Study on the correlation between carotid plaque calcification types and the recurrence of ischemic stroke

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In addition, conjoint analysis was conducted to explore the physical activity, appetite, sleep and mood of the patients as variables, in order to provide new reference for the clinical treatment and management of ischemic stroke. Method: Patients who underwent head and neck CTA scans and who were diagnosed with unilateral or bilateral carotid plaques with stenosis < 70% at the First People’s Hospital of Lianyungang from September 2022 to August 2023 were enrolled in this study, with 2–3 years of follow-up. Patients meeting the inclusion criteria were classified into 1–6 types based on plaque calcification characteristics, in order to analyze differences in recurrent stroke between these types. Results: Using on the inclusion and exclusion criteria, 346 patients with carotid plaque were included. In the clinical baseline data, no statistically significant differences were observed between the recurrent and the non-recurrent stroke groups. Spearman’s correlation analysis revealed statistically significant associations between plaque calcification types and recurrent stroke (p < 0.001). Subsequently, Cox proportional hazards model analysis further demonstrated a significant correlation between plaque calcification types and clinical endpoint (HR: 1.149,95% CI: 1.059–1.247, p < 0.001). Even after adjusting for sleep, appetite, physical activity and mood of the patients, the plaque calcification types remained significantly associated with the clinical endpoint (HR: 1.128,95% CI: 1.037–1.226, p = 0.005). Conclusion: This study indicates a correlation between carotid plaque calcification types and the recurrence of stroke. These findings provide a new approach to studying carotid atherosclerotic plaque calcification and further imaging-based evidence for the risk assessment of recurrent ischemic stroke. atherosclerosis carotid plaque calcified plaque recurrent stroke Figures Figure 1 Figure 2 Figure 3 Introduction Stroke is the leading cause of death and disability worldwide, and stroke recurrence is associated with a heightened risk of recurrence or death within five years after the first stroke [ 1 ] . In addition, recurrent ischemic strokes often cause more severe cerebrovascular damage and cognitive impairment than the first stroke. Patients with carotid atherosclerosis (AS) plaques have a significantly increased risk of recurrent cerebrovascular events, and they are a major contributor to ischemic stroke [ 2 ] . The primary underlying cause of ischemic stroke in these patients is the rupture of vulnerable carotid plaques, which may trigger thrombosis and embolism, ultimately blocking downstream vessels. In addition, calcification is commonly observed in atherosclerotic plaques, and it typically develops during the progression of atherosclerotic lesions, although its exact mechanisms remain unclear. Apoptotic cells, extracellular matrix, and necrotic core material can serve as precursors for microscopic calcium deposits, which may further coalesce into larger calcified plaques [ 3 ] . However, the current research on calcified plaques remains controversial, as the impact of calcification with different sizes and morphologies on cerebrovascular events shows variable results. Moreover, existing studies predominantly focus on a single calcification feature rather than comprehensive analysis. In contrast, this study comprehensively investigated the size, location, and shape characteristics of plaque calcification, following the 6-type classification proposed by Saba L [ 4 ] , as follows: Type 1: complete absence of calcification within the plaque; Type 2: intimal or superficial calcifications; Type 3: deep or bulky calcifications; Type 4: adventitial calcifications with internal soft plaque of < 2 mm thickness (negative rim sign); Type 5: mixed patterns with intimal and bulky calcifications; and Type 6: positive rim sign. For stroke patients, it is critical to equally monitor their physical activity, appetite, sleep, and mood following stroke onset. In addition, aerobic exercise plays a vital role in post-stroke rehabilitation by improving patients’ physical health and cognitive outcomes [ 5 ] , while a study by Zuo L revealed that among elderly individuals with carotid AS, populations classified as undertaking high-intensity exercise are more likely to gain high-risk carotid plaques, meaning those with preexisting high-risk carotid plaques may lose the benefits of physical activity [ 6 ] . Regarding diet, a reduced intake of sodium, sugar-sweetened beverages, alcohol, red meat, and processed meats can lower cardiovascular disease risks [ 7 ] . In addition, post-stroke depression (PSD), which is one of the most common and severe complications following a stroke, affects 25%–79% of stroke patients. After the development of PSD in stroke patients, patient disability and mortality rates can reach 70%–90%. Meanwhile, alleviating patients’ depressive symptoms can reduce the cardiovascular disease risks associated with sleep disorders [ 8 ] , while concurrent depression and sleep issues are linked to an elevated risk of cardiovascular events [ 9 ] . However, there has been limited attention given to the lifestyle and status of atherosclerosis patients in current research on carotid plaques. As such, this study explored the relationship between the various types of carotid plaque calcification and recurrent ischemic stroke through the calcification features which are easily observed in a computed tomography (CT) scan, by combining the 6-type plaque calcification classification with patients' physical activity, appetite, sleep and mood. Together, this provides supplementary imaging evidence for the early treatment and prognosis of stroke patients. Data and methods 1. Research type This study was designed as a single-center retrospective study. 2. Research subjects 2.1 Study population This study included patients who underwent head and neck CT angiography (CTA) and cranial magnetic resonance imaging (MRI) examinations at Lianyungang First People's Hospital from September 2022 to August 2023, with a 2–3-year clinical follow-up period. 2.2 Inclusion criteria Patients with recent onset of symptoms (< 3 months) including ischemic mild stroke, transient ischemic attack (TIA), and amaurosis fugax; Patients with carotid plaque confirmed by CTA (stenosis < 70%), according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. 2.3 Exclusion criteria Patients with incomplete imaging or clinical data; Patients who did not take their medicine as prescribed; Patients with non-intracranial atherosclerotic disease, including aneurysm, vasculitis, moyamoya disease, intracranial arterial dissection, reversible cerebral vasoconstriction syndrome (RCVS) and vertebrobasilar dolichoectasia (VBD) syndrome; Patients with suspected cardiac thrombus indicated by cardiac Doppler ultrasound or cardiac CTA; Patients with diagnosed coagulation disorders; Patients with heart failure or respiratory failure; Patients with renal impairment (serum creatinine > 133 µmol/L); Patients with severe consciousness disorders; Patients with intracranial hemorrhage, history of craniocerebral surgery, history of carotid stenting or carotid endarterectomy; Patients with previous stroke (diameter > 1.5 cm) and stroke in the posterior circulation area based on MRI. Inspection protocol The Somatom Definition Flash dual-source CT scanner (Siemens) was utilized. The scanning parameters were set as follows: current of 125 mA, voltage of 100 kV, collimation of 16×0.6 mm, and slice thickness of 0.75 mm. Additionally, a venous catheter, a double-bar release syringe, and ioxadilol contrast agent (320 mg I/mL, Jiangsu Hengrui Pharmaceuticals Co., Ltd., China) were used. For contrast enhancement, an 18-G cannula was selected for antecubital vein puncture, and non-ionic iodinated ioxadilol contrast agent (320 mg I/mL) was injected at a rate of 3 mL/s to 5 mL/s; the total dose and the flow rate of the contrast agent were individually quantified based on the patient's weight and the scanning range of the instrument. After completion of contrast agent injection, an additional 30 mL of normal saline was injected at the same flow rate. All patients included for carotid CTA had no history of heart failure or contraindications to iodinated contrast agents. First, the patients were placed in the supine position, and the CT scan range was from the aortic arch to the carotid sinus segment and from the feet to the head. Images were reviewed before and after contrast agent administration. The scanning range extended from the inferior margin of the aortic arch to the skull apex, with a duration of 8–12 seconds. The contrast agent tracer method was applied to monitor the CT value of the region of interest at either the aortic arch or carotid artery level. When the CT value exceeded 100 Hu, the system automatically triggered the scan after a 4-second delay, at which point the patient was instructed to hold their breath for another 4 seconds before scanning. Patients were instructed to avoid swallowing and moving their head or body, so that the collected data could be processed using 3D reconstruction technology, to obtain the required vascular images. All imaging examinations were performed by experienced radiologists. 