Mortality and Recurrence in Acute Ischemic Stroke of All Etiologies According to Ultrasonographic Assessment of Carotid and Aortic Arch Plaques: A Prospective Study.

Mortality and Recurrence in Acute Ischemic Stroke of All Etiologies According to Ultrasonographic Assessment of Carotid and Aortic Arch Plaques: A Prospective Study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mortality and Recurrence in Acute Ischemic Stroke of All Etiologies According to Ultrasonographic Assessment of Carotid and Aortic Arch Plaques: A Prospective Study. giuseppe miceli, Maria Grazia BASSO, Alessandra Casuccio, Andrea Roberta PENNACCHIO, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6172112/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Internal and Emergency Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Carotid duplex ultrasound helps to determine the degree of stenosis or occlusion and characterizes plaque composition and vulnerability, which is crucial for stroke risk stratification. Recurrent ischemic stroke poses a significant risk to individuals, with about one-third of stroke survivors experiencing a repeat event within five years. Older age, previous stroke or transient ischemic attack, atrial fibrillation, and large-artery atherosclerosis further increase the risk of recurrent strokes and influence prognosis. Moreover, stroke can result in worse outcomes, including higher morbidity, mortality, and cardiovascular complications in the three years after. This study aims to evaluate the link between ultrasound characteristics of aortic and carotid plaques and the risk of mortality and recurrent stroke among patients with acute ischemic stroke. One hundred-eight patients with first-episode acute ischemic stroke, a mean age of 71.3(13.4) years, underwent carotid Duplex and transthoracic aortic arch ultrasounds. They were followed up every 6 months for three years. The results revealed that while carotid plaques and stenosis were not significantly associated with recurrent stroke, the absence of plaques was related to higher survival rates (p = 0.008). Conversely, the simultaneous presence of plaques in both common and internal carotids was associated with increased mortality (p = 0.004). Finally, echo-lucent intimal lesions, according to the Gray-Weale classification considered high-risk plaque, showed good sensitivity (89.6%) but poor specificity in predicting outcomes at 3 years (AUC = 0.63, p = 0.0164). These findings suggest that routine non-invasive ultrasound evaluation of both carotid and aortic arch can be beneficial in stratifying patients for secondary prevention and improving stroke care. atherosclerosis aortic atheroma carotid plaque recurrent stroke Figures Figure 1 1. INTRODUCTION Stroke represents a leading cause of death and disability worldwide, with atherosclerosis of the carotid artery representing a primary risk factor for its development [ 1 ]. Carotid Duplex Ultrasound (CDU) evaluation is crucial in the diagnostic and etiological framework of ischemic stroke (IS), providing valuable information on the underlying vascular pathology and helping in clinical management decisions [ 2 ]. Additionally, ultrasound imaging allows the assessment of plaque composition according to echogenicity Gray-Weale classification, and vulnerability, which can help stratify stroke risk and guide appropriate interventions, including carotid endarterectomy or stenting [ 3 ]. Furthermore, CDU provides hemodynamic information by measuring blood flow velocities, allowing the detection of abnormal flow patterns associated with arterial stenosis or occlusions. Overall, CDU is useful as a noninvasive and easily accessible tool to evaluate large-vessel causes of ischemic stroke, facilitating timely diagnosis and targeted therapeutic interventions to mitigate the risk of recurrent cerebrovascular events [ 4 ]. IS recurrence represents a significant threat to individuals who have experienced a cerebrovascular event, amplifying the risks of disability and mortality. After a first acute IS, the likelihood of subsequent strokes increases substantially, with estimates suggesting that up to one-third of stroke survivors experience a recurrent event within five years [ 5 ]. This elevated risk highlights the importance of comprehensive secondary prevention strategies, including aggressive management of modifiable risk factors such as hypertension, diabetes, hyperlipidemia, and smoking cessation. Furthermore, the presence of some clinical factors, such as advanced age, a previous history of stroke or transient ischemic attack (TIA), atrial fibrillation, and atherosclerosis of large arteries, further increases the risk of recurrent ischemic events and mortality [ 5 ]. Importantly, IS can be associated with worse outcomes, including increased morbidity and mortality rates. The recurrent events not only aggravate neurological damage but also contribute to a higher risk of cardiovascular complications and overall mortality [ 6 ]. Recently, carotid and aortic arch (AA) atherosclerotic plaques have been demonstrated to be significant predictors of recurrent stroke (RS) and other vascular events [ 7 ]. Atheroembolic stroke may be linked to plaque in the AA. Although transesophageal echocardiography (TEE) can identify AA plaques, it is invasive. Recently, a new noninvasive technique has been developed using transcutaneous real-time B-mode ultrasonography with color flow duplex [ 8 ]. This method has been validated in numerous studies, demonstrating high accuracy in identifying complex aortic arch plaques compared to TEE [ 9 – 10 ]. Interestingly, according to the 2024 ESC Guidelines for Peripheral Arterial and Aortic Diseases (PAAD) [ 11 ], AA plaques are considered within the context of systemic atherosclerosis, and their management aligns with overall preventive strategies for peripheral arterial and aortic diseases, which include aggressive cardiovascular risk reduction through pharmacological and lifestyle measures​. Consequently, there is growing interest in the impact of aortic atheromas on the prognosis and stratification of high-risk patients. This study aims to evaluate the associations between the clinical and ultrasound characteristics of carotid and aortic arch plaques and the risk of mortality and recurrent strokes in a cohort of patients presenting with a first episode of acute ischemic stroke. 2. MATERIALS AND METHODS All consecutive patients with a clinical diagnosis of acute IS confirmed by brain computed tomography (CT) or magnetic resonance imaging (MRI), were admitted to the Unit of Internal Medicine with Stroke Care at the University Hospital “P. Giaccone” in Palermo, Italy, from March 2019 to January 2021, were recruited for the study. The study protocol was conducted in accordance with the 1975 Helsinki Declaration. The local Ethics Committee approved the study protocol and all patients consented to the study protocol by signing a written informed consent. Patients with a history of previous transient ischemic attack or ischemic or previous hemorrhagic stroke were excluded from the study. Furthermore, patients with acute hemorrhagic stroke were also excluded. Ischemic stroke was defined as an episode of neurologic deficit lasting > 24 hours or clinical symptoms where MRI or CT showed infarctions related to the clinical findings [ 12 ]. All patients underwent CDU and a second-harmonic transthoracic-color-Doppler ultrasound of the aortic arch through the suprasternal window and a 3-year follow-up, monitoring compliance with the prescribed therapy and the occurrence of new events such as recurrent stroke or death. CDU was performed with a Philips IU 22 ultrasound machine using a linear probe (5–12 Mhz) in a quiet, noise-free environment. The examination was conducted with the patient supine and neck extended, evaluating all the main arteries of the neck in the short and long axis: common carotid, internal and external carotid, vertebral in all its explorable sections (V0, V1, V2, and V3), brachiocephalic trunk and subclavian artery. Each vessel was evaluated in B-mode, color module, and Doppler. Intimal medial thickening (IMT) was measured in the posterior wall of the common carotid artery approximately 1 cm away from the carotid bifurcation in an area free from intimal lesions. The carotid walls were considered thickened for IMT values ​​greater than 1 mm. The carotid intimal plaque was defined as a formation with a thickness greater than or equal to 1.5 mm or 50% greater than the IMT measured ipsilaterally in accordance with the Mannheim consensus [ 13 ]. For each carotid lesion the following were evaluated: localization, eccentricity or concentricity, regularity of the margins and presence of ulcerations, and echogenicity according to the Gray-Weale classification, thickness, and stenosis [ 14 ]. The Gray-Weale classification is used in carotid ultrasound to evaluate the characteristics of carotid plaques, particularly their echogenicity, which may indicate the risk of cerebrovascular events. This classification divides plaques into five main types, based on their ultrasound composition: Type 1: Uniform, hypoechoic (low echogenicity) plaque. These plaques are mainly lipid and are considered at high risk of rupture and, therefore, ischemic events. Type 2: Predominantly hypoechoic plaque with some hyperechoic areas (higher echogenicity). These plaques have a mixture of lipid and fibrous tissue. Type 3: Predominantly hyperechoic plaque with some hypoechoic areas. These are mainly fibrous but also contain some lipid elements. Type 4: Uniform, hyperechoic plaque. These plaques are generally considered less vulnerable to rupture than hypoechoic types. Type 5: Calcific plaque. These plaques have high quantities of calcium which can determine the presence of shadow cone artifact, hindering the visualization of the vessel and the evaluation of the stenosis. To evaluate the AA using the second harmonic, the same Philips IU 22 ultrasound machine was employed with a sector array transducer probe (1–5 MHz). The transducer was positioned in the jugulus or the supraclavicular fossa and angled to obtain a long-axis view of the complete AA. Views of the ascending aorta and proximal arch were obtained by anterior tilting of the