Multimodal ultrasound-based carotid plaque risk biomarkers predict poor functional outcome in patients with ischemic stroke or TIA

Abstract

Background: Carotid vulnerable plaque is an important risk factor for stroke occurrence and recurrence. However, the relationship between risk parameters related to carotid vulnerable plaque (plaque size, echogenicity, intraplaque neovascularization, and plaque stiffness) and neurological outcome after ischemic stroke or TIA is unclear. This study investigates the value of multimodal ultrasound-based carotid plaque risk biomarkers to predict poor short-term functional outcome after ischemic stroke or TIA.

Methods: This study was a single-center, prospective, continuous, cohort study to observe the occurrence of adverse functional outcomes (mRS 2-6/3-6) 90 days after ischemic stroke or TIA in patients, where the exposure factors in this study were carotid plaque ultrasound risk biomarkers and the risk factors were sex, age, disease history, and medication history. Patients with ischemic stroke or TIA (mRS ≤3) whose ipsilateral internal carotid artery stenosis was ≥50% within 30 days were included. All patients underwent multimodal ultrasound at baseline, including conventional ultrasound, superb microvascular imaging (SMI), and shear wave elastography (SWE). Continuous variables were divided into four groups at interquartile spacing for inclusion in univariate and multifactorial analyses. After completion of a baseline ultrasound, all patients were followed up at 90 days after ultrasound, and patient modified neurological function scores (mRSs) were recorded. Multivariate Cox regression and ROC curves were used to assess the risk factors and predictive power for predicting poor neurological function.

Results: SMI revealed that 20 (30.8%) patients showed extensive neovascularization in the carotid plaque, and 45 (69.2%) patients showed limited neovascularization in the carotid plaque. SWE imaging showed that the mean carotid plaque stiffness was 51.49 ± 18.34 kPa (23.19-111.39 kPa). After a mean follow-up of 90 ± 14 days, a total of 21 (32.3%) patients had a mRS of 2-6, and a total of 10 (15.4%) patients had a mRS of 3-6. Cox regression analysis showed that the level of intraplaque neovascularization and plaque stiffness were independent risk factors for a mRS of 2-6, and the level of intraplaque neovascularization was an independent risk factor for a mRS of 3-6. After correcting for confounders, the HR of intraplaque neovascularization level and plaque stiffness predicting a mRS 2-6 was 3.06 (95% CI 1.05-12.59, P = 0.041) and 0.51 (95% CI 0.31-0.83, P = 0.007), respectively; the HR of intraplaque neovascularization level predicting a mRS 3-6 was 6.11 (95% CI 1.19-31.45, P = 0.031). For ROC curve analysis, the mRSs for intraplaque neovascularization level, plaque stiffness, and combined application to predict 90-day neurological outcome ranged from 2 to 6, with AUCs of 0.73 (95% CI 0.59-0.87), 0.76 (95% CI 0.64-0.89) and 0.85 (95% CI 0.76-0.95), respectively. The mRSs for the intraplaque neovascularization level to predict 90-day neurological outcome ranged from 3 to 6, with AUCs of 0.79 (95% CI 0.63-0.95).

Conclusion: Intraplaque neovascularization level and plaque stiffness may be associated with an increased risk of poor short-term functional outcome after stroke in patients with recent anterior circulation ischemic stroke due to carotid atherosclerosis. The combined application of multiple parameters has efficacy in predicting poor short-term functional outcome after stroke.

Keywords: Carotid plaque; Multimodal ultrasound; Shear wave elastography; Stroke; Superb microvascular imaging.

Fig. 1

Images showing the distribution of neurological function scores after 90 days for different grades (limited, extensive) of the amount of neovascularization within the plaque

Fig. 2

Images showing plaque stiffness distribution for 90-day neurofunctional prognosis

Fig. 3

ROC curve analysis. A. Intraplaque neovascularization level, plaque stiffness and a combination of both predicted 90-day neurological outcome mRS score 2 to 6: IPN grade (blue line, AUC = 0.73), plaque stiffness (red line, AUC = 0.76) and combined application (green line, AUC = 0.85) ROC curves. The highest identification accuracy was achieved with the combined application, AUC = 0.85. B. Intraplaque neovascularization level predicts 90-day neurological outcome mRS score 3 to 6 with AUC 0.79. IPN = intraplaque neovascularization, PS = plaque hardness, AUC = area under the ROC curve, CI = confidence interval