4. Image analysis Two radiologists with > 5 years of experience in head and neck imaging diagnosis were assigned to select the enhanced phase of CTA scans for image analysis on the GPACS system. The region of calcified plaque was selected at the bifurcation of the common carotid artery, and comprehensive plaque evaluation was carried out. The morphological characteristics of the carotid plaque calcification were visually observed to determine the type and grouping of the plaque. If the plaques were present on bilateral carotid arteries, the larger plaque was analyzed. Neither of the two radiologists had access to the patient's clinical data. In case of discrepancies, the final decision was made by a third senior physician in the field. In this study, carotid calcified plaques were classified into six types, based on the aforementioned classification system.The various calcification types on CTA images are depicted in Fig. 1 . A, Type 1: Complete absence of calcification within the plaque. B, Type 2: Intimal or superficial calcification with thickness 2 mm. D, Type 4: Adventitial calcifications of < 2 mm thickness with internal soft plaque of < 2 mm thickness; negative rim sign. E, Type 5: Mixed pattern with intimal and bulky calcifications. F, Type 6: Positive rim sign; adventitial calcifications of 2 mm thickness. Stars indicate lumen, while arrows indicate plaque. 5. Data collection Clinical endpoints In this study, the clinical endpoints were defined as recurrent ischemic cerebrovascular events (ischemic mild stroke, TIA, and amaurosis fugax) occurring during follow-up (up to 3 years) or new ischemic foci observed by MRI. Endpoint data were collected through clinical interviews conducted by four neurologists with > 5 years of experience, and who were unaware of the CTA results. Ischemic mild stroke was defined as a focal cerebral dysfunction caused by vascular factors lasting > 24 hours, or a non-disabling stroke with a Modified Rankin Scale score of ≤ 3. TIA was defined as a temporary focal cerebral dysfunction caused by vascular factors lasting ≤ 24 hours, and without resulting in permanent neurological deficits. Amaurosis fugax, which is also known as transient monocular blindness, was defined as temporary vision loss caused by transient retinal ischemia in the carotid artery supply area. Living conditions Patients’ status of physical activity, appetite, sleep, and mood was assessed by telephone interview, and the interviewers were trained in standardized procedures. Physical activity, which primarily encompasses each patient’s primary forms of activity during the past month, is divided into high-level (e.g., jogging, tennis, vigorous gardening), moderate-level (e.g., brisk walking, stationary cycling, moderate gardening) and low-level (e.g., slow walking) activity, according to the International Physical Activity Questionnaire (IPAQ) [ 10 – 11 ] . Appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ), and divided into five grades: excellent, good, fair, poor, and very poor [ 12 – 13 ] . Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) to evaluate the patient's sleep quality over the past month, which was divided into four grades: excellent, good, poor, and very poor. Each patient’s mood was assessed using the Post-Stroke Depression Scale (PSDS), which inquired whether patients experienced low mood, depression, or despair after the stroke. The responses were categorized into four grades: none at all, a few days, more than half the days, and almost every day. Other relevant data Other measurements of relevance, taken in the morning within 48 hours of hospital admission, included fasting measurement of blood pressure, blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), lipoprotein A (LA), and homocysteine. Additionally, the patient's smoking and alcohol consumption habits, height, weight were recorded, and BMI was calculated. 6. Statistical methods SPSS 26.0 was utilized for data analysis. Continuous variables with normal distribution were expressed as mean ± standard deviation, and analysis of variance (ANOVA) was employed for intergroup comparisons. Data with skewed distributions were expressed as M (P25, P75) and a Mann-Whitney U test was employed for intergroup comparisons. Categorical variables were expressed as frequency and percentage, and a chi-square test was applied to determine statistically significant differences among groups. Simultaneously, the Kappa consistency test was applied to assess the consistency between or within observers. A p-value < 0.05 was considered statistically significant. Spearman’s correlation analysis was conducted to explore the correlation between plaque calcification types and recurrent ischemic stroke. Finally, a Cox proportional hazards model was utilized to investigate the association between plaque calcification types and recurrent ischemic stroke, giving hazard ratios (HR) and the corresponding 95% confidence intervals (CIs). Results 1. Baseline data of patients with carotid plaque calcification After screening according to predefined inclusion and exclusion criteria, 346 patients with carotid plaques were enrolled, with an average age of 65.58 ± 10.51 years, and 205 males (59.25%) and 141 females (40.75%). No statistically significant differences were observed in the clinical baseline characteristics data between the recurrent ischemic stroke group and the non-recurrent ischemic stroke group. The demographic and clinical data of the study population are presented in Table 1 . Table 1 Comparison of clinical baseline characteristics between the recurrent ischemic stroke group and the non-recurrent ischemic stroke group (n = 346) the recurrent stroke group(n = 158) the non-recurrent stroke group(n = 188) Statistic P Value Age(years) 67(60,73) 66(58,73) -0.846 0.397 Gender/Male(n, %) 92,58.22% 113,60.10% 0.125 0.743 BMI, kg/m 2 24.47(22.03,27.34) 24.76(22.86,26.66) -0.195 0.845 Smoking(n, %) 59,37.34% 59,31.38% 1.063 0.307 Drinking(n, %) 46,29.11% 56,29.78% 0.068 0.813 SBP,mmHg 149(135,159) 142(132,156) -1.347 0.178 DBP,mmHg 82(77,95) 81(78,92) -0.808 0.419 BS,mmol/L 5.11(4.63,6.78) 5.07(4.39,6.19) -1.354 0.176 TG,mmol/L 1.27(0.98,1.89) 1.36(0.94,1.82) -0.320 0.749 TC,mmol/L 4.47(3.57,5.11) 4.61(3.81,5.41) -1.333 0.183 LDL,mmol/L 2.8(2.17,3.24) 2.92(2.36,3.46) -1.492 0.136 HDL,mmol/L 1.11(0.94,1.29) 1.07(0.9,1.31) -0.559 0.576 LA,mg/L 168.6(89.25,339.35) 186.95(80.5,340.8) -0.296 0.767 homocysteine,umol/L 13.9(10.95,17.9) 13.9(11.4,17.67) -0.170 0.865 P values < 0.05 were considered statistically significant. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; BS, blood sugar; TG, triglycerides; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LA, lipoprotein A. Correlation analysis of carotid plaque calcification with recurrent ischemic stroke In the cohort of 346 patients with carotid plaques, the following recurrence rates were observed: Group 1 had 32 recurrent ischemic strokes (32/99, 32.32%); Group 2 had 27 (27/61, 44.26%); Group 3 had 16 (16/40, 40%); Group 4 had 23 (23/46, 50%); Group 5 had 2 (24/44, 54.54%)4; and Group 6 had 36 (36/56, 64.28%), as reported in Fig. 2 . We also analyzed the Spearman’s correlation between the type of carotid plaque calcification and recurrent ischemic stroke. The results showed that there was a weak positive correlation between the different types of plaque calcification and recurrent ischemic stroke (r = 0.215, p < 0.001). Construction of Cox proportional hazards model A Cox proportional hazards regression analysis was performed to evaluate the relationship of recurrent stroke with factors including sleep, appetite, physical activity, mood, and plaque calcification types, as shown in Table 2 . Plaque calcification types were significantly associated with the clinical endpoint (HR: 1.149,95%, CI: 1.059–1.247, p < 0.001). After adjusting for sleep, appetite, physical activity, and mood, the association between plaque calcification types and the clinical endpoint were statistically significant (HR: 1.128,95%, CI: 1.037–1.226, p = 0.005). The probability of recurrence-free survival for patients with different plaque calcification types is illustrated in Fig. 3 . Table 2 Cox proportional hazards regression model for clinical endpoints