transducer; views of the distal arch and descending thoracic aorta were obtained by tilting the transducer posteriorly. Particular attention was paid to identifying the origin of the three main branches of the aorta. The AA was scanned systematically using acoustic zoom intermittently to facilitate detail recognition and adjust the gain to optimize the signal-to-noise ratio [ 8 ]. The examination results were classified as follows: 1) absence of significant atherosclerotic lesions (a normal arch or only intimal thickening < 1mm); 2) presence of aortic arch atheromas (AAA) protruding into the lumen or presence of a mobile component [ 7 ]. Both examinations were performed by a single experienced operator blinded to the participant’s characteristics and risk factors. At the time of the visit, all patients underwent routine blood chemistry tests, blood pressure measurements, and global cardiovascular risk assessment. Early management of stroke and the risk factors such as blood pressure, cholesterol, diabetes, and choice of antiplatelet therapy was conducted following American Stroke Association guidelines [ 15 ]. Subsequently, the patients were monitored through a six-month telephone follow-up conducted by two physicians for 3 years to identify compliance with therapy and state of health. Moreover, the physicians assessed the possible occurrence of events (mortality for all causes and RS) via structured telephone interviews directly with the patients or, when necessary, with their close family members. Follow-up started at the baseline examination and lasted until June 1, 2024. Of all participants in the present study, 2 (1,1%) were lost to follow-up. For these subjects, the follow-up time was computed until the last date of contact. Two research physicians reported fatal and recurrent stroke events. Research assistants verified all information by checking medical records. A supervisor researcher checked all participants’ medical records annually for possible missed events. Letters and, in case of hospitalization, discharge reports from medical specialists were obtained. Concerning the vital status of participants, information was also obtained regularly by telephone contact with the general practitioners. After notification, the cause and circumstances of death were established by a questionnaire from the general practitioners. Finally, a medical expert in stroke and cardiovascular disease, whose judgment was considered final, reviewed all events 3. STATISTICAL ANALYSIS The sample size was estimated to detect a ± 10% difference both for discrete and parametric variables between the patients with different outcomes (recurrent stroke and mortality), considering a patient dropout of 5%. The sample size of 74 patients was calculated to provide 80% power with α = 0.05. Statistical analysis of quantitative and qualitative data, including descriptive statistics, was performed for all items. Continuous data are expressed as mean ± SD unless otherwise specified. Frequency analysis was performed using Pearson’s chi-square test and Fisher exact test, as needed. The t-Student test and one-way analysis of variance (ANOVA) were performed for parametric variables to evaluate the associations between demographic, clinical, laboratory, and ultrasound characteristics with outcomes of patients at 3 years (recurrent stroke and mortality). Furthermore, multinomial logistic regression analysis examined the relationship between demographic, clinical, and ultrasound variables (dependent variables) and mortality at 3 years (independent variable). Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. To assess the predictive rate of the Gray-Weale score in 3-year mortality, a receiver operating characteristic (ROC) curve, with calculations of the area under the curve and 95% CI, was constructed, and sensitivity and specificity values were calculated. The data were analyzed using IBM SPSS Software version 24 (IBM Corp., Armonk, NY, USA). All p values were two-tailed, and p ≤ 0.05 was considered to indicate statistical significance. 4. RESULTS A total of 114 patients were recruited. Four patients were excluded because of insufficient transthoracic AA image quality. Two patients who did not complete follow-up were excluded from the analysis. 108 patients completed the three-year study, 50 females and 58 males with an average age of 71.3±13.4 years, twenty-one patients (24%) suffered an RS. Twenty-nine patients (26%) died during the three-year follow-up. Demographic, clinical, and laboratory variables of patients without and with RS at 3 years are shown in Table 1 a. No statistically significant differences were observed in the use of antiplatelet therapy, anticoagulant therapy, or the absence of treatment between patients with and without atherosclerosis of the aortic arch and carotid arteries. Demographic, clinical, and laboratory variables of patients according to 3-year mortality are shown in Table 1 b. Patients who did not experience RS were more likely to present lower systolic blood pressure at enrollment than those with a subsequent stroke (139.2±24.2 vs 152.1±36.3; p = 0.05 . Patients who experienced fatal outcomes were more likely to present: older age (67.8±12.9 vs 80.8 ±10.1; p < 0.0001 ), higher heart rate (77.5±12.3 vs 84.4±15.4; 0.017), lower HDL cholesterol levels (45.6±14.5 vs 38.6±13.7; p = 0.027 ), and elevated creatinine (1.1±0.4 vs 1.4±1.1; p = 0.041 ). Risk factors and comorbidities are presented in supplemental Tables 1a and 1b. Smoking history was associated with 3-year mortality ( p = 0.021 ; Table 2 b). Atrial fibrillation ( p = 0.032 ) and no antiplatelet administered within 48 hours of the onset of stroke symptoms ( p = 0.021 ) were associated with mortality (Supplemental Tables 1b and 2b). Moreover, poor compliance with antiplatelet therapy ( p = 0.001 ) and statin therapy ( p = 0.024 ) was also statistically associated with augmented mortality (Supplemental Table 2b). The absence of carotid plaque was not statistically associated with a reduction risk of RS (Table 2 a) but was significantly related to three-year survival ( p = 0.008 , Table 2 b). Carotid stenosis was not statistically associated with nether RS (Table 4a) and mortality (Table 2 b). AAA alone was not significantly associated with stroke recurrence ( p = 0.777 ) and mortality ( p = 1.0 ), as shown in Tables 2 a and 2 b. The simultaneous presence of atherosclerotic plaques in both the internal and common carotid arteries was not statistically associated with RS (Table 2 a) but was significantly associated with mortality ( p = 0.004 ; Table 2 a). The simultaneous presence of atherosclerotic plaques in both carotid and AA was not statistically associated with RS and mortality (Tables 2 a and 2 b). Moreover, the absence of plaques in both carotid and AA was not associated with RS (Table 2 a). Still, it was significantly associated with lower mortality ( p = 0.039 ; Table 2 b). Unsurprisingly, echo-lucent intimal lesions, according to the Gray-Weale classification (Type 1 and 2), considered high-risk plaque (HRP), showed good sensitivity (89.6%) but poor specificity in predicting outcomes at 3 years (AUC = 0.63, p = 0.0164) (Fig. 1). On multinomial regression analysis, age and presence of HRP were statistically correlated with 3-year mortality, albeit the latter in a weakly significant manner (Table 3 ). Association between the stroke characteristics with RS and 3-year mortality are reported in Supplemental Tables 3a and 3b. Antiplatelet and anticoagulant therapy’s association with the two outcomes is reported in Supplemental Tables 4a and 4b. Table 1 a. Descriptive analysis population: comparison between demographic, clinical, and laboratory variables of patients without and with recurrent stroke at 3 years (mean ±SD). VARIABLES NRS (n = 87; 80%) Rs (N = 21; 24%) TOTAL (n = 108) p Age mean 70.3 ±14.3 75.5±8.3 71.3±13.4 0.111 DAP at admission 77.5±18.4 80.2±20.6 78.1±18.8 0.554 SAP at admission 139.2±24.2 152.1±36.3 141.7±27.3 0.050 HR at admission 78.8±13.3 81.8±14.2 79.4±13.5 0.360 Total cholesterol 161.8±54.1 163.3±43.9 162.1±52.1 0.905 HDL cholesterol 44.6±14.7 40.1±13.8 43.7±14.5 0.212 Triglyceride 126.6±89.6 117.2±37.9 124.8±82.1 0.640 LDL cholesterol 96.9±45.6 95.9±40.7 96.7±44.5 0.935 WBC 10266.9±4755.4 9402.4±2976.1 10098.8±4466.5 0.429 Creatinine 1.2±0.7 1.2±0.6 1.2±0.7 0.873 Proteinuria 53.3±162.8 18.4±26.9 46.5±147.1 0.332 CRP 30.8±54.9 31.7±40.3 31.0±52.2 0.944 eGFR 173.7±1003.4 64.1±24.1 152.4±900.7 0.619 IMT mean 0.9±0.2 0.9±0.2 0.9±0.2 0.215 CRP: C reactive protein; DAP: diastolic arterial pressure; eGFR: estimated glomerular filtration rate; HR: heart rate; IMT: intima-media thickening; NRS: No recurrent stroke; RS: recurrent stroke; SAP: systolic arterial pressure; WBC: white blood cells. Table 1 b. Descriptive analysis of the population: comparison between demographic, clinical, and laboratory variables of patients without and with exitus at 3 years (mean ±SD) VARIABLES NO EXITUS (n = 79; 80%) EXITUS (n = 29; 26%) TOTAL (n = 108) p Age mean 67.8±12.9 80.8±10.1 71.3±13.5 0.0001 DAP at admission 80.9±19.8 70.3±13.4 78.1±18.8 0.009 SAP at admission 144.1 ± 27.2 135.0 ± 26.8 141.7±27.3 0.126 HR at admission 77.5±12.3 84.5±15.4 79.4±13.5 0.017 Total cholesterol 162.9±51.5 160.1±54.4 162.1±52.1 0.806 HDL cholesterol 45.6±14.5 38.6±13.7 43.7±14.5 0.027 Triglyceride 127.9±84.5 116.5±76.1 124.8±82.1 0.527 LDL cholesterol 95.9±43.7 98.9±47.4 96.7±44.5 0. 