Abstract

Introduction: Extensive neovascularization in atherosclerotic plaque has been shown to be associated with plaque progression and instability, leading to atherosclerotic cardiovascular events. Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization. Hypothesis: Assessment of intra-plaque neovascularization of the carotid artery using quantitative analysis of CEUS provides prognostic information in patients with coronary artery disease (CAD). Methods: This study included 206 patients with stable CAD and with carotid intima-media thickness (IMT) > 1.1 mm. They underwent a CEUS examination of the carotid artery and were followed-up prospectively for < 38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction [MI], unstable angina pectoris [uAP] requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque after the intravenous injection of contrast material was quantified by calculating the increase in mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. Results: During the follow-up period (3 - 38 months, mean 22.8 ± 11.8 months), 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazards analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.52; 95% CI, 1.20 - 1.94; p = 0.001). The addition of plaque enhanced intensity had a significant incremental effect on the area under the ROC curve (AUC) generated using baseline model of traditional risk factors (AUC: baseline model 0.69 vs. baseline model + plaque enhanced intensity 0.78, p = 0.03). The addition of the plaque enhanced intensity to the baseline risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58, p = 0.003; and IDI 0.078, p = 0.03). Conclusions: The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.

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