Categories Univariate analysis Multivariate analysis HR(95% CI) P-value HR(95% CI) P- value Plaque classification 1.149 (1.059–1.247) < 0.001 1.128 (1.037–1.226) 0.005 Appetite 1.350 (1.172–1.554) < 0.001 1.311 (1.136–1.512) < 0.001 Physical activity 1 Ref. 2 0.738 (0.443–1.230) 0.244 3 0.983 (0.431–2.241) 0.968 Mood 0 Ref. 1 2.304 (1.169–4.542) 0.016 2 Ref. 3 0.747 (0.104–5.366) 0.772 Sleep 1.079 (0.894–1.303) 0.428 Discussion In this study, we focused on calcification, which is more commonly observed in clinical practice, instead of high-risk and low-risk plaques. Through CTA technology and a novel classification system for carotid plaque calcification, we categorized common carotid calcified plaques and analyzed their correlation with recurrent ischemic stroke by integrating sleep, appetite, physical activity, and mood. The findings of these analyses demonstrated that plaque calcification types were correlated with stroke recurrence, which will help patients to develop better risk awareness and management strategies for carotid plaques after their initial diagnosis of cerebral arterial thrombosis. This will support patients in being more proactive in collaboration in clinical diagnosis and treatment. In this study, the images were read by two radiologists with > 5 years of experience in head and neck imaging diagnosis. During imaging, Type 2 calcifications were readily identifiable, whereas Type 3 and Type 5 calcifications were occasionally difficult to distinguish. The Kappa consistency analysis revealed high consistency among observers (κ = 0.9). First, we focused on observing the morphology of calcified plaques at the carotid bifurcation and classified the plaque calcification types to analyze their relationship with recurrent stroke. A total of 6 plaque types were identified and plaques with positive rim signs were associated with the highest risk of recurrent stroke, with 36/56 patients experiencing recurrent strokes. This result was further confirmed by Spearman’s correlation analysis, which demonstrated statistically significant correlation between plaque calcification types and recurrent stroke. This result was further confirmed by Spearman’s correlation analysis, which demonstrated a statistically significant weak positive correlation between plaque calcification types and recurrent stroke. Moreover, according to Cox proportional hazards model analysis, there was a significant link between plaque calcification types and clinical outcomes, with a hazard ratio of 1.128. L. B. Eisenmenger, et al., reported similar findings showing that a positive rim sign was a strong predictor of carotid plaque hemorrhage [ 14 ] . However, the underlying mechanism remained unclear. This finding was potentially due to increased neovascular proliferation and inflammation, resulting in decreased plaque stability which led to plaque rupture and ischemic cerebrovascular eventss, but this hypothesis requires further experimental verification. Previous studies have shown that patients with Type 6 plaques had the highest incidence of ipsilateral acute ischemic stroke, with 35/71 patients developing ipsilateral anterior circulation acute ischemic stroke. In addition, Saba L, et al.[4] also found that Type 6 plaques were most strongly correlated with stroke, transient ischemic attacks, and ipsilateral infarction. Meanwhile, different plaque calcification types appeared to play distinct roles, with the odds ratios of calcification types showing an increasing trend, which aligned with our findings. In this study, a comparison between Type 4 and Type 6 plaques revealed statistically significant differences in the incidence of recurrent stroke. Both types exhibited identical calcification morphology, although the thickness of soft plaques was found to be distinct. Meanwhile, a retrospective study demonstrated that every 1 mm increase in the size of a plaque raised the risk of stroke or transient ischemic attack 2.7-fold [ 15 ] , which was similar to the findings of this study. Furthermore, Nandalur KR et al. found that the proportion of carotid plaque calcification, rather than absolute volume, correlated with plaque stability. Specifically, for certain patients, calcified carotid plaques accounting for > 45% of total plaque volume may indicate better stability [ 16 ] . Our analysis showed that Type 3 calcified plaques were linked with a lower recurrence risk compared to Type 2, although the difference was not statistically significant. In contrast, Type 1, which is characterized by non-calcified carotid plaques, exhibited the lowest recurrence risk. This could be attributed to the complex mechanisms of plaque in recurrent stroke, which was involved in various metabolic processes that often conflict and overlap, and so this warrants further investigation. Type 5 calcified plaques, representing a mixed type of plaque with intimal and bulky calcification, also require further research. Secondly, the Cox proportional hazards model analysis found a significant association between appetite and recurrent stroke after adjusting for sleep, physical activity, mood, and plaque types (HR: 1.311, 95% CI: 1.136–1.512, p < 0.001). This may be attributed to an inadequate intake of essential nutrients such as high-quality protein and essential fatty acids due to poor appetite, which disrupts lipoprotein synthesis and transport, ultimately leading to abnormal lipid metabolism and the occurrence of cerebrovascular events.However, the causal relationship between appetite and recurrent stroke has not been confirmed, and other confounding factors may be involved, requiring further exploration. Our study has some limitations. First, This study is a single-center retrospective study with a limited sample size, and there may be selection bias. Second,we excluded patients with severe stenosis, making the study’s findings applicable only to those with mild to moderate carotid stenosis, and so severe stenosis requires further exploration in future research.Third, the diagnostic reliability of TIA and amaurosis fugax is generally lower than that of stroke. However, we have minimized diagnostic errors through independent expert evaluations. Finally, we cannot completely rule out cardiac embolism or intracranial atherosclerotic plaques as potential stroke causes. However, during patient inclusion/exclusion, experienced neurologists verified the clinical events independently, thereby reducing the likelihood of statistical inclusion of recurrent strokes caused by non-cranial carotid artery regions. The calcified plaque classification model used in this study requires further validation through multi-center, large-sample prospective longitudinal cohort studies to confirm its clinical applicability and generalizability. At present, our study has some clinical significance, even though we cannot yet definitively prove a causal relationship between plaque calcification and recurrent stroke, nor can we confirm that calcification is merely an accompanying phenomenon of AS. Nevertheless, the findings of this study demonstrate a correlative relationship between plaque calcification morphology and recurrent stroke occurrence. CONCLUSION This study highlighted a correlation between carotid plaque calcification types and the recurrence of stroke. These findings provide a new approach to studying carotid atherosclerotic plaque calcification and further imaging-based evidence for the risk assessment of recurrent ischemic stroke. Declarations ETHICS APPROVAL AND CONSENT TO PARTICIPATE This study was reviewed and approved by the Medical Ethics Committee of Lianyungang First People's Hospital (KY-20220726002-01) and conducted in accordance with the Declaration of Helsinki (version 2013, Fortaleza, Brazil). The requirement for written informed consent was waived by the above-mentioned IRB due to the retrospective nature of the study and the anonymization of patient data, which posed no additional risks to the participants. All procedures were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This work has been supported by the Lianyungang City health Commission surface of State project foundation (Grant No.202204). Author Contribution T. C.:Conceptualization,Writing-Original Draft. Y. Z.:Conceptualization. Y.G.:Formal analysis.Y. L.:Methodology.Y. Z.:Data curation.Y. G.:Writing-Review&Editing,Supervision. All authors read and approved the final manuscript. Acknowledgement Thanks to all the staff of the Department of Radiology of The First People's Hospital of Lianyungang for their help and support. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Chen Y, Wright N, Guo Y, Turnbull I, Kartsonaki C, Yang L, et al. 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Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA. AJNR Am J Neuroradiol. 