Epigenetic Clock Analysis for National Institutes of Health Stroke Scale in Patients With Ischemic Stroke

Strokes are the second most common cause of mortality and disability worldwide. Ischemic strokes account for the main part of strokes. Recently, the epigenetic changes that occur during biological aging through DNA methylation have gained attention. The National Institutes of Health Stroke Scale (NIHSS) scores measure physical and cognitive function. We hypothesized that there are associations between acute changes in the NIHSS score and biological aging in patients with ischemic stroke. We conducted epigenetic clock analyses to investigate the association between the difference in NIHSS (dNIHSS) and epigenetic clock in patients with ischemic stroke.

We used two publicly available DNA methylation data sets from Caucasian patients with ischemic stroke in Spain. The discovery data set consists of 59 patients with ischemic stroke, and the replication dataset consists of 62. Acceleration of several epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, GrimAge2, DNA methylation-based telomere length, and DunedinPACE), GrimAge components, and GrimAge2 components was analyzed with standard multiple regression analyses with dNIHSS. We obtained information on dNIHSS between discharge and baseline for each patient. We integrated these results from the two data sets using meta-analyses.

There was no significant association in the epigenetic age acceleration. The predictive value of only Cystatin C showed a significant association with dNIHSS in the GrimAge components.

We could not find a significant association between the severity during the acute phase of ischemic stroke and epigenetic clocks. We may be able to find different findings with a larger sample size and longitudinal data such as NIHSS scores at fixed intervals.