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Background: Intra-plaque hemorrhage in carotid atheromatous plaque is a recognized high-risk state for ische‐ mic events. Intra-plaque neovascularization can now be visualized by contrast-enhanced carotid ultrasonography (CEUS). These neovessels appear prone to rupture and may be a marker for high-risk of intra-plaque hemor‐ rhage. This study aimed to investigate relationships among circulating biomarkers associated with carotid pla‐ que instability and the presence of intra-plaque hemorrhage on magnetic resonance imaging (MRI) and intraplaque neovascularization on CEUS in patients with advanced atherosclerotic plaques. Methods: Fifty-one patients with mild to severe carotid stenosis were prospectively enrolled, and carotid ultra‐ sonography, CEUS, and MRI were performed. Circulating levels of soluble lectin-like oxidized low-density lip‐ oprotein receptor-1 (sLOX-1), pentraxin 3 (PTX3), myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, and high-sensitivityC-reactive protein (hs-CRP) were also measured. Results: Carotid plaques were categorized into 3 groups based on MRI findings: fibrous tissue, n=13; lipid/ necrotic core, n=30; and intra-plaque hemorrhage, n=8. Regarding plaque echogenicity, 24 plaques were hypoe‐ choic, and 27 were non-hypoechoic. Intra-plaque neovascularization on CEUS was observed in 14 plaques. Multivariate logistic regression analysis identified hypoechoic plaque (odds ratio, 63.126; 95% confidence inter‐ val, 1.102–3616.91) and serum hs-CRP (1.064; 1.002–1.130) as factors significantly associated with intra-pla‐ que hemorrhage. Hypoechoic plaque (30.362; 2.462–374.37), and serum hs-CRP (1.066; 1.003–1.132) were re‐ vealed as factors significantly associated with intra-plaque neovascularization. Conclusions: Hypoechoic plaque and hs-CRP levels were identified as common predictors of intra-plaque hem‐ orrhage and intra-plaque neovascularization. Longitudinal studies are warranted to clarify the roles of intra-pla‐ que neovascularization on CEUS and hs-CRP levels in intra-plaque hemorrhage and ischemic stroke.

journal of st. marianna university

Circulating Levels of High-sensitivity C-reactive protein are Associated with Intra-plaque Neovascularization and Intra-plaque Hemorrhage as Evaluated by Contrast-enhanced Ultrasonography and Magnetic Resonance Imaging