Abstract
BACKGROUND: Dyslipidemia is a well-established cause of atherosclerosis. Intraplaque neovascularization (IPN), a hallmark of vulnerable stroke-prone plaques, is a critical feature of dyslipidemia progression. However, the association between circulating lipid levels and IPN remains unclear. This study hypothesized that lipid ratios, particularly Castelli’s risk index-II (CRI-II; LDL-C/HDL-C), could function as biomarkers for IPN to help identify individuals at an elevated risk of ischemic stroke. METHODS: A total of 321 patients with carotid stenosis underwent contrast-enhanced ultrasound (CEUS) to assess the presence of IPNs. Patients were categorized into IPN-positive (n = 265) and IPN-negative (n = 56) groups. Standard lipid parameters (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C]) and derived ratios (non-HDL-C/HDL-C, CRI-I [TC/HDL-C], CRI-II [LDL-C/HDL-C]) were compared between the two groups. Multivariate logistic regression analysis identified the independent predictors of IPN. Receiver operating characteristic (ROC) curve analysis was conducted to establish the optimal predictive thresholds for significant lipid ratios. RESULTS: Multivariable regression identified smoking (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06–3.46; P = 0.031) and elevated CRI-II (OR 1.57, 95% CI 1.05–2.35; P = 0.028) as independent predictors of IPN. ROC analysis identified a CRI-II threshold of > 1.82 as optimal for predicting IPN, achieving a sensitivity of 74.3% and specificity of 46.4%. CONCLUSIONS: CRI-II is a novel and readily calculated serological biomarker of IPN. A value exceeding 1.82 can be used to identify patients with carotid stenosis harboring high-risk vulnerable plaques. It provides a widely accessible and cost-effective strategy for refining stroke risk assessment and offers the potential to enhance preventive care strategies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06315153. GRAPHICAL ABSTRACT: [Image: see text]