2016;37(8):1496–503. Gupta A, Baradaran H, Kamel H, Pandya A, Mangla A, Dunning A, et al. Evaluation of computed tomography angiography plaque thickness measurements in high-grade carotid artery stenosis. Stroke. 2014;45(3):740–5. Nandalur KR, Hardie AD, Raghavan P, Schipper MJ, Baskurt E, Kramer CM. Composition of the stable carotid plaque: insights from a multidetector computed tomography study of plaque volume. Stroke. 2007;38(3):935–40. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Mar, 2026 Read the published version in BMC Medical Imaging → Version 1 posted Editorial decision: Revision requested 23 Feb, 2026 Reviews received at journal 22 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviewers agreed at journal 06 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviews received at journal 27 Jan, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviewers invited by journal 27 Jan, 2026 Editor assigned by journal 27 Jan, 2026 Editor invited by journal 19 Jan, 2026 Submission checks completed at journal 17 Jan, 2026 First submitted to journal 17 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8507625","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":581423402,"identity":"2d047bf6-9444-46a3-a249-274e22617e2c","order_by":0,"name":"Tianyu Chu","email":"","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tianyu","middleName":"","lastName":"Chu","suffix":""},{"id":581423403,"identity":"c5fe7b72-5a14-40e4-b8ee-15f42dd3bded","order_by":1,"name":"Yonggang Zhang","email":"","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yonggang","middleName":"","lastName":"Zhang","suffix":""},{"id":581423405,"identity":"60dc3dcf-c8d1-48f9-b088-0e19bacaafc8","order_by":2,"name":"Yingqi Gao","email":"","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yingqi","middleName":"","lastName":"Gao","suffix":""},{"id":581423407,"identity":"fb773f0c-82cd-486e-869b-aab7362b7a3c","order_by":3,"name":"Yin Liu","email":"","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yin","middleName":"","lastName":"Liu","suffix":""},{"id":581423408,"identity":"0d06f04a-01d9-4007-9c2f-d1ed6056b5a1","order_by":4,"name":"Yinan Zhao","email":"","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yinan","middleName":"","lastName":"Zhao","suffix":""},{"id":581423409,"identity":"d8c4a514-1385-45ed-8d7e-84e4a81ba586","order_by":5,"name":"Yan Gu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYNCCCgk5NvYGBgMw5wBRWs7YGPPzHCBFC2NbWuLMGQlQHiEt8hE5hp8L2A4zbrj59kDRzTYGOb4bCYyfC/BoMbyRYyw9g+cws8HtvATj3DYGY8kbCczSM/BpmZFjIM0jcZjN4HaOAUhL4oYbCWzMPPi1GP/mMTjMY3DzDFhLPUEt8hI5ZtI8CWkSkjN4wFoSDAhpMeB5VmbNc8DGgJ8H6LCccxKGM888bJbGa0t78ubbvP8k6tvYz5gZ55TZyPMdTz74Ga8tBzgMYGw2IEsCSDM24NEAtKWB/QGMzfwAl6pRMApGwSgY2QAAClFJuoz5KgkAAAAASUVORK5CYII=","orcid":"","institution":"Lianyungang Clinical College of Nanjing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Gu","suffix":""}],"badges":[],"createdAt":"2026-01-03 14:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8507625/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8507625/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12880-026-02293-4","type":"published","date":"2026-03-26T16:12:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101439940,"identity":"38b47b46-8f85-4dd3-bdab-ec51d6e95439","added_by":"auto","created_at":"2026-01-29 16:51:04","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50232,"visible":true,"origin":"","legend":"\u003cp\u003e6 types of calcifications on CTA images.\u003c/p\u003e","description":"","filename":"Figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8507625/v1/54492efd787e1d25bd88a3c8.jpeg"},{"id":101439938,"identity":"aa20d3ab-29db-4b3e-8b81-ad0512eb810b","added_by":"auto","created_at":"2026-01-29 16:51:04","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":288989,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence of recurrent ischemic stroke in Type 1 to Type 6 carotid plaques.\u003c/p\u003e","description":"","filename":"Figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8507625/v1/504b3894271a9be22396457b.jpeg"},{"id":101439939,"identity":"7e19a856-2afd-411f-9bf5-efa34e043dc8","added_by":"auto","created_at":"2026-01-29 16:51:04","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":72881,"visible":true,"origin":"","legend":"\u003cp\u003eRecurrence-free survival curves of ischemic stroke in patients with Type 1 to Type 6 carotid plaque calcification.\u003c/p\u003e","description":"","filename":"Figure3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8507625/v1/ed368c7c3ee015369e3a2f3c.jpeg"},{"id":105755753,"identity":"e0b615be-689a-4564-b63a-4fd08fc0a021","added_by":"auto","created_at":"2026-03-30 16:30:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1074776,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8507625/v1/1ff55346-2ba3-4507-8fa0-199679db6d19.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Study on the correlation between carotid plaque calcification types and the recurrence of ischemic stroke","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStroke is the leading cause of death and disability worldwide, and stroke recurrence is associated with a heightened risk of recurrence or death within five years after the first stroke \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In addition, recurrent ischemic strokes often cause more severe cerebrovascular damage and cognitive impairment than the first stroke. Patients with carotid atherosclerosis (AS) plaques have a significantly increased risk of recurrent cerebrovascular events, and they are a major contributor to ischemic stroke \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The primary underlying cause of ischemic stroke in these patients is the rupture of vulnerable carotid plaques, which may trigger thrombosis and embolism, ultimately blocking downstream vessels. In addition, calcification is commonly observed in atherosclerotic plaques, and it typically develops during the progression of atherosclerotic lesions, although its exact mechanisms remain unclear. Apoptotic cells, extracellular matrix, and necrotic core material can serve as precursors for microscopic calcium deposits, which may further coalesce into larger calcified plaques\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. However, the current research on calcified plaques remains controversial, as the impact of calcification with different sizes and morphologies on cerebrovascular events shows variable results. Moreover, existing studies predominantly focus on a single calcification feature rather than comprehensive analysis. In contrast, this study comprehensively investigated the size, location, and shape characteristics of plaque calcification, following the 6-type classification proposed by Saba L\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, as follows: Type 1: complete absence of calcification within the plaque; Type 2: intimal or superficial calcifications; Type 3: deep or bulky calcifications; Type 4: adventitial calcifications with internal soft plaque of \u0026lt; 2 mm thickness (negative rim sign); Type 5: mixed patterns with intimal and bulky calcifications; and Type 6: positive rim sign.\u003c/p\u003e \u003cp\u003eFor stroke patients, it is critical to equally monitor their physical activity, appetite, sleep, and mood following stroke onset. In addition, aerobic exercise plays a vital role in post-stroke rehabilitation by improving patients’ physical health and cognitive outcomes\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, while a study by Zuo L revealed that among elderly individuals with carotid AS, populations classified as undertaking high-intensity exercise are more likely to gain high-risk carotid plaques, meaning those with preexisting high-risk carotid plaques may lose the benefits of physical activity \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Regarding diet, a reduced intake of sodium, sugar-sweetened beverages, alcohol, red meat, and processed meats can lower cardiovascular disease risks\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. In addition, post-stroke depression (PSD), which is one of the most common and severe complications following a stroke, affects 25%–79% of stroke patients. After the development of PSD in stroke patients, patient disability and mortality rates can reach 70%–90%. Meanwhile, alleviating patients’ depressive symptoms can reduce the cardiovascular disease risks associated with sleep disorders\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, while concurrent depression and sleep issues are linked to an elevated risk of cardiovascular events\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, there has been limited attention given to the lifestyle and status of atherosclerosis patients in current research on carotid plaques.