2023 American Academy of Neurology Abstract Website

Objective:

Though uncontrolled diabetes leads to recurrent cardiovascular events in stroke survivors, many don’t achieve appropriate glycemic control. We hypothesize an adverse polygenic risk profile leads to worse glycemic control and higher risk of recurrent cardiovascular events in stroke survivors.

Background:

n/a

Design/Methods:

We conducted a population genetic study using data of stroke survivors enrolled in the UK Biobank and the Vitamin Intervention for Stroke Prevention (VISP) trial. In both studies, we modeled polygenic risk to diabetes through a polygenic risk score that included 462 single nucleotide polymorphisms known to associate with type 2 diabetes mellitus. Participants were stratified as low, intermediate, or high polygenic risk according to percentile values of this score (<20th, 20-80th and >80th percentile). We used multivariable linear, logistic, and Cox regression models to test for association between polygenic risk to diabetes and 1) hemoglobin A1c (HbA1c), 2) risk of treatment-resistant diabetes (HbA1c >7 despite pharmacological therapy), and 3) composite risk of recurrent stroke or coronary artery disease (CAD)

Results:

In 5,670 stroke survivors enrolled in the UK Biobank (mean age 61, 41% females), a higher polygenic risk to diabetes was associated with higher HbA1c in both participants with (Low=reference, Intermediate 0.23(.093), High 0.41(0.114)) and without diabetes (Low=reference, Intermediate 0.06(0.015), High 0.09(0.018)), and with higher risk of treatment-resistant diabetes (Low=reference, Intermediate 1.04(.98,1.11), High 1.12(1.04,1.21)). In 1,750 stroke survivors (mean age 68, 35% female 34) enrolled in VISP, a higher polygenic risk to diabetes was associated with higher composite risk of recurrent stroke or CAD ((Low=reference, Intermediate 1.11(0.78,1.57), High 1.53(1.03,2.28)). Beta (SE) or OR(95%CI)or HR(95%CI).

Conclusions:

Among stroke survivors, a higher polygenic risk to diabetes is associated with worse glycemic control and higher risk of recurrent vascular events. Further research is needed to evaluate the portability of these results to non-white individuals and identify effective therapies for patients with adverse genomic profiles.