{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:31:52Z","timestamp":1786422712966,"version":"build-2736575974"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>The predictive value of carotid intraplaque neovascularization (IPN), assessed by the novel AngioPLUS technique, for recurrent anterior circulation ischemic stroke (ACIS) remains unclear. This study aimed to evaluate the prognostic value of IPN for stroke recurrence in patients with ACIS and to develop a parsimonious prediction model by screening core predictors using Lasso regression, with subsequent assessment of its discrimination, calibration, and clinical utility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Consecutive patients admitted for ACIS who underwent IPN assessment using AngioPLUS ultrasound between August 2020 and February 2025 were prospectively enrolled. Independent predictors of recurrent ischemic stroke were identified using Cox proportional hazards regression models. Least absolute shrinkage and selection operator (Lasso) regression was employed to screen core predictors for constructing a parsimonious Cox model. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) curves, and internal validation was performed with Bootstrap resampling\n                      <jats:inline-formula>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                          <mml:mi>B<\/mml:mi>\n                          <mml:mo>=<\/mml:mo>\n                          <mml:mn>1000<\/mml:mn>\n                        <\/mml:math>\n                      <\/jats:inline-formula>\n                      to calculate the concordance index (C-index). Model calibration was assessed using calibration plots. Risk stratification was conducted based on the optimal cut-off value of the total nomogram score, and differences in survival between groups were compared using the Kaplan\u2013Meier method and the log-rank test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 143 patients (93 males, 65.0%; mean age 67.6\u202f\u00b1\u202f11.7\u202fyears) with a median follow-up of 21\u202fmonths (range 6\u201356\u202fmonths) were enrolled, during which 26 patients experienced recurrent ischemic stroke. The recurrence rate was significantly higher in the high IPN group compared to the low IPN group (35.0% vs. 6.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Lasso regression identified two core predictors: IPN Grades 2 (HR\u202f=\u202f5.30, 95% CI 1.99\u201314.08,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) and LDL-C (HR\u202f=\u202f2.23, 95% CI 1.41\u20133.52,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). The parsimonious model yielded a concordance index (C-index) of 0.786 (95% CI 0.707\u20130.866), with time-dependent AUC values of 0.716, 0.809, and 0.815 at 12, 24, and 36\u202fmonths, respectively. Calibration plots closely approximated the ideal diagonal line. Nomogram-based risk stratification demonstrated that patients in the high-risk group had significantly lower recurrence-free survival rates at 12, 24, and 36\u202fmonths (80.46, 36.40, and 28.31%, respectively) compared to those in the low-risk group (97.73, 90.80, and 88.21%, respectively). The median survival time was 23.0\u202fmonths in the high-risk group and was not reached in the low-risk group (log-rank\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Carotid IPN is an independent predictor of ACIS recurrence. A parsimonious Cox model incorporating IPN Grades 2 and LDL-C demonstrated favorable discrimination and calibration. The nomogram based on this model effectively identifies individuals at high risk of recurrence, offering a simple and practical tool for guiding individualized secondary prevention strategies in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1819400","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:21:26Z","timestamp":1786422086000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["AngioPLUS-derived carotid intraplaque neovascularization predicts recurrent anterior circulation stroke: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shugang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, The Second People's Hospital of Hefei","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/MAJ.0b013e31815b60a1","article-title":"The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke","volume":"336","author":"Ding","year":"2008","journal-title":"Am J Med Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.jacl.2019.07.008","article-title":"Rapid improvement in carotid adventitial angiogenesis and plaque neovascularization after rosuvastatin therapy in statin treatment-na\u00efve subjects","volume":"13","author":"Du","year":"2019","journal-title":"J Clin Lipidol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"635","DOI":"10.2459\/JCM.0b013e3283590cd2","article-title":"Intraplaque neovascularization and hemorrhage: markers for cardiovascular risk stratification and therapeutic monitoring","volume":"13","author":"Koole","year":"2012","journal-title":"J Cardiovasc Med (Hagerstown)"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1002\/jum.14602","article-title":"Comparison of the diagnostic performance of power Doppler ultrasound and a new microvascular Doppler ultrasound technique (AngioPLUS) for differentiating benign and malignant breast masses","volume":"37","author":"Jung","year":"2018","journal-title":"J Ultrasound 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Health"},{"key":"ref17","first-page":"676","article-title":"Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology","volume":"29","author":"Gray-Weale","year":"1988","journal-title":"J Cardiovasc Surg"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12883-023-03052-6","article-title":"Multimodal ultrasound-based carotid plaque risk biomarkers predict poor functional outcome in patients with ischemic stroke or TIA","volume":"23","author":"Cheng","year":"2023","journal-title":"BMC Neurol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4815","DOI":"10.21037\/qims-24-202","article-title":"Intraplaque neovascularization combined with plaque elasticity for predicting ipsilateral stroke in patients with asymptomatic mild carotid stenosis","volume":"14","author":"Zhang","year":"2024","journal-title":"Quant Imaging Med Surg"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/acn3.52255","article-title":"Incremental clinical value of intraplaque neovascularization in predicting recurrent ischemic stroke","volume":"12","author":"Cui","year":"2025","journal-title":"Ann Clin Transl Neurol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12944-025-02821-1","article-title":"The lipid ratio Castelli's risk index II is a novel biomarker for intraplaque neovascularization in patients with carotid stenosis","volume":"25","author":"Cui","year":"2025","journal-title":"Lipids Health Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1442656","DOI":"10.3389\/fneur.2024.1442656","article-title":"Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque","volume":"15","author":"Liu","year":"2024","journal-title":"Front 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