Abstract
INTRODUCTION: Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks. METHODS: Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios. RESULTS: We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509-0.717), 0.833(95% CI:0.755-0.911), and 0.843(95% CI:0.777-0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p<0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score. CONCLUSION: We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.