Targeted metabolomics profiles of ischemic stroke from two ethnic groups with different risk factors

Background— In the US, African Americans (AA) have a higher ischemic stroke and mortality rate than
Caucasians. Recent evidence suggests that the onset of an ischemic stroke may be related to circulating metabolite
alterations, contributing to racial disparities in ischemic stroke. The objective of this study was to determine whether
the metabolomic profile of African American ischemic stroke patients differs from that of Caucasian ischemic stroke
patients.
Methods— Metabolomic profiling of serum samples of 36 ischemic stroke (IS) patients (AA and Caucasian)
was carried out using ultrahigh performance liquid chromatography/mass spectrometry (UHPLC/MS) to measure
1062 known metabolites. Principal component analysis (PCA) was used to differentiate global metabolite profiles
for AA and Caucasian patients. A student T-test was used to compare scaled metabolite values between these two
groups. One-way ANOVA identified differences in identified metabolites among the African American Ischemic
stroke patients, Caucasian ischemic patients and control groups.
Results— A total of 13 metabolite levels were significantly different between the ischemic stroke and control group
for African Americans, while 86 metabolite levels were significantly different between the ischemic stroke patients
and control group including 36 being amino acids and 26 lipids. Of these, imidazoleacetic acid, N-acetylcysteine and
alpha-hydroxyisocaproate were significantly elevated in African American and Caucasian patients as compared to
controls. There was a statistically significant difference between African American and Caucasian ischemic stroke
patients [(F (2,26) = 7.101, p = 0.003)] for IAA. The level was highest in the control group (1.20 ± 0.41) compared
to the African American ischemic stroke patients (0.73 ± 0.38, p = 0.017) and lowest for Caucasian ischemic stroke
patients (0.67 ± 0.15, p = 0.010). Alpha-hydroxyisocaproate levels were significantly different between [(F (2,26)
= 7.193, p = 0.003)], and was highest for Caucasian IS patients (1.68 ± 0.89, p = 0.003), when compared with
the control group (0.83 ± 0.28, p=0.05) and African American ischemic stroke patients (1.31 ± 0.3, p = 0.096). In
addition, N-acetylcysteine levels were significant [(F (2,26) = 7.865, p = 0.002)], and were highest for the control
group (1.30 ± 0.50, p=0.004) compared to the African American (0.69 ± 0.26, p = 0.007) and the Caucasian ischemic
stroke patients (0.69 ± 0.35, p = 0.011).

Conclusions— Metabolomic profiles including imidazoleacetic acid, N-acetylcysteine and alpha-
hydroxyisocaproate significantly differed between African Americans and Caucasians ischemic stroke patients.

These race-associated alterations may contribute to racial disparities in the risk of ischemic stroke.