756 WBC 10292.3±4457.9 9571.7±4525.6 10098.8±4466.5 0.460 Creatinine 1.1±0.4 1.4±1.1 1.2±0.7 0.041 Proteinuria 54.5±170.6 24.7±31.2 46.5±147.1 0.352 CRP 25.6±52.4 45.7±49.7 31.0±52.2 0.076 eGFR 187.3±1052.6 57.4±25.4 152.4±900.7 0.509 IMT mean 0.9±0.2 0.9±0.2 0.9±0.2 0.110 CRP: C reactive protein; DAP: diastolic arterial pressure; eGFR: estimated glomerular filtration rate; HR: heart rate; IMT: intima-media thickening; SAP: systolic arterial pressure; WBC: white blood cells. Table 2a. Ultrasound characteristics and recurrent stroke at 3 years; N° (%) . NRS ( n=87) RS ( n=21) p ARCH AORTIC PLAQUES No (n=83) YES (n=25) 66 (80%) 21 (84%) 17 (20%) 4 (16%) 0.777 ABSENCE OF both AORTIC AND CAROTID PLAQUES NO (n=95) Yes (n=13) 78 (82%) 10 (77%) 17 (18%) 3 (23%) 0.725 Grey Weale score NO PLAQUES (n=16) hypoechoic/predominantly hypoechoic PLAQUES (type 1 and 2) (n=16) predominantly hyperechoic/hyperechoic/ Calcific plaques (type 3, 4 and 5) (n=76) 12 (75%) 14 (88%) 61 (80%) 4 (25%) 2 (12%) 15 (20%) 0.695 PRESENCE OF BOTH AORTIC AND CAROTID PLAQUES No (n=85) YES (n=23) 70 (82%) 19 (82%) 15 (28%) 4 (28%) 0.387 HEMODYNAMIC STENOSIS No (n=83) carotid stenosis (n=23) intracranial stenosis (n=2) 67 (81%) 18 (78%) 2 (100%) 16 (19%) 5 (22%) 0 (0%) 0.853 irregular surface no (n=102) yes (n=6) 82 (80%) 5 (83%) 20 (20%) 1 (17%) 1.0 PLAQUE LOCALISATION No plaques (n=15) ica (n=31) cca (n=27) mca (n=1) dCl (n=34) 11 (73%) 24 (77%) 23 (85%) 1 (100%) 28 (82%) 4 (27%) 7 (33%) 4 (15%) 0 (0%) 6 (18%) 0.807 CCA: common carotid artery; DCL: double Carotid localization (Common and Internal Carotid; ICA: internal carotid artery; MCA: middle cerebral artery. Table 2b. Ultrasound charateristics and exitus at 3 years; N° (%) . NO EXITUS ( n=79) EXITUS ( n=29) p ARCH AORTIC PLAQUES No (n=83) YES (n=25) 61 (73%) 18 (72%) 22 (27%) 7 (28%) 1.0 ABSENCE OF both AORTIC AND CAROTID PLAQUES NO (n=95) Yes (n=13) 66 (70%) 13 (100%) 29 (30%) 0 (0%) 0.039 Grey Weale score NO CAROTID PLAQUES (n=16) hypoechoic/predominantly hypoechoic PLAQUES(n=16) predominantly hyperechoic/hyperechoic/ Calcific plaques (n=76) 16 (100%) 13 (81%) 50 (66%) 0 (0%) 3 (19%) 26 (34%) 0.008 PRESENCE OF BOTH AORTIC AND CAROTID PLAQUES No (n=85) YES (n=23) 63 (74%) 16 (70%) 22 (26%) 7 (30%) 0.662 HEMODYNAMIC STENOSIS no (n=83) carotid stenosis (n=23) intracranial stenosis (n=2) 63 (76%) 14 (61%) 2 (100%) 20 (24%) 9 (39%) 0 (0%) 0.242 irregular surface No (n=102) yes (n=6) 75 (74%) 4 (67%) 27 (26%) 2 (33%) 0.658 PLAQUE LOCALIZATION No plaques (n=15) ica (n=31) cca (n=27) mca (n=1) dCl (n=34) 15 (100%) 23 (74%) 22 (81%) 1 (100%) 18 (53%) 0 (0%) 8 (26%) 5 (19%) 0 (0%) 16 (57%) 0.004 CCA: common carotid artery; DCL: double Carotid localization (Common and Internal Carotid) ; ICA: internal carotid artery; MCA: middle cerebral artery. Table 3 Multinomial regressions for mortality taking into account clinical and ultrasound variables adding age and sex as covariates EXITUS Follow-up at 3 years a HR 95% confidence interval for HR Lower limit Upper limit Sign. Mean age 1.122 1.053 1.197 0.0001 Sex 0.571 0.189 1.728 0.321 Mean IMT 0.985 0.050 19.329 0.992 Arch aortic plaques 0.527 0.157 1.770 0.300 Hemodynamic stenosis 1.045 0.317 3.438 0.943 Irregular surface 1.327 0.136 12.955 0.808 Plaque localisation 1.276 0.830 1.962 0.267 GRAY-WEALE score 1 or 2 3.702 0.952 14.405 0.059 a reference: no exitus at 3 years; HR = hazard ratio 5. DISCUSSION This study demonstrated an association between 3-year all-cause mortality and ultrasonographic characteristics of carotid and AAA in patients with acute IS of all etiologies. Firstly, our data showed that 24% of patients experienced an RS, and 26% died during the three-year follow-up period. Surprisingly, the simultaneous presence of atherosclerotic plaques in the internal or common carotid artery was significantly associated with higher mortality, instead, the simultaneous absence of atherosclerotic plaque in both carotid and AA was strongly related to lower mortality. These results suggest that the extent and characteristics of atherosclerotic disease may be more predictive of overall survival. For years, CDU has been a routine examination performed early in patients with ischemic stroke to evaluate, within 24 hours [ 4 ], to detect possible treatable and reversible vascular causes of the stroke and to estimate the patient's cardiovascular risk. The approach to the carotid vessels was preferred because it represented one of the simplest and quickest districts to explore. Furthermore, the carotid arteries’ size and their course ensure excellent sensitivity and specificity for evaluating atherosclerotic intimal lesions and estimating the patients' cardiovascular risk. Recently, the development of ultrasound equipment and its wider diffusion has led to the possibility of extending the study to the districts upstream and downstream of the carotid and vertebral arteries. The transcranial Doppler and color Doppler study of intravascular circulation has been shown to add valuable diagnostic information capable of modifying the management of patients with acute IS [ 16 ]. Similarly, extending the ultrasonological evaluation to the AA allowed for the addition of crucial information for the prognostic stratification of high-risk patients. The AA, due to its anatomical and pressure characteristics, represents a district at high risk of atherosclerotic appositions [ 17 ]. The presence of intimal lesions in the AA, as demonstrated by tomographic studies, represents an underestimated cause of embolic stroke of undetermined stroke (ESUS) and RS [ 18 – 19 ]. Furthermore, the development of AAA seems to be linked to specific groups of alleles in mice [ 20 ], supporting the hypothesis of involvement of distinct pathological processes at different vascular locations. Current guidelines for the prevention of stroke in patients with stroke and transient ischemic attack by the American Heart Association [ 21 ] highlighted the importance of AAA detection and suggested intensive lipid management to LDL < 70 mg/dl and antiplatelet therapy to prevent RS in these patients. Our study suggests that the co-presence of carotid and AAA could be an expression of a higher cardiovascular risk than the single localizations alone. Therefore, extending the routine study of the carotids to the evaluation of the AA could lead to a more complete and efficient estimation and understanding of the cardiovascular risk of patients with acute IS, as demonstrated by our results in line with the latest evidence. The French Study of Aortic Plaque in Stroke Group showed that the presence in the AA of plaques > 4 mm thick was a strong independent predictor of vascular events of all types [ 7 ]. Our data also demonstrate that the absence of carotid and AA atherosclerosis was a strong predictor of survival, confirming the importance of the aortic arch district in estimating patients’ prognosis. In clinical practice, greater importance is given to the presence of atherosclerosis in the internal carotid alone. Interestingly, our data demonstrate instead that the co-presence of intimal lesions in the common carotid is a piece of information that should be taken into account in the estimation of cardiovascular risk and patient prognosis. Unsurprisingly, in our population, the main risk factors for generalized atherosclerosis, such as age, lower HDL cholesterol levels, and elevated creatinine levels, were also significantly associated with mortality. Prospective studies have found an increased RS rate among patients with aortic plaques ≥ 4 mm in thickness, particularly with ulceration or mobile components [ 22 ] or without plaque calcifications [ 23 ]. In our population, AAA alone was not significantly associated with RS, perhaps because of the small sample and because we decided not to subdivide our population according to the thickness of the AAA. This choice was dictated by the desire not to further subdivide the population and reduce the power of statistical analysis. Furthermore, we wanted to demonstrate that the determination of the presence or absence of an atherosclerotic lesion, being a more reproducible data and less influenced by intra and inter-operator variability than the measurement of thickness, can represent a simple tool for the prognostic estimation of patients with IS. There are several possible explanations for our mortality data. First, aortic atherosclerosis is known to be strongly associated with arterial stiffness and augmented aortic pulse wave velocity [ 24 ]. As proposed by Fazekas et al. [ 25 ], and recently described by Saji et al. [ 26 ], elevated pulse wave velocity may contribute to cerebral microcirculatory damage, potentially leading to disrupted vascular dynamics and impaired perivascular flow, which can result in white matter lesions in the brain and glomerular damage in the kidneys. Additionally, an AAA may serve as a marker of widespread atherosclerosis rather than being solely a causative factor in subclinical cerebrovascular and cardiovascular disease. In the only community-based study, the Stroke Prevention: Assessment of Risk in a Community (SPARC) study, researchers found that 86% of patients with a history of TIA, stroke, or endarterectomy had an aortic plaque of any severity, compared to 49% of those without such a history [ 27 ]. Therefore, the absence of aortic and carotid lesions could be an expression of lower stiffness and a lower subclinical cardiovascular risk. Our data appear to be consistent with the results of two other prospective studies with a reasonable follow-up period, one from Ferrari et al. [ 28 ] and the other from Kazui et al. [ 29 ]. The authors found a major risk of death from stroke or peripheral embolism. Interestingly, in the latter study, lacunar stroke patients were prevalent, suggesting that the investigation and prevention should be directed at all potential causes of future strokes. According to our results, high-risk plaques, as classified by the Gray-Weale system, provide valuable prognostic information for long-term survival but are less predictive of RS. Moreover, echo-lucent intimal lesions classified as HRP according to the Gray-Weale classification (Type 1 and 2) showed good sensitivity (89.6%) but poor specificity in predicting outcomes at three years (AUC = 0.63, p = 0.0164). Echolucent plaques, particularly the juxta luminal black plaque area, which may represent a thrombus, indicate a higher stroke risk. In a fascinating study [ 33 ] conducted on 324 patients with 50–99% carotid stenosis increasing stenosis, gray scale median (GSM) ≤ 15 and juxtaluminal black plaque area ≥ 8 mm 2 were independent predictors of the presence of hemispheric symptoms and allowed to stratify a high-risk group. In our multivariate analysis, age and the presence of HRP were statistically correlated with three-year mortality. This reinforces the idea that age and specific plaque characteristics, including echogenicity and localization, rather than the presence of stenosis alone, are critical factors in determining long-term outcomes in stroke patients. Interestingly, while the absence of carotid plaque and AA was not significantly associated with RS risk, it was significantly related to three-year survival, in agreement with recent studies performing CDU. In a prospective study conducted for 34 months on a sample of 541 patients, the authors highlighted that Kaplan-Meier survival estimates have shown the best outcome in patients without carotid plaque [ 30 ]. Furthermore, the carotid plaque score recently proposed to predict the risk of cerebral ischemic events and global cardiovascular risk has shown that a score lower than 3, which includes patients who have no carotid plaque or few small plaques, is associated with the lowest risk profile with reduced mortality [ 31 ]. In 2004, the Rotterdam study demonstrated how non-invasive assessment of extra-coronary atherosclerosis was an excellent predictor of acute myocardial infarction, even fatal. In particular, the co-presence of aortic plaques highlighted by chest X-ray and carotid or lower limb plaques determined a significant increase in risk, proportional also to the severity of the stenosis [ 32 ]. Our study, corroborating these results and proposing the routine use of transthoracic AA evaluation to complement carotid evaluation, keeps pace with technological advances in ultrasound. It is also proposed as a new modus operandi for the ultrasound-based prognostic stratification of patients with IS potentially translatable to all high-risk populations. 