\u003c/p\u003e \u003cp\u003eAs such, this study explored the relationship between the various types of carotid plaque calcification and recurrent ischemic stroke through the calcification features which are easily observed in a computed tomography (CT) scan, by combining the 6-type plaque calcification classification with patients' physical activity, appetite, sleep and mood. Together, this provides supplementary imaging evidence for the early treatment and prognosis of stroke patients.\u003c/p\u003e "},{"header":"Data and methods","content":"\u003ch3\u003e1. Research type\u003c/h3\u003e\u003cp\u003eThis study was designed as a single-center retrospective study.\u003c/p\u003e\u003ch3\u003e2. Research subjects\u003c/h3\u003e\u003ch2\u003e2.1 Study population\u003c/h2\u003e\u003cp\u003eThis study included patients who underwent head and neck CT angiography (CTA) and cranial magnetic resonance imaging (MRI) examinations at Lianyungang First People's Hospital from September 2022 to August 2023, with a 2–3-year clinical follow-up period.\u003c/p\u003e\u003ch2\u003e2.2 Inclusion criteria\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003ePatients with recent onset of symptoms (\u0026lt; 3 months) including ischemic mild stroke, transient ischemic attack (TIA), and amaurosis fugax;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with carotid plaque confirmed by CTA (stenosis \u0026lt; 70%), according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003ch2\u003e2.3 Exclusion criteria\u003c/h2\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003ePatients with incomplete imaging or clinical data;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients who did not take their medicine as prescribed;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with non-intracranial atherosclerotic disease, including aneurysm, vasculitis, moyamoya disease, intracranial arterial dissection, reversible cerebral vasoconstriction syndrome (RCVS) and vertebrobasilar dolichoectasia (VBD) syndrome;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with suspected cardiac thrombus indicated by cardiac Doppler ultrasound or cardiac CTA;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with diagnosed coagulation disorders;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with heart failure or respiratory failure;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with renal impairment (serum creatinine \u0026gt; 133 µmol/L);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with severe consciousness disorders;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with intracranial hemorrhage, history of craniocerebral surgery, history of carotid stenting or carotid endarterectomy;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatients with previous stroke (diameter \u0026gt; 1.5 cm) and stroke in the posterior circulation area based on MRI.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eInspection protocol\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003eThe Somatom Definition Flash dual-source CT scanner (Siemens) was utilized. The scanning parameters were set as follows: current of 125 mA, voltage of 100 kV, collimation of 16×0.6 mm, and slice thickness of 0.75 mm. Additionally, a venous catheter, a double-bar release syringe, and ioxadilol contrast agent (320 mg I/mL, Jiangsu Hengrui Pharmaceuticals Co., Ltd., China) were used. For contrast enhancement, an 18-G cannula was selected for antecubital vein puncture, and non-ionic iodinated ioxadilol contrast agent (320 mg I/mL) was injected at a rate of 3 mL/s to 5 mL/s; the total dose and the flow rate of the contrast agent were individually quantified based on the patient's weight and the scanning range of the instrument. After completion of contrast agent injection, an additional 30 mL of normal saline was injected at the same flow rate.\u003c/p\u003e\u003cp\u003eAll patients included for carotid CTA had no history of heart failure or contraindications to iodinated contrast agents. First, the patients were placed in the supine position, and the CT scan range was from the aortic arch to the carotid sinus segment and from the feet to the head. Images were reviewed before and after contrast agent administration. The scanning range extended from the inferior margin of the aortic arch to the skull apex, with a duration of 8–12 seconds. The contrast agent tracer method was applied to monitor the CT value of the region of interest at either the aortic arch or carotid artery level. When the CT value exceeded 100 Hu, the system automatically triggered the scan after a 4-second delay, at which point the patient was instructed to hold their breath for another 4 seconds before scanning. Patients were instructed to avoid swallowing and moving their head or body, so that the collected data could be processed using 3D reconstruction technology, to obtain the required vascular images. All imaging examinations were performed by experienced radiologists.\u003c/p\u003e\u003ch3\u003e4. Image analysis\u003c/h3\u003e\u003cp\u003eTwo radiologists with \u0026gt; 5 years of experience in head and neck imaging diagnosis were assigned to select the enhanced phase of CTA scans for image analysis on the GPACS system. The region of calcified plaque was selected at the bifurcation of the common carotid artery, and comprehensive plaque evaluation was carried out. The morphological characteristics of the carotid plaque calcification were visually observed to determine the type and grouping of the plaque. If the plaques were present on bilateral carotid arteries, the larger plaque was analyzed. Neither of the two radiologists had access to the patient's clinical data. In case of discrepancies, the final decision was made by a third senior physician in the field.\u003c/p\u003e\u003cp\u003eIn this study, carotid calcified plaques were classified into six types, based on the aforementioned classification system.The various calcification types on CTA images are depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eA, Type 1: Complete absence of calcification within the plaque. B, Type 2: Intimal or superficial calcification with thickness \u0026lt; 2 mm. C, Type 3: Deep or bulky calcification with thickness \u0026gt; 2 mm. D, Type 4: Adventitial calcifications of \u0026lt; 2 mm thickness with internal soft plaque of \u0026lt; 2 mm thickness; negative rim sign. E, Type 5: Mixed pattern with intimal and bulky calcifications. F, Type 6: Positive rim sign; adventitial calcifications of \u0026lt; 2-mm-thickness with internal soft plaque of \u0026gt; 2 mm thickness. Stars indicate lumen, while arrows indicate plaque.\u003c/p\u003e\u003ch3\u003e5. Data collection\u003c/h3\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eClinical endpoints\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003eIn this study, the clinical endpoints were defined as recurrent ischemic cerebrovascular events (ischemic mild stroke, TIA, and amaurosis fugax) occurring during follow-up (up to 3 years) or new ischemic foci observed by MRI. Endpoint data were collected through clinical interviews conducted by four neurologists with \u0026gt; 5 years of experience, and who were unaware of the CTA results. Ischemic mild stroke was defined as a focal cerebral dysfunction caused by vascular factors lasting \u0026gt; 24 hours, or a non-disabling stroke with a Modified Rankin Scale score of ≤ 3. TIA was defined as a temporary focal cerebral dysfunction caused by vascular factors lasting ≤ 24 hours, and without resulting in permanent neurological deficits. Amaurosis fugax, which is also known as transient monocular blindness, was defined as temporary vision loss caused by transient retinal ischemia in the carotid artery supply area.\u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eLiving conditions\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003ePatients’ status of physical activity, appetite, sleep, and mood was assessed by telephone interview, and the interviewers were trained in standardized procedures.\u003c/p\u003e\u003cp\u003ePhysical activity, which primarily encompasses each patient’s primary forms of activity during the past month, is divided into high-level (e.g., jogging, tennis, vigorous gardening), moderate-level (e.g., brisk walking, stationary cycling, moderate gardening) and low-level (e.g., slow walking) activity, according to the International Physical Activity Questionnaire (IPAQ) \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAppetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ), and divided into five grades: excellent, good, fair, poor, and very poor \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) to evaluate the patient's sleep quality over the past month, which was divided into four grades: excellent, good, poor, and very poor.