy (hazard ratio, 1.97; 95% confidence interval, 1.13-3.45; P = .017).

Interestingly, the Framingham Stroke Risk Profile – a calculation based on an array of factors, including age/sex, systolic blood pressure, antihypertensive therapy, diabetes, history of cardiovascular disease, atrial fibrillation, and cigarette smoking – was not associated with incident epilepsy, and there was no other significant associated between any of the other VRFs when looked at independently.

When the researchers adjusted for prevalent and interim stroke, they continued to find an almost twofold higher risk of developing epilepsy (HR 1.93; 95% CI, 1.10-3.37; P = .022). An analysis that adjusted for competing risk of death obtained similar findings (HR, 1.98; 95% CI, 1.03-3.81; P = .042).

The model that excluded patients receiving antihypertensive treatment, whose blood pressure readings were normal (n = 2,162; 50 incident epilepsy cases) showed an even stronger association (HR, 2.44; 95% CI, 1.36-4.35; P = .003).

“Our results are based on an epidemiological, observational study, therefore our findings point to an association between hypertension and new-onset epilepsy later in life,” said Dr. Stefanidou.

She noted that because it was an observational study, “a cause-effect relationship cannot be established based on these results, but there is growing evidence from our, as well as other, similar cohorts that hypertension, a modifiable vascular risk factor, may indeed be an independent predictor of late-onset epilepsy.”

There are “plausible mechanisms” that support both a direct, and indirect, role of hypertension – for example, through accumulation of small vessel disease in the brain – but further research will be necessary to elucidate the exact mechanisms involved in the process,” she added.


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