6. LIMITATION OF THE STUDY Our study surely presents several limitations. First, the small sample size did not allow us to stratify our population based on aortic arch plaque thickness. Our study aimed not to assess the embolic potential of the plaque itself but to evaluate the contribution of aortic arch assessment in estimating the overall cardiovascular and cerebrovascular risk in these patients. Second, we included all the main subtypes of IS (cardioembolic, associated with large vessel disease, small vessel disease, and cryptogenic). Still, we did not individually evaluate the impact of carotid and AA atherosclerosis for each etiology. At the same time, this allows us to generalize our results to all stroke subtypes and, in the future, to translate the results to other populations at high cardiovascular risk. Third, we did not perform a specific analysis of risk based on therapy (anticoagulant and antiplatelet), but our study was not designed to be a therapeutic trial. Fourth, we did not reevaluate with ultrasound follow-up the evolution of atherosclerotic lesions identified at baseline, but our study aimed to evaluate the combined prognostic power of carotid and aortic arch ultrasound in risk stratification at the time of the first cerebral ischemic event. 7. CONCLUSIONS This study demonstrates that the simultaneous absence of carotid and aortic arch plaques is a significant predictor of survival in patients with acute stroke. Conversely, the presence of high-risk atherosclerotic lesions (Gray-Weale types 1 e 2), along with the simultaneous presence of plaques in the common and internal carotid, is associated with higher mortality. These insights testify to the importance of adapting the screening of cardio and cerebrovascular risk to the new ultrasonographic technological potential through non-invasive ultrasonic evaluation of the aortic arch. Incentivizing the large and routine use of ultrasound evaluation of the carotid and the aortic arch in patients with acute ischemic stroke can guide future studies to stratify better patients for secondary prevention strategies to enhance the quality of care for stroke survivors. Abbreviations AA: aortic arch; AAA: aortic arch atheromas; CDU: Carotid Duplex Ultrasound; CT: computed tomography; ESUS: embolic stroke of undetermined stroke; HRP: high-risk plaque; IMT: Intimal medial thickening; IS: ischemic stroke; MRI: magnetic resonance imaging; RS: recurrent strokes; TIA: transient ischemic attack; TEE: transesophageal echocardiography. Declarations Conflict of interests: All authors declare that they have no competing interests. Financial support None Availability of data and materials: The data and images used in the current study are available from the corresponding author upon reasonable request. Author Contributions Giuseppe Miceli : Conceptualization, Methodology, project administration, writing-original draft; Maria Grazia Basso : investigation, data curation; Alessandra Casuccio : methodology, formal analysis, writing-review and editing; Chiara Pintus : investigation; Andrea Roberta Pennacchio : investigation, data curation; Elena Cocciola : investigation; Mariagiovanna Cuffaro : investigation; Martina Profita : investigation; Giuliana Rizzo : investigation; Antonino Tuttolomondo : project administration, writing-review and editing, supervision. Acknowledgments: We thank the Italian Society of Neurosonology and Cerebral Hemodynamic (SINSEC) group for training, education, and general supervision of the research group. References Katan M, Luft A. Global burden of stroke. Semin Neurol 2018;38: 208-1. Chanhung Z. Lee, Steven W. Hetts, Interventional Neuroradiology Anesthetic Management, Cottrell & Patel's Neuroanesthesia, (272-290), (2025).https://doi.org/10.1016/B978-0-323-93273-8.00014-6 Gray-Weale AC, Graham JC, Burnett JR, Byrne K, Lusby RJ. Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology. J Cardiovasc Surg (Torino). 1988 Nov-Dec;29(6):676-81. PMID: 3062007. Nezu T, Hosomi N. Usefulness of Carotid Ultrasonography for Risk Stratification of Cerebral and Cardiovascular Disease. J Atheroscler Thromb. 2020 Oct 1;27(10):1023-1035. doi: 10.5551/jat.RV17044. Epub 2020 Aug 29. PMID: 32863299; PMCID: PMC7585913. Flach C, Muruet W, Wolfe CDA, Bhalla A, Douiri A. Risk and Secondary Prevention of Stroke Recurrence: A Population-Base Cohort Study. Stroke. 2020 Aug;51(8):2435-2444. doi: 10.1161/STROKEAHA.120.028992. Epub 2020 Jul 10. PMID: 32646337 Khanevski AN, Bjerkreim AT, Novotny V, Naess H, Thomassen L, Logallo N, Kvistad CE; NOR-STROKE study group. Recurrent ischemic stroke: Incidence, predictors, and impact on mortality. Acta Neurol Scand. 2019 Jul;140(1):3-8. doi: 10.1111/ane.13093. Epub 2019 Apr 11. PMID: 30929256 French Study of Aortic Plaques in Stroke Group; Amarenco P, Cohen A, Hommel M, Moulin T, Leys D, Bousser M-G. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med. 1996 May 9;334(19):1216-21. doi: 10.1056/NEJM199605093341902. Kinnaman KA, Kimberly HH, Pivetta E, Platz E, Chudgar A, Adduci A, Stone MB, Rempell JS. Evaluation of the Aortic Arch from the Suprasternal Notch View Using Focused Cardiac Ultrasound. J Emerg Med. 2016 Apr;50(4):643-50.e1. doi: 10.1016/j.jemermed.2015.12.002. Epub 2016 Jan 29. Weinberger J. Noninvasive imaging of atherosclerotic plaque in the arch of the aorta with transcutaneous B-mode ultrasonography. 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Eur Heart J. 2024 Sep 29;45(36):3538-3700. doi: 10.1093/eurheartj/ehae179 Johnson CJ, Kittner SJ, McCarter RJ, Sloan MA, Stern BJ, Buchholz D, Price TR. Interrater reliability of an etiologic classification of ischemic stroke. Stroke. 1995 Jan;26(1):46-51. doi: 10.1161/01.str.26.1.46. PMID: 7839396. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Hernandez Hernandez R, Jaff M, Kownator S, Naqvi T, Prati P, Rundek T, Sitzer M, Schminke U, Tardif JC, Taylor A, Vicaut E, Woo KS. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34(4):290-6. doi: 10.1159/000343145. Epub 2012 Nov 1. PMID: 23128470; Steffen CM, Gray-Weale AC, Byrne KE, Lusby RJ. Carotid artery atheroma: ultrasound appearance in symptomatic and asymptomatic vessels. Aust N Z J Surg. 1989 Jul;59(7):529-34. doi: 10.1111/j.1445-2197.1989.tb01625.x. PMID: 2665710. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. Erratum in: Stroke. 2019 Dec;50(12):e440-e441. doi: 10.1161/STR.0000000000000215. PMID: 31662037. Wan Y, Teng X, Li S, Yang Y. Application of transcranial Doppler in cerebrovascular diseases. Front Aging Neurosci. 2022 Nov 8;14:1035086. doi: 10.3389/fnagi.2022.1035086. PMID: 36425321 Tomita H, Zhilicheva S, Kim S, Maeda N. Aortic arch curvature and atherosclerosis have overlapping quantitative trait loci in a cross between 129S6/SvEvTac and C57BL/6J apolipoprotein E-null mice. Circ Res. 2010 Apr 2;106(6):1052-60. doi: 10.1161/CIRCRESAHA.109.207175. Epub 2010 Feb 4. PMID: 20133902 Zavala JA, Amarrenco P, Davis SM, Jones EF, Young D, Macleod MR, Horky LL, Donnan GA. Aortic arch atheroma. Int J Stroke. 2006 May;1(2):74-80. doi: 10.1111/j.1747-4949.2006.00026.x. Boyko M, Chaturvedi S, Beland B, Najm M, Demchuk AM, Menon BK, Almekhlafi M. Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source. J Stroke Cerebrovasc Dis. 2023 Dec;32(12):107374. doi: 10.1016/j.jstrokecerebrovasdis.2023.107374. Epub 2023 Oct 7 Kayashima Y, Makhanova NA, Matsuki K, Tomita H, Bennett BJ, Maeda N. Identification of aortic arch-specific quantitative trait loci for atherosclerosis by an intercross of DBA/2J and 129S6 apolipoprotein E-deficient mice. PLoS One. 2015 Feb 17;10(2):e0117478. doi: 10.1371/journal.pone.0117478. PMID: 25689165 Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24. Erratum in: Stroke. 2021 Jul;52(7):e483-e484. doi: 10.1161/STR.0000000000000383. PMID: 34024117. Cohen, A, Tzourio, C, Bertrand, B, Chauvel, C, Bousser, MG, Amarenco, P. Aortic plaque morphology and vascular events: a follow-up study in patients with ischemic stroke: FAPS Investigators: French Study of Aortic Plaques in Stroke. Circulation . 1997;96:3838–3841. doi: 10.1161/01.cir.96.11.3838 Amarenco, P, Cohen, A, Hommel, M, Moulin, T, Leys, D, Bousser, MG. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med . 1996;334:1216–1221 van Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS, Hoeks AP, van der Kuip DA, Hofman A, Witteman JC. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke. 2001 Feb;32(2):454-60. doi: 10.1161/01.str.32.2.454. Fazekas F, Kleinert R, Offenbacher H, Payer F, Schmidt R, Kleinert G, Radner H, Lechner H. The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol. 1991 Sep-Oct;12(5):915-21. PMID: 1950921 Saji N, Toba K, Sakurai T. Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain? Pulse (Basel). 