\u003c/p\u003e\u003cp\u003eEach patient’s mood was assessed using the Post-Stroke Depression Scale (PSDS), which inquired whether patients experienced low mood, depression, or despair after the stroke. The responses were categorized into four grades: none at all, a few days, more than half the days, and almost every day.\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eOther relevant data\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003eOther measurements of relevance, taken in the morning within 48 hours of hospital admission, included fasting measurement of blood pressure, blood glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), lipoprotein A (LA), and homocysteine. Additionally, the patient's smoking and alcohol consumption habits, height, weight were recorded, and BMI was calculated.\u003c/p\u003e\u003ch3\u003e6. Statistical methods\u003c/h3\u003e\u003cp\u003eSPSS 26.0 was utilized for data analysis. Continuous variables with normal distribution were expressed as mean ± standard deviation, and analysis of variance (ANOVA) was employed for intergroup comparisons. Data with skewed distributions were expressed as M (P25, P75) and a Mann-Whitney U test was employed for intergroup comparisons. Categorical variables were expressed as frequency and percentage, and a chi-square test was applied to determine statistically significant differences among groups. Simultaneously, the Kappa consistency test was applied to assess the consistency between or within observers. A p-value \u0026lt; 0.05 was considered statistically significant. Spearman’s correlation analysis was conducted to explore the correlation between plaque calcification types and recurrent ischemic stroke. Finally, a Cox proportional hazards model was utilized to investigate the association between plaque calcification types and recurrent ischemic stroke, giving hazard ratios (HR) and the corresponding 95% confidence intervals (CIs).\u003c/p\u003e"},{"header":"Results","content":"\n\u003ch3\u003e1. Baseline data of patients with carotid plaque calcification\u003c/h3\u003e\n\u003cp\u003eAfter screening according to predefined inclusion and exclusion criteria, 346 patients with carotid plaques were enrolled, with an average age of 65.58\u0026thinsp;\u0026plusmn;\u0026thinsp;10.51 years, and 205 males (59.25%) and 141 females (40.75%). No statistically significant differences were observed in the clinical baseline characteristics data between the recurrent ischemic stroke group and the non-recurrent ischemic stroke group. The demographic and clinical data of the study population are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical baseline characteristics between the recurrent ischemic stroke group and the non-recurrent ischemic stroke group (n\u0026thinsp;=\u0026thinsp;346)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ethe recurrent stroke group(n\u0026thinsp;=\u0026thinsp;158)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ethe non-recurrent stroke group(n\u0026thinsp;=\u0026thinsp;188)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStatistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(60,73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66(58,73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender/Male(n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92,58.22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113,60.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.47(22.03,27.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.76(22.86,26.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.845\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking(n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59,37.34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59,31.38%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinking(n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46,29.11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56,29.78%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP,mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e149(135,159)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142(132,156)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP,mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82(77,95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81(78,92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.808\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBS,mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.11(4.63,6.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.07(4.39,6.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG,mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.27(0.98,1.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.36(0.94,1.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTC,mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.47(3.57,5.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.61(3.81,5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL,mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8(2.17,3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.92(2.36,3.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL,mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.11(0.94,1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.07(0.9,1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.559\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLA,mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168.6(89.25,339.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186.95(80.5,340.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehomocysteine,umol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.9(10.95,17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9(11.4,17.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.865\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eP values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003cp\u003eSBP, Systolic blood pressure; DBP, Diastolic blood pressure; BS, blood sugar; TG, triglycerides; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LA, lipoprotein A.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eCorrelation analysis of carotid plaque calcification with recurrent ischemic stroke\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eIn the cohort of 346 patients with carotid plaques, the following recurrence rates were observed: Group 1 had 32 recurrent ischemic strokes (32/99, 32.32%); Group 2 had 27 (27/61, 44.26%); Group 3 had 16 (16/40, 40%); Group 4 had 23 (23/46, 50%); Group 5 had 2 (24/44, 54.54%)4; and Group 6 had 36 (36/56, 64.28%), as reported in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe also analyzed the Spearman\u0026rsquo;s correlation between the type of carotid plaque calcification and recurrent ischemic stroke. The results showed that there was a weak positive correlation between the different types of plaque calcification and recurrent ischemic stroke (r\u0026thinsp;=\u0026thinsp;0.215, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eConstruction of Cox proportional hazards model\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eA Cox proportional hazards regression analysis was performed to evaluate the relationship of recurrent stroke with factors including sleep, appetite, physical activity, mood, and plaque calcification types, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Plaque calcification types were significantly associated with the clinical endpoint (HR: 1.149,95%, CI: 1.059\u0026ndash;1.247, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for sleep, appetite, physical activity, and mood, the association between plaque calcification types and the clinical endpoint were statistically significant (HR: 1.128,95%, CI: 1.037\u0026ndash;1.226, p\u0026thinsp;=\u0026thinsp;0.005). The probability of recurrence-free survival for patients with different plaque calcification types is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCox proportional hazards regression model for clinical endpoints\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCategories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP- value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlaque classification\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.149 (1.059\u0026ndash;1.247)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.128 (1.037\u0026ndash;1.226)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.350 (1.172\u0026ndash;1.554)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.311 (1.136\u0026ndash;1.512)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.738 (0.443\u0026ndash;1.230)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.983 (0.431\u0026ndash;2.241)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.304 (1.169\u0026ndash;4.542)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.747 (0.104\u0026ndash;5.366)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.079 (0.894\u0026ndash;1.303)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we focused on calcification, which is more commonly observed in clinical practice, instead of high-risk and low-risk plaques. Through CTA technology and a novel classification system for carotid plaque calcification, we categorized common carotid calcified plaques and analyzed their correlation with recurrent ischemic stroke by integrating sleep, appetite, physical activity, and mood. The findings of these analyses demonstrated that plaque calcification types were correlated with stroke recurrence, which will help patients to develop better risk awareness and management strategies for carotid plaques after their initial diagnosis of cerebral arterial thrombosis. This will support patients in being more proactive in collaboration in clinical diagnosis and treatment.