Abstract
BACKGROUND: The pathogenesis of ischemic stroke is multifaceted, and growing evidence highlights that mixed etiologies should be considered. This prospective cohort study investigated the relationship between plasma levels of trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor, and etiologic stroke subtypes. METHODS: Plasma TMAO levels were compared in 223 patients, including 95, 73, and 55 patients with large artery atherosclerosis (LAA), cardioembolism (CE), and cardioembolism with culprit artery stenosis (CES), respectively, admitted with acute ischemic stroke complicated by large vessel occlusion and treated with endovascular therapy. At-admission clinical data and blood samples obtained during intervention were collected. RESULTS: After adjusting for covariates, including age, sex, hypertension, diabetes mellitus, estimated glomerular filtration rate(eGFR), smoking, and alcohol consumption, plasma TMAO levels were highest in the CES group (1.583 μmol/L), followed by the LAA and CE groups (1.064 and 0.583 μmol/L, respectively), with significant differences among the three groups detected (Wald χ(2) = 22.877, p < 0.001). By binary logistic regression analysis after adjusting for the same covariates, plasma TMAO level was an independent predictor for distinguishing the CES subtype from the CE subtype (95% CI, 2.062-8.183; p < 0.001), with an area under the curve of 0.778. CONCLUSION: Plasma TMAO levels, which were highest in patients with stroke due to CES, followed by those with stroke due to LAA and CE, may serve as an independent predictor for distinguishing CE from CES as the stroke etiology.