2016 Apr;3(3-4):182-9. doi: 10.1159/000443614. Epub 2016 Jan 20. PMID: 27195239; Agmon Y, Khandheria BK, Meissner I, Schwartz GL, Petterson TM, O'Fallon WM, Whisnant JP, Wiebers DO, Seward JB. Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population. Am J Cardiol. 2002 Feb 1;89(3):262-7. doi: 10.1016/s0002-9149(01)02225-1. PMID: 11809426.] Ferrari E, Vidal R, Chevallier T, Baudouy M. Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants. J Am Coll Cardiol. 1999 Apr;33(5):1317-22. doi: 10.1016/s0735-1097(99)00003-0. PMID: 10193733 Kazui S, Levi CR, Jones EF, Quang L, Calafiore P, Donnan GA. Lacunar stroke: transoesophageal echocardiographic factors influencing long-term prognosis. Cerebrovasc Dis. 2001;12(4):325-30. doi: 10.1159/000047729. PMID: 11721103. Petersen C, Peçanha PB, Venneri L, Pasanisi E, Pratali L, Picano E. The impact of carotid plaque presence and morphology on mortality outcome in cardiological patients. Cardiovasc Ultrasound. 2006 Mar 24;4:16. doi: 10.1186/1476-7120-4-16. PMID: 16563156 Ihle-Hansen H, Vigen T, Berge T, Walle-Hansen MM, Hagberg G, Ihle-Hansen H, Thommessen B, Ariansen I, Røsjø H, Rønning OM, Tveit A, Lyngbakken M. Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population. J Am Heart Assoc. 2023 Sep 5;12(17):e030739. doi: 10.1161/JAHA.123.030739. Epub 2023 Aug 23. PMID: 37609981 van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DA, Witteman JC. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation. 2004 Mar 9;109(9):1089-94. doi: 10.1161/01.CIR.0000120708.59903.1B. Epub 2004 Mar 1. PMID: 14993130. Griffin MB, Kyriacou E, Pattichis C, et al. Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms. J Vasc Surg 2010;52:69-76. 10.1016/j.jvs.2010.02.265 Supplementary Files suplementarytables.docx Cite Share Download PDF Status: Published Journal Publication published 25 Aug, 2025 Read the published version in Internal and Emergency Medicine → Version 1 posted Reviewers agreed at journal 21 Mar, 2025 Reviewers invited by journal 19 Mar, 2025 Editor assigned by journal 12 Mar, 2025 First submitted to journal 10 Mar, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-6172112","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":431188000,"identity":"2459359f-2ca0-4f51-a114-073351add6d5","order_by":0,"name":"giuseppe 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15:55:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6172112/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6172112/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11739-025-04088-x","type":"published","date":"2025-08-25T15:58:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79574223,"identity":"8d3d1a14-4f75-4f64-b911-f414e72a8804","added_by":"auto","created_at":"2025-03-31 11:09:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29152,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver Operating Characteristic curve of the predictive rate of Gray-Weale score in 3-year mortality.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6172112/v1/2dfcad3d6610c2468b3bc8db.jpg"},{"id":90345087,"identity":"431cee28-c387-485e-92ec-735ac61d40fd","added_by":"auto","created_at":"2025-09-01 16:09:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1230392,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6172112/v1/92bb9288-3323-4e1d-a84d-25b8dff3eabc.pdf"},{"id":79574222,"identity":"50765fca-01e4-4417-91e9-27ed0ee450f8","added_by":"auto","created_at":"2025-03-31 11:09:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":46957,"visible":true,"origin":"","legend":"","description":"","filename":"suplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6172112/v1/82b731633b957e5a27e6003a.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eMortality and Recurrence in Acute Ischemic Stroke of All Etiologies According to Ultrasonographic Assessment of Carotid and Aortic Arch Plaques: A Prospective Study.\u003c/p\u003e","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eStroke represents a leading cause of death and disability worldwide, with atherosclerosis of the carotid artery representing a primary risk factor for its development [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Carotid Duplex Ultrasound (CDU) evaluation is crucial in the diagnostic and etiological framework of ischemic stroke (IS), providing valuable information on the underlying vascular pathology and helping in clinical management decisions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Additionally, ultrasound imaging allows the assessment of plaque composition according to echogenicity Gray-Weale classification, and vulnerability, which can help stratify stroke risk and guide appropriate interventions, including carotid endarterectomy or stenting [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Furthermore, CDU provides hemodynamic information by measuring blood flow velocities, allowing the detection of abnormal flow patterns associated with arterial stenosis or occlusions. Overall, CDU is useful as a noninvasive and easily accessible tool to evaluate large-vessel causes of ischemic stroke, facilitating timely diagnosis and targeted therapeutic interventions to mitigate the risk of recurrent cerebrovascular events [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. IS recurrence represents a significant threat to individuals who have experienced a cerebrovascular event, amplifying the risks of disability and mortality. After a first acute IS, the likelihood of subsequent strokes increases substantially, with estimates suggesting that up to one-third of stroke survivors experience a recurrent event within five years [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This elevated risk highlights the importance of comprehensive secondary prevention strategies, including aggressive management of modifiable risk factors such as hypertension, diabetes, hyperlipidemia, and smoking cessation.\u003c/p\u003e \u003cp\u003eFurthermore, the presence of some clinical factors, such as advanced age, a previous history of stroke or transient ischemic attack (TIA), atrial fibrillation, and atherosclerosis of large arteries, further increases the risk of recurrent ischemic events and mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Importantly, IS can be associated with worse outcomes, including increased morbidity and mortality rates. The recurrent events not only aggravate neurological damage but also contribute to a higher risk of cardiovascular complications and overall mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, carotid and aortic arch (AA) atherosclerotic plaques have been demonstrated to be significant predictors of recurrent stroke (RS) and other vascular events [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Atheroembolic stroke may be linked to plaque in the AA. Although transesophageal echocardiography (TEE) can identify AA plaques, it is invasive. Recently, a new noninvasive technique has been developed using transcutaneous real-time B-mode ultrasonography with color flow duplex [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This method has been validated in numerous studies, demonstrating high accuracy in identifying complex aortic arch plaques compared to TEE [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Interestingly, according to the 2024 ESC Guidelines for Peripheral Arterial and Aortic Diseases (PAAD) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], AA plaques are considered within the context of systemic atherosclerosis, and their management aligns with overall preventive strategies for peripheral arterial and aortic diseases, which include aggressive cardiovascular risk reduction through pharmacological and lifestyle measures​. Consequently, there is growing interest in the impact of aortic atheromas on the prognosis and stratification of high-risk patients. This study aims to evaluate the associations between the clinical and ultrasound characteristics of carotid and aortic arch plaques and the risk of mortality and recurrent strokes in a cohort of patients presenting with a first episode of acute ischemic stroke.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cp\u003e All consecutive patients with a clinical diagnosis of acute IS confirmed by brain computed tomography (CT) or magnetic resonance imaging (MRI), were admitted to the Unit of Internal Medicine with Stroke Care at the University Hospital \u0026ldquo;P. Giaccone\u0026rdquo; in Palermo, Italy, from March 2019 to January 2021, were recruited for the study.\u003c/p\u003e \u003cp\u003e The study protocol was conducted in accordance with the 1975 Helsinki Declaration. The local Ethics Committee approved the study protocol and all patients consented to the study protocol by signing a written informed consent.\u003c/p\u003e \u003cp\u003ePatients with a history of previous transient ischemic attack or ischemic or previous hemorrhagic stroke were excluded from the study. Furthermore, patients with acute hemorrhagic stroke were also excluded. Ischemic stroke was defined as an episode of neurologic deficit lasting\u0026thinsp;\u0026gt;\u0026thinsp;24 hours or clinical symptoms where MRI or CT showed infarctions related to the clinical findings [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. All patients underwent CDU and a second-harmonic transthoracic-color-Doppler ultrasound of the aortic arch through the suprasternal window and a 3-year follow-up, monitoring compliance with the prescribed therapy and the occurrence of new events such as recurrent stroke or death. CDU was performed with a Philips IU 22 ultrasound machine using a linear probe (5\u0026ndash;12 Mhz) in a quiet, noise-free environment. The examination was conducted with the patient supine and neck extended, evaluating all the main arteries of the neck in the short and long axis: common carotid, internal and external carotid, vertebral in all its explorable sections (V0, V1, V2, and V3), brachiocephalic trunk and subclavian artery. Each vessel was evaluated in B-mode, color module, and Doppler. Intimal medial thickening (IMT) was measured in the posterior wall of the common carotid artery approximately 1 cm away from the carotid bifurcation in an area free from intimal lesions. The carotid walls were considered thickened for IMT values ​​greater than 1 mm. The carotid intimal plaque was defined as a formation with a thickness greater than or equal to 1.5 mm or 50% greater than the IMT measured ipsilaterally in accordance with the Mannheim consensus [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For each carotid lesion the following were evaluated: localization, eccentricity or concentricity, regularity of the margins and presence of ulcerations, and echogenicity according to the Gray-Weale classification, thickness, and stenosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The Gray-Weale classification is used in carotid ultrasound to evaluate the characteristics of carotid plaques, particularly their echogenicity, which may indicate the risk of cerebrovascular events. This classification divides plaques into five main types, based on their ultrasound composition:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eType 1: Uniform, hypoechoic (low echogenicity) plaque. These plaques are mainly lipid and are considered at high risk of rupture and, therefore, ischemic events.