Carotid plaque characteristics in the CREST-2 trial

Abstract

Background

The modest stroke prevention from surgery for asymptomatic carotid disease has prompted a search for predictors that may improve risk stratification beyond luminal stenosis. Plaque disruption and atheroembolization are associated with unique anatomical and histological changes. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) collects information on duplex ultrasound (DUS) plaque biomarkers with the goal of evaluating their relationship to the periprocedural and long-term risks of stroke. In this study, we examine the reliability with which carotid plaque features can be measured from DUS images, and report baseline carotid DUS-derived stenosis and plaque features using semiautomated digital image analysis of patients enrolled in CREST-2.

Methods

We studied the first 503 patients in CREST-2. Patients underwent standardized carotid DUS evaluation pre-enrollment. B-Mode images were scaled linearly to normalize brightness. Plaques were outlined manually. Dedicated software automatically measured the longitudinal sectional area (mm²), grayscale median (GSM), Gray-Weale classification, and tissue composition (mm²) of intraplaque hemorrhage (IPH), lipid, fibrous tissue, muscle, and calcium. We present the mean, standard deviation, median, interquartile range, minimum and maximum range, and proportions of carotid peak systolic velocities (PSVs) and plaque morphological features. We tested for autocorrelation among plaque features and computed the proportion of potentially unstable plaques in the cohort. Reliability of the image analysis techniques was tested in 100 patients using Bland-Altman plots and intraclass and interclass correlation coefficients.

Results

Most patients were male (58.4%), older (mean age of 69.3 years), White (87.5%), and had a PSV of ≥230 cm/s (98.6%); the 1.4% with a PSV of <230 cm/s were enrolled based on catheter angiography. Plaques in this study were large; the mean longitudinal sectional area was 62 ± 37 mm² (range, 6.2–256.5 mm²). The mean GSM was 58 ± 30 (unitless) (range, 0–168) and Gray-Weale classification was 3.5 ± 0.9 (range, 1–5). The mean areas of tissue types were IPH 5.3 ± 8.9 mm², lipid 9.3 ± 8.6 mm², fibrous tissue 10 ± 10 mm², muscle 17 ± 12 mm², and calcium 1.6 ± 4.1 mm². The PSV of patients showed poor correlation with plaque features. The proportion of plaques with a GSM of ≤35 was 22.8%, IPH of ≥5 mm² was 30.0%, and a lipid-rich necrotic core of ≥40% was 3.0% of the cohort. Plaque measurements could be performed with high reliability with good interobserver and intraobserver correlations.

Conclusions

Site-generated, core laboratory-interpreted ultrasound examination provides a reliable way of characterizing carotid plaque morphological features across studies performed at many CREST-2 sites. The initial cohort of patients randomized in CREST-2 had heterogeneity of plaque features despite causing high-grade stenosis. Completion of the trial will provide an opportunity to assess whether plaque heterogeneity interacts with response to revascularization and medical management.