Carotid intraplaque neovascularization assessed by AngioPLUS is an independent predictor of recurrent anterior circulation ischemic stroke, and a parsimonious Cox model incorporating IPN Grade 2 and LDL-C demonstrated favorable discrimination and calibration for identifying high-risk patients.
Key Findings
Results
The recurrence rate of ischemic stroke was significantly higher in the high IPN group compared to the low IPN group.
Recurrence rate was 35.0% in the high IPN group versus 6.0% in the low IPN group (p < 0.001).
143 consecutive patients with anterior circulation ischemic stroke (ACIS) were prospectively enrolled between August 2020 and February 2025.
26 patients experienced recurrent ischemic stroke over a median follow-up of 21 months (range 6–56 months).
The cohort was 65.0% male with a mean age of 67.6 ± 11.7 years.
Results
Lasso regression identified IPN Grade 2 and LDL-C as the two core independent predictors of recurrent ischemic stroke.
IPN Grade 2 had a hazard ratio of 5.30 (95% CI 1.99–14.08, p < 0.001).
LDL-C had a hazard ratio of 2.23 (95% CI 1.41–3.52, p < 0.001).
Least absolute shrinkage and selection operator (Lasso) regression was used to screen core predictors from among all candidate variables identified by Cox proportional hazards regression.
These two predictors were incorporated into a parsimonious Cox model.
Results
The parsimonious prediction model demonstrated favorable discrimination with a C-index of 0.786.
The concordance index (C-index) was 0.786 (95% CI 0.707–0.866).
Internal validation was performed using Bootstrap resampling with B = 1000 iterations.
Time-dependent AUC values were 0.716, 0.809, and 0.815 at 12, 24, and 36 months, respectively.
Calibration plots closely approximated the ideal diagonal line, indicating good model calibration.
Results
Nomogram-based risk stratification revealed significantly lower recurrence-free survival rates in the high-risk group compared to the low-risk group.
Recurrence-free survival rates in the high-risk group were 80.46%, 36.40%, and 28.31% at 12, 24, and 36 months, respectively.
Recurrence-free survival rates in the low-risk group were 97.73%, 90.80%, and 88.21% at 12, 24, and 36 months, respectively.
The median survival time was 23.0 months in the high-risk group and was not reached in the low-risk group (log-rank p < 0.001).
Risk stratification was conducted based on the optimal cut-off value of the total nomogram score.
Differences in survival between groups were compared using the Kaplan-Meier method and the log-rank test.
Methods
AngioPLUS ultrasound was used as the novel imaging technique for assessing carotid intraplaque neovascularization (IPN) in this prospective cohort.
Consecutive patients admitted for ACIS who underwent IPN assessment using AngioPLUS ultrasound were prospectively enrolled.
IPN was graded, with Grade 2 identified as a significant predictor in the final model.
The study enrolled patients over a period spanning August 2020 to February 2025.
The predictive value of AngioPLUS-derived IPN for recurrent ACIS had not been previously established.
What This Means
This research suggests that a specialized ultrasound technique called AngioPLUS can detect tiny new blood vessels growing inside carotid artery plaques (the fatty deposits that build up in arteries in the neck), and that the presence of these vessels can predict whether a stroke patient is likely to have another stroke. In a study of 143 stroke patients followed for nearly two years on average, those with more prominent intraplaque neovascularization had a stroke recurrence rate of 35%, compared to only 6% in those with less neovascularization. By combining this ultrasound measure with a standard blood test for LDL cholesterol ('bad' cholesterol), the researchers built a scoring tool (nomogram) that predicted who would have a second stroke with good accuracy.
The prediction model was validated using a rigorous statistical method (bootstrap resampling) and showed strong performance over 1, 2, and 3 years of follow-up. Patients classified as high-risk by the nomogram had dramatically lower stroke-free survival — fewer than 30% remained stroke-free at 3 years, compared to over 88% of those classified as low-risk. The model's calibration (how well predicted risks matched actual outcomes) was also found to be good.
This research suggests that routinely assessing carotid plaque vascularity using AngioPLUS ultrasound, alongside LDL cholesterol levels, could help doctors identify which stroke survivors face the greatest risk of a recurrence and may benefit most from more intensive preventive treatment. The tool is described as simple and practical for use in clinical settings, potentially enabling more personalized secondary stroke prevention strategies.
Zhang H, He J, Xu J, Wang R, Cao S, Xia M. (2026). AngioPLUS-derived carotid intraplaque neovascularization predicts recurrent anterior circulation stroke: a prospective cohort study.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1819400