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eType 2: Predominantly hypoechoic plaque with some hyperechoic areas (higher echogenicity). These plaques have a mixture of lipid and fibrous tissue.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eType 3: Predominantly hyperechoic plaque with some hypoechoic areas. These are mainly fibrous but also contain some lipid elements.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eType 4: Uniform, hyperechoic plaque. These plaques are generally considered less vulnerable to rupture than hypoechoic types.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eType 5: Calcific plaque. These plaques have high quantities of calcium which can determine the presence of shadow cone artifact, hindering the visualization of the vessel and the evaluation of the stenosis.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eTo evaluate the AA using the second harmonic, the same Philips IU 22 ultrasound machine was employed with a sector array transducer probe (1\u0026ndash;5 MHz). The transducer was positioned in the jugulus or the supraclavicular fossa and angled to obtain a long-axis view of the complete AA. Views of the ascending aorta and proximal arch were obtained by anterior tilting of the transducer; views of the distal arch and descending thoracic aorta were obtained by tilting the transducer posteriorly. Particular attention was paid to identifying the origin of the three main branches of the aorta. The AA was scanned systematically using acoustic zoom intermittently to facilitate detail recognition and adjust the gain to optimize the signal-to-noise ratio [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The examination results were classified as follows: 1) absence of significant atherosclerotic lesions (a normal arch or only intimal thickening\u0026thinsp;\u0026lt;\u0026thinsp;1mm); 2) presence of aortic arch atheromas (AAA) protruding into the lumen or presence of a mobile component [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Both examinations were performed by a single experienced operator blinded to the participant\u0026rsquo;s characteristics and risk factors.\u003c/p\u003e \u003cp\u003eAt the time of the visit, all patients underwent routine blood chemistry tests, blood pressure measurements, and global cardiovascular risk assessment. Early management of stroke and the risk factors such as blood pressure, cholesterol, diabetes, and choice of antiplatelet therapy was conducted following American Stroke Association guidelines [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Subsequently, the patients were monitored through a six-month telephone follow-up conducted by two physicians for 3 years to identify compliance with therapy and state of health. Moreover, the physicians assessed the possible occurrence of events (mortality for all causes and RS) via structured telephone interviews directly with the patients or, when necessary, with their close family members. Follow-up started at the baseline examination and lasted until June 1, 2024. Of all participants in the present study, 2 (1,1%) were lost to follow-up. For these subjects, the follow-up time was computed until the last date of contact. Two research physicians reported fatal and recurrent stroke events. Research assistants verified all information by checking medical records. A supervisor researcher checked all participants\u0026rsquo; medical records annually for possible missed events. Letters and, in case of hospitalization, discharge reports from medical specialists were obtained. Concerning the vital status of participants, information was also obtained regularly by telephone contact with the general practitioners. After notification, the cause and circumstances of death were established by a questionnaire from the general practitioners. Finally, a medical expert in stroke and cardiovascular disease, whose judgment was considered final, reviewed all events\u003c/p\u003e"},{"header":"3. STATISTICAL ANALYSIS","content":"\u003cp\u003eThe sample size was estimated to detect a\u0026thinsp;\u0026plusmn;\u0026thinsp;10% difference both for discrete and parametric variables between the patients with different outcomes (recurrent stroke and mortality), considering a patient dropout of 5%. The sample size of 74 patients was calculated to provide 80% power with α\u0026thinsp;=\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eStatistical analysis of quantitative and qualitative data, including descriptive statistics, was performed for all items. Continuous data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD unless otherwise specified. Frequency analysis was performed using Pearson\u0026rsquo;s chi-square test and Fisher exact test, as needed. The t-Student test and one-way analysis of variance (ANOVA) were performed for parametric variables to evaluate the associations between demographic, clinical, laboratory, and ultrasound characteristics with outcomes of patients at 3 years (recurrent stroke and mortality). Furthermore, multinomial logistic regression analysis examined the relationship between demographic, clinical, and ultrasound variables (dependent variables) and mortality at 3 years (independent variable). Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. To assess the predictive rate of the Gray-Weale score in 3-year mortality, a receiver operating characteristic (ROC) curve, with calculations of the area under the curve and 95% CI, was constructed, and sensitivity and specificity values were calculated.\u003c/p\u003e \u003cp\u003eThe data were analyzed using IBM SPSS Software version 24 (IBM Corp., Armonk, NY, USA). All p values were two-tailed, and p\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered to indicate statistical significance.\u003c/p\u003e"},{"header":"4. RESULTS","content":"\u003cp\u003eA total of 114 patients were recruited. Four patients were excluded because of insufficient transthoracic AA image quality. Two patients who did not complete follow-up were excluded from the analysis. 108 patients completed the three-year study, 50 females and 58 males with an average age of 71.3\u0026plusmn;13.4 years, twenty-one patients (24%) suffered an RS. Twenty-nine patients (26%) died during the three-year follow-up. Demographic, clinical, and laboratory variables of patients without and with RS at 3 years are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea. No statistically significant differences were observed in the use of antiplatelet therapy, anticoagulant therapy, or the absence of treatment between patients with and without atherosclerosis of the aortic arch and carotid arteries. Demographic, clinical, and laboratory variables of patients according to 3-year mortality are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb. Patients who did not experience RS were more likely to present lower systolic blood pressure at enrollment than those with a subsequent stroke (139.2\u0026plusmn;24.2 vs 152.1\u0026plusmn;36.3; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/em\u003e. Patients who experienced fatal outcomes were more likely to present: older age (67.8\u0026plusmn;12.9 vs 80.8 \u0026plusmn;10.1; \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e), higher heart rate (77.5\u0026plusmn;12.3 vs 84.4\u0026plusmn;15.4; 0.017), lower HDL cholesterol levels (45.6\u0026plusmn;14.5 vs 38.6\u0026plusmn;13.7; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.027\u003c/em\u003e), and elevated creatinine (1.1\u0026plusmn;0.4 vs 1.4\u0026plusmn;1.1; \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.041\u003c/em\u003e). Risk factors and comorbidities are presented in supplemental Tables\u0026nbsp;1a and 1b. Smoking history was associated with 3-year mortality (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.021\u003c/em\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Atrial fibrillation (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.032\u003c/em\u003e) and no antiplatelet administered within 48 hours of the onset of stroke symptoms (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.021\u003c/em\u003e) were associated with mortality (Supplemental Tables\u0026nbsp;1b and 2b). Moreover, poor compliance with antiplatelet therapy (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/em\u003e) and statin therapy (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.024\u003c/em\u003e) was also statistically associated with augmented mortality (Supplemental Table\u0026nbsp;2b). The absence of carotid plaque was not statistically associated with a reduction risk of RS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea) but was significantly related to three-year survival (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.008\u003c/em\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Carotid stenosis was not statistically associated with nether RS (Table\u0026nbsp;4a) and mortality (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). AAA alone was not significantly associated with stroke recurrence (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.777\u003c/em\u003e) and mortality (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;1.0\u003c/em\u003e), as shown in Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb. The simultaneous presence of atherosclerotic plaques in both the internal and common carotid arteries was not statistically associated with RS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea) but was significantly associated with mortality (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.004\u003c/em\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The simultaneous presence of atherosclerotic plaques in both carotid and AA was not statistically associated with RS and mortality (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Moreover, the absence of plaques in both carotid and AA was not associated with RS (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Still, it was significantly associated with lower mortality (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.039\u003c/em\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Unsurprisingly, echo-lucent intimal lesions, according to the Gray-Weale classification (Type 1 and 2), considered high-risk plaque (HRP), showed good sensitivity (89.6%) but poor specificity in predicting outcomes at 3 years (AUC\u0026thinsp;=\u0026thinsp;0.63, p\u0026thinsp;=\u0026thinsp;0.0164) (Fig.