\u003c/p\u003e \u003cp\u003eIn this study, the images were read by two radiologists with \u0026gt;\u0026thinsp;5 years of experience in head and neck imaging diagnosis. During imaging, Type 2 calcifications were readily identifiable, whereas Type 3 and Type 5 calcifications were occasionally difficult to distinguish. The Kappa consistency analysis revealed high consistency among observers (κ\u0026thinsp;=\u0026thinsp;0.9).\u003c/p\u003e \u003cp\u003eFirst, we focused on observing the morphology of calcified plaques at the carotid bifurcation and classified the plaque calcification types to analyze their relationship with recurrent stroke. A total of 6 plaque types were identified and plaques with positive rim signs were associated with the highest risk of recurrent stroke, with 36/56 patients experiencing recurrent strokes. This result was further confirmed by Spearman\u0026rsquo;s correlation analysis, which demonstrated statistically significant correlation between plaque calcification types and recurrent stroke. This result was further confirmed by Spearman\u0026rsquo;s correlation analysis, which demonstrated a statistically significant weak positive correlation between plaque calcification types and recurrent stroke. Moreover, according to Cox proportional hazards model analysis, there was a significant link between plaque calcification types and clinical outcomes, with a hazard ratio of 1.128. L. B. Eisenmenger, et al., reported similar findings showing that a positive rim sign was a strong predictor of carotid plaque hemorrhage\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. However, the underlying mechanism remained unclear. This finding was potentially due to increased neovascular proliferation and inflammation, resulting in decreased plaque stability which led to plaque rupture and ischemic cerebrovascular eventss, but this hypothesis requires further experimental verification. Previous studies have shown that patients with Type 6 plaques had the highest incidence of ipsilateral acute ischemic stroke, with 35/71 patients developing ipsilateral anterior circulation acute ischemic stroke. In addition, Saba L, et al.[4] also found that Type 6 plaques were most strongly correlated with stroke, transient ischemic attacks, and ipsilateral infarction. Meanwhile, different plaque calcification types appeared to play distinct roles, with the odds ratios of calcification types showing an increasing trend, which aligned with our findings.\u003c/p\u003e \u003cp\u003eIn this study, a comparison between Type 4 and Type 6 plaques revealed statistically significant differences in the incidence of recurrent stroke. Both types exhibited identical calcification morphology, although the thickness of soft plaques was found to be distinct. Meanwhile, a retrospective study demonstrated that every 1 mm increase in the size of a plaque raised the risk of stroke or transient ischemic attack 2.7-fold \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, which was similar to the findings of this study. Furthermore, Nandalur KR et al. found that the proportion of carotid plaque calcification, rather than absolute volume, correlated with plaque stability. Specifically, for certain patients, calcified carotid plaques accounting for \u0026gt;\u0026thinsp;45% of total plaque volume may indicate better stability \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Our analysis showed that Type 3 calcified plaques were linked with a lower recurrence risk compared to Type 2, although the difference was not statistically significant. In contrast, Type 1, which is characterized by non-calcified carotid plaques, exhibited the lowest recurrence risk. This could be attributed to the complex mechanisms of plaque in recurrent stroke, which was involved in various metabolic processes that often conflict and overlap, and so this warrants further investigation. Type 5 calcified plaques, representing a mixed type of plaque with intimal and bulky calcification, also require further research.\u003c/p\u003e \u003cp\u003eSecondly, the Cox proportional hazards model analysis found a significant association between appetite and recurrent stroke after adjusting for sleep, physical activity, mood, and plaque types (HR: 1.311, 95% CI: 1.136\u0026ndash;1.512, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This may be attributed to an inadequate intake of essential nutrients such as high-quality protein and essential fatty acids due to poor appetite, which disrupts lipoprotein synthesis and transport, ultimately leading to abnormal lipid metabolism and the occurrence of cerebrovascular events.However, the causal relationship between appetite and recurrent stroke has not been confirmed, and other confounding factors may be involved, requiring further exploration.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, This study is a single-center retrospective study with a limited sample size, and there may be selection bias. Second,we excluded patients with severe stenosis, making the study\u0026rsquo;s findings applicable only to those with mild to moderate carotid stenosis, and so severe stenosis requires further exploration in future research.Third, the diagnostic reliability of TIA and amaurosis fugax is generally lower than that of stroke. However, we have minimized diagnostic errors through independent expert evaluations. Finally, we cannot completely rule out cardiac embolism or intracranial atherosclerotic plaques as potential stroke causes. However, during patient inclusion/exclusion, experienced neurologists verified the clinical events independently, thereby reducing the likelihood of statistical inclusion of recurrent strokes caused by non-cranial carotid artery regions.\u003c/p\u003e \u003cp\u003eThe calcified plaque classification model used in this study requires further validation through multi-center, large-sample prospective longitudinal cohort studies to confirm its clinical applicability and generalizability. At present, our study has some clinical significance, even though we cannot yet definitively prove a causal relationship between plaque calcification and recurrent stroke, nor can we confirm that calcification is merely an accompanying phenomenon of AS. Nevertheless, the findings of this study demonstrate a correlative relationship between plaque calcification morphology and recurrent stroke occurrence.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study highlighted a correlation between carotid plaque calcification types and the recurrence of stroke. These findings provide a new approach to studying carotid atherosclerotic plaque calcification and further imaging-based evidence for the risk assessment of recurrent ischemic stroke.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE\u003c/h2\u003e \u003cp\u003e This study was reviewed and approved by the Medical Ethics Committee of Lianyungang First People's Hospital (KY-20220726002-01) and conducted in accordance with the Declaration of Helsinki (version 2013, Fortaleza, Brazil). The requirement for written informed consent was waived by the above-mentioned IRB due to the retrospective nature of the study and the anonymization of patient data, which posed no additional risks to the participants. All procedures were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work has been supported by the Lianyungang City health Commission surface of State project foundation (Grant No.202204).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eT. C.:Conceptualization,Writing-Original Draft. Y. Z.:Conceptualization. Y.G.:Formal analysis.Y. L.:Methodology.Y. Z.:Data curation.Y. G.:Writing-Review\u0026amp;Editing,Supervision. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThanks to all the staff of the Department of Radiology of The First People's Hospital of Lianyungang for their help and support.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChen Y, Wright N, Guo Y, Turnbull I, Kartsonaki C, Yang L, et al. Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0\u0026middot;5 million Chinese adults. Lancet Glob Health. 2020;8(4):e580\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao X, Li R, Hippe DS, Hatsukami TS, Yuan C. CARE-II Investigators. Chinese Atherosclerosis Risk Evaluation (CARE II) study: a novel cross-sectional, multicentre study of the prevalence of high-risk atherosclerotic carotid plaque in Chinese patients with ischaemic cerebrovascular events-design and rationale. Stroke Vasc Neurol. 2017;2(1):15\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114(12):1852\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaba L, Chen H, Cau R, Rubeis GD, Zhu G, Pisu F, et al. Impact Analysis of Different CT Configurations of Carotid Artery Plaque Calcifications on Cerebrovascular Events. AJNR Am J Neuroradiol. 2022;43(2):272\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu M, Chen W, Zhang J. Aerobic exercise, an effective intervention for cognitive impairment after ischemic stroke. Front Aging Neurosci. 2025;17:1514271.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZuo L, Kavousi M, Van Oortmerssen JAE, Voortman T, Ikram MK, Bos D. Physical activity relates to carotid plaque vulnerability in older persons with subclinical carotid atherosclerosis. EBioMedicine. 2025;119:105894.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZyriax BC, Windler E. Lifestyle changes to prevent cardio- and cerebrovascular disease at midlife: A systematic review. Maturitas. 2023;167:60\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou W, Sun L, Zeng L, Wan L. Mediation of the association between sleep disorders and cardiovascular disease by depressive symptoms: An analysis of the National health and Nutrition Examination Survey (NHANES) 2017\u0026ndash;2020. Prev Med Rep. 2023;33:102183.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu C, Wang J, Wang J, Zhong Q, Huang Y, Chen Y, et al. Associations between depressive symptoms and sleep duration for predicting cardiovascular disease onset: A prospective cohort study. J Affect Disord. 2022;303:1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZirnsak M, Meisinger C, Linseisen J, Ertl M, Zickler P, Naumann M, et al. Associations between pre-stroke physical activity and physical quality of life three months after stroke in patients with mild disability. PLoS ONE. 2022;17(6):e0266318.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu W, Liang W, Ye Z, Wu Y, He X, Xue R, et al. Association of physical activity and risk of atrial fibrillation in heart failure with preserved ejection fraction. Nutr Metab Cardiovasc Dis. 2021;31(1):247\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto M, Nozoe M, Ikeji R, Seike H, Yoshida Y, Shomoto K. Anorexia assessment using the Simplified Nutritional Appetite Questionnaire and its association with activities of daily living in patients with stroke. Nutrition. 2024;117:112238.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto M, Nozoe M, Ikeji R, Seike H, Yoshida Y, Shomoto K. Anorexia assessment using the Simplified Nutritional Appetite Questionnaire and its association with activities of daily living in patients with stroke. Nutrition. 2024;117:112238.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEisenmenger LB, Aldred BW, Kim SE, Stoddard GJ, de Havenon A, Treiman GS, et al. Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA. AJNR Am J Neuroradiol. 2016;37(8):1496\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupta A, Baradaran H, Kamel H, Pandya A, Mangla A, Dunning A, et al. Evaluation of computed tomography angiography plaque thickness measurements in high-grade carotid artery stenosis. Stroke. 2014;45(3):740\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNandalur KR, Hardie AD, Raghavan P, Schipper MJ, Baskurt E, Kramer CM. Composition of the stable carotid plaque: insights from a multidetector computed tomography study of plaque volume. Stroke. 2007;38(3):935\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"atherosclerosis, carotid plaque, calcified plaque, recurrent stroke","lastPublishedDoi":"10.21203/rs.3.rs-8507625/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8507625/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective:\u003c/h2\u003e \u003cp\u003eThe correlation between carotid plaque calcification types and recurrent stroke was investigated using computed tomography angiography (CTA). In addition, conjoint analysis was conducted to explore the physical activity, appetite, sleep and mood of the patients as variables, in order to provide new reference for the clinical treatment and management of ischemic stroke.\u003c/p\u003e\u003ch2\u003eMethod:\u003c/h2\u003e \u003cp\u003ePatients who underwent head and neck CTA scans and who were diagnosed with unilateral or bilateral carotid plaques with stenosis\u0026thinsp;\u0026lt;\u0026thinsp;70% at the First People\u0026rsquo;s Hospital of Lianyungang from September 2022 to August 2023 were enrolled in this study, with 2\u0026ndash;3 years of follow-up. Patients meeting the inclusion criteria were classified into 1\u0026ndash;6 types based on plaque calcification characteristics, in order to analyze differences in recurrent stroke between these types.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eUsing on the inclusion and exclusion criteria, 346 patients with carotid plaque were included. In the clinical baseline data, no statistically significant differences were observed between the recurrent and the non-recurrent stroke groups. Spearman\u0026rsquo;s correlation analysis revealed statistically significant associations between plaque calcification types and recurrent stroke (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Subsequently, Cox proportional hazards model analysis further demonstrated a significant correlation between plaque calcification types and clinical endpoint (HR: 1.149,95% CI: 1.059\u0026ndash;1.247, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Even after adjusting for sleep, appetite, physical activity and mood of the patients, the plaque calcification types remained significantly associated with the clinical endpoint (HR: 1.128,95% CI: 1.037\u0026ndash;1.226, p\u0026thinsp;=\u0026thinsp;0.005).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eThis study indicates a correlation between carotid plaque calcification types and the recurrence of stroke. These findings provide a new approach to studying carotid atherosclerotic plaque calcification and further imaging-based evidence for the risk assessment of recurrent ischemic stroke.\u003c/p\u003e","manuscriptTitle":"Study on the correlation between carotid plaque calcification types and the recurrence of ischemic stroke","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 16:50:59","doi":"10.21203/rs.3.rs-8507625/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-23T10:39:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-23T00:22:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T06:04:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"61435310469864504320392870819179634303","date":"2026-02-07T01:21:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164714651336671093825020753353556431172","date":"2026-02-02T05:03:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94470231352910011309317071331462334358","date":"2026-01-31T03:43:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-27T23:18:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170080952217517799734035775785724757735","date":"2026-01-27T14:36:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-27T13:21:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T13:19:07+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-19T08:03:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-17T10:03:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Imaging","date":"2026-01-17T09:56:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmim","sideBox":"Learn more about [BMC Medical Imaging](http://bmcmedimaging.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmim/default.aspx","title":"BMC Medical Imaging","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8dd0a625-72df-4aa7-9982-bcd785a4f623","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:27:03+00:00","versionOfRecord":{"articleIdentity":"rs-8507625","link":"https://doi.org/10.1186/s12880-026-02293-4","journal":{"identity":"bmc-medical-imaging","isVorOnly":false,"title":"BMC Medical Imaging"},"publishedOn":"2026-03-26 16:12:38","publishedOnDateReadable":"March 26th, 2026"},"versionCreatedAt":"2026-01-29 16:50:59","video":"","vorDoi":"10.1186/s12880-026-02293-4","vorDoiUrl":"https://doi.org/10.1186/s12880-026-02293-4","workflowStages":[]},"version":"v1","identity":"rs-8507625","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8507625","identity":"rs-8507625","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}