Identification of Metabolomics Biomarkers in Extracranial Carotid Artery Stenosis

Abstract

The biochemical identification of carotid artery stenosis (CAS) is still a challenge. Hence, 349 male subjects (176 normal controls and 173 stroke patients with extracranial CAS ≥ 50% diameter stenosis) were recruited. Blood samples were collected 14 days after stroke onset with no acute illness. Carotid plaque score (≥2, ≥5 and ≥8) was used to define CAS severity. Serum metabolites were analyzed using a targeted Absolute IDQ®p180 kit. Results showed hypertension, diabetes, smoking, and alcohol consumption were more common, but levels of diastolic blood pressure, HDL-C, LDL-C, and cholesterol were lower in CAS patients than controls (p < 0.05), suggesting intensive medical treatment for CAS. PCA and PLS-DA did not demonstrate clear separation between controls and CAS patients. Decision tree and random forest showed that acylcarnitine species (C4, C14:1, C18), amino acids and biogenic amines (SDMA), and glycerophospholipids (PC aa C36:6, PC ae C34:3) contributed to the prediction of CAS. Metabolite panel analysis showed high specificity (0.923 ± 0.081, 0.906 ± 0.086 and 0.881 ± 0.109) but low sensitivity (0.230 ± 0.166, 0.240 ± 0.176 and 0.271 ± 0.169) in the detection of CAS (≥2, ≥5 and ≥8, respectively). The present study suggests that metabolomics profiles could help in differentiating between controls and CAS patients and in monitoring the progression of CAS.