\u0026nbsp;1). On multinomial regression analysis, age and presence of HRP were statistically correlated with 3-year mortality, albeit the latter in a weakly significant manner (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Association between the stroke characteristics with RS and 3-year mortality are reported in Supplemental Tables\u0026nbsp;3a and 3b. Antiplatelet and anticoagulant therapy\u0026rsquo;s association with the two outcomes is reported in Supplemental Tables\u0026nbsp;4a and 4b.\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\u003ea. Descriptive analysis population: comparison between demographic, clinical, and laboratory variables of patients without and with recurrent stroke at 3 years (mean \u0026plusmn;SD).\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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 \u003cp\u003eVARIABLES\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;87; 80%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRs\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;21; 24%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTOTAL\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e70.3 \u0026plusmn;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75.5\u0026plusmn;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.3\u0026plusmn;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.111\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDAP at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e77.5\u0026plusmn;18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e80.2\u0026plusmn;20.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e78.1\u0026plusmn;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.554\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAP at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e139.2\u0026plusmn;24.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e152.1\u0026plusmn;36.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e141.7\u0026plusmn;27.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.050\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e78.8\u0026plusmn;13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e81.8\u0026plusmn;14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e79.4\u0026plusmn;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.360\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e161.8\u0026plusmn;54.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e163.3\u0026plusmn;43.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e162.1\u0026plusmn;52.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.905\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e44.6\u0026plusmn;14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e40.1\u0026plusmn;13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e43.7\u0026plusmn;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.212\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglyceride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e126.6\u0026plusmn;89.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e117.2\u0026plusmn;37.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e124.8\u0026plusmn;82.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.640\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e96.9\u0026plusmn;45.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e95.9\u0026plusmn;40.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e96.7\u0026plusmn;44.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.935\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10266.9\u0026plusmn;4755.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9402.4\u0026plusmn;2976.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10098.8\u0026plusmn;4466.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.429\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026plusmn;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.2\u0026plusmn;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.2\u0026plusmn;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.873\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e53.3\u0026plusmn;162.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e18.4\u0026plusmn;26.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e46.5\u0026plusmn;147.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.332\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e30.8\u0026plusmn;54.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e31.7\u0026plusmn;40.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e31.0\u0026plusmn;52.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.944\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e173.7\u0026plusmn;1003.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e64.1\u0026plusmn;24.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e152.4\u0026plusmn;900.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.619\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMT mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.215\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCRP: C reactive protein; DAP: diastolic arterial pressure; eGFR: estimated glomerular filtration rate; HR: heart rate; IMT: intima-media thickening; NRS: No recurrent stroke; RS: recurrent stroke; SAP: systolic arterial pressure; WBC: white blood cells.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\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 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eb. Descriptive analysis of the population: comparison between demographic, clinical, and laboratory variables of patients without and with exitus at 3 years (mean \u0026plusmn;SD)\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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 \u003cp\u003eVARIABLES\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO EXITUS\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;79; 80%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEXITUS\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29; 26%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTOTAL\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e67.8\u0026plusmn;12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e80.8\u0026plusmn;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.3\u0026plusmn;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDAP at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e80.9\u0026plusmn;19.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e70.3\u0026plusmn;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e78.1\u0026plusmn;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAP at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e144.1\u003cb\u003e\u0026plusmn;\u003c/b\u003e27.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e135.0\u003cb\u003e\u0026plusmn;\u003c/b\u003e26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e141.7\u0026plusmn;27.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.126\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e77.5\u0026plusmn;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84.5\u0026plusmn;15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e79.4\u0026plusmn;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e162.9\u0026plusmn;51.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e160.1\u0026plusmn;54.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e162.1\u0026plusmn;52.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.806\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e45.6\u0026plusmn;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38.6\u0026plusmn;13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e43.7\u0026plusmn;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglyceride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e127.9\u0026plusmn;84.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e116.5\u0026plusmn;76.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e124.8\u0026plusmn;82.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.527\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL cholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e95.9\u0026plusmn;43.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e98.9\u0026plusmn;47.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e96.7\u0026plusmn;44.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0. 756\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10292.3\u0026plusmn;4457.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9571.7\u0026plusmn;4525.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10098.8\u0026plusmn;4466.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.460\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.1\u0026plusmn;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.4\u0026plusmn;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.2\u0026plusmn;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.041\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e54.5\u0026plusmn;170.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e24.7\u0026plusmn;31.