Carotid Artery Plaque Echomorphology and its Association with Histopathological Characteristics May Predict Symptomatic Disease

Abstract

Introduction - A number of ultrasonic texture features which include severity of stenosis, grey scale median (GSM), plaque area (PA), juxtaluminal plaque area (JBA) and discrete white area (DWA) have been shown to be independent predictors of future strokes in carotid disease patients. The primary aim of the present study was to determine the association between histological features and ultrasonic plaque texture features after carotid endarterectomy. Secondary aim was to assess the association between statin therapy and symptomatic disease or other histological features. Methods - B-mode ultrasound images of carotid plaques were obtained during preoperative scanning and texture measurements were made using commercially available software (LifeQ Medical). Histological transverse plaque sections of the most severe stenotic site were graded 0-3 for the number of macrophages (CD68 staining), severity of angiogenesis (CD31 staining), smooth muscle cell numbers (SMC) and size of lipid core; and 0 or 1 for thickness of fibrous cap, presence of intraplaque haemorrhage (IPH), plaque rupture and instability. Demographics, co-morbidities, statin therapy and total cholesterol level were also recorded. Multivariable logistic regression models of symptoms as the dependent variable and of histological features (model a) and ultrasonic features (model b) as the independent variables were undertaken. Results - B-mode ultrasound images (mean stenosis of 86%; range 60-99%) from 70 consecutive patients (20 symptomatic and 50 asymptomatic) were obtained. The presence of CD 68 was correlated with lower values of GSM (p=0.001) and presence of DWA (p=0.001). Increased number of SMCs was associated with higher values of GSM (p=0.003), lower DWA (p=0.003) and JBA (p=0.042) and lower degree of stenosis (p=0.025). Presence of CD 31 was associated with lower values of GSM (p=0.003) and presence of DWA (p<0.001). Larger lipid core and unstable plaques were associated with lower values of GSM (p=0.001; p=0.002 respectively), presence of DWA (p=0.025; p=0.027 respectively) and JBA (0.0013; p=0.006 respectively). Statin therapy after being adjusted for symptoms, was associated with lower percentage of CD 68 (OR: 0.17; 95% confidence interval [CI]: 0.04 to 0.73; P=0.038), lower degree of CD 31 (OR: 0.17; CI 0.04 to 0.75, p= 0.019) and higher percentage of SMCs (OR: 6.02; CI: 1.28 to 28.1, p= 0.023). In model (a) the presence of CD68, SMCs and intraplaque hemorrhage were independent predictors of symptomatic plaques. [ROC Area under the curve: 0.870; 95% CI 0.767 to 0.973. (85.7 % correct classification of plaques into symptomatic or asymptomatic for a cut value of 0.50 probability)]. In model (b) the presence of DWA and JBA were independent predictors of symptomatic plaques [ ROC Area under the curve: 0.701; 95% CI 0.562 to 0.840. (76.7 % correct classification of plaques into symptomatic or asymptomatic for a cut value of 0.50 probability)]. Conclusion - The presence of markers indicative of inflammation and neo-angiogenesis as histopathologic plaque characteristics are associated with unstable carotid atheroma based on ultrasonic analysis. Histological features such as CD68, SMCs and intraplaque hemorrhage and ultrasonic features such as DWA and JBAmay be predictors of symptomatic plaques.