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e46.5\u0026plusmn;147.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.352\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.6\u0026plusmn;52.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e45.7\u0026plusmn;49.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e31.0\u0026plusmn;52.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.076\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e187.3\u0026plusmn;1052.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e57.4\u0026plusmn;25.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e152.4\u0026plusmn;900.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.509\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMT mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026plusmn;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.110\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCRP: C reactive protein; DAP: diastolic arterial pressure; eGFR: estimated glomerular filtration rate; HR: heart rate; IMT: intima-media thickening; SAP: systolic arterial pressure; WBC: white blood cells.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 2a. Ultrasound characteristics and recurrent stroke at 3 years; N\u0026deg; (%)\u003c/strong\u003e. \u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNRS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003en=87)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003en=21)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eARCH AORTIC PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=83)\u003c/p\u003e\n \u003cp\u003eYES (n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e66 (80%)\u003c/p\u003e\n \u003cp\u003e21 (84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (20%)\u003c/p\u003e\n \u003cp\u003e4 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.777\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eABSENCE OF both AORTIC AND CAROTID PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNO (n=95)\u003c/p\u003e\n \u003cp\u003eYes (n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e78 (82%)\u003c/p\u003e\n \u003cp\u003e10 (77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (18%)\u003c/p\u003e\n \u003cp\u003e3 (23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.725\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrey Weale score\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNO PLAQUES (n=16)\u003c/p\u003e\n \u003cp\u003ehypoechoic/predominantly hypoechoic PLAQUES (type 1 and 2) (n=16)\u003c/p\u003e\n \u003cp\u003epredominantly hyperechoic/hyperechoic/\u003c/p\u003e\n \u003cp\u003eCalcific plaques (type 3, 4 and 5) (n=76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (75%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (88%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (25%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (12%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.695\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRESENCE OF BOTH AORTIC AND CAROTID PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=85)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYES (n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;70 (82%)\u003c/p\u003e\n \u003cp\u003e19 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e15 (28%)\u003c/p\u003e\n \u003cp\u003e4 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e0.387\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHEMODYNAMIC STENOSIS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=83)\u003c/p\u003e\n \u003cp\u003ecarotid stenosis (n=23)\u003c/p\u003e\n \u003cp\u003eintracranial stenosis (n=2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67 (81%)\u003c/p\u003e\n \u003cp\u003e18 (78%)\u003c/p\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (19%)\u003c/p\u003e\n \u003cp\u003e5 (22%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.853\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eirregular surface\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eno (n=102)\u003c/p\u003e\n \u003cp\u003eyes (n=6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e82 (80%)\u003c/p\u003e\n \u003cp\u003e5 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (20%)\u003c/p\u003e\n \u003cp\u003e1 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 369px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLAQUE LOCALISATION\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo plaques (n=15)\u003c/p\u003e\n \u003cp\u003eica (n=31)\u003c/p\u003e\n \u003cp\u003ecca (n=27)\u003c/p\u003e\n \u003cp\u003emca (n=1)\u003c/p\u003e\n \u003cp\u003edCl (n=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (73%)\u003c/p\u003e\n \u003cp\u003e24 (77%)\u003c/p\u003e\n \u003cp\u003e23 (85%)\u003c/p\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003cp\u003e28 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (27%)\u003c/p\u003e\n \u003cp\u003e7 (33%)\u003c/p\u003e\n \u003cp\u003e4 (15%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e6 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.807\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCCA: common carotid artery; DCL: double Carotid localization (Common and Internal Carotid; ICA: internal carotid artery; MCA: middle cerebral artery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2b. Ultrasound charateristics and exitus at 3 years; N\u0026deg; (%)\u003c/strong\u003e. \u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNO EXITUS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003en=79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEXITUS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003en=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eARCH AORTIC PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=83)\u003c/p\u003e\n \u003cp\u003eYES (n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61 (73%)\u003c/p\u003e\n \u003cp\u003e18 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (27%)\u003c/p\u003e\n \u003cp\u003e7 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eABSENCE OF both AORTIC AND CAROTID PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNO (n=95)\u003c/p\u003e\n \u003cp\u003eYes (n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e66 (70%)\u003c/p\u003e\n \u003cp\u003e13 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e29 (30%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.039\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGrey Weale score\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNO CAROTID PLAQUES (n=16)\u003c/p\u003e\n \u003cp\u003ehypoechoic/predominantly hypoechoic PLAQUES(n=16)\u003c/p\u003e\n \u003cp\u003epredominantly hyperechoic/hyperechoic/\u003c/p\u003e\n \u003cp\u003eCalcific plaques (n=76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (100%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (81%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (19%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.008\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePRESENCE OF BOTH AORTIC AND CAROTID PLAQUES\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=85)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eYES (n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63 (74%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;16 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (26%)\u003c/p\u003e\n \u003cp\u003e7 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.662\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHEMODYNAMIC STENOSIS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eno (n=83)\u003c/p\u003e\n \u003cp\u003ecarotid stenosis (n=23)\u003c/p\u003e\n \u003cp\u003eintracranial stenosis (n=2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63 (76%)\u003c/p\u003e\n \u003cp\u003e14 (61%)\u003c/p\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (24%)\u003c/p\u003e\n \u003cp\u003e9 (39%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.242\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eirregular surface\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo (n=102)\u003c/p\u003e\n \u003cp\u003eyes (n=6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75 (74%)\u003c/p\u003e\n \u003cp\u003e4 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (26%)\u003c/p\u003e\n \u003cp\u003e2 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.658\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 359px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePLAQUE LOCALIZATION\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo plaques (n=15)\u003c/p\u003e\n \u003cp\u003eica (n=31)\u003c/p\u003e\n \u003cp\u003ecca (n=27)\u003c/p\u003e\n \u003cp\u003emca (n=1)\u003c/p\u003e\n \u003cp\u003edCl (n=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (100%)\u003c/p\u003e\n \u003cp\u003e23 (74%)\u003c/p\u003e\n \u003cp\u003e22 (81%)\u003c/p\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003cp\u003e18 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e8 (26%)\u003c/p\u003e\n \u003cp\u003e5 (19%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e16 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.004\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCCA: common carotid artery; DCL: double Carotid localization (Common and Internal Carotid) ; ICA: internal carotid artery; MCA: middle cerebral artery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eMultinomial regressions for mortality taking into account clinical and ultrasound variables adding age and sex as covariates\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eEXITUS Follow-up at 3 years\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e \u003cp\u003e95% confidence interval for HR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eLower limit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUpper limit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSign.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e1.122\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.053\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.197\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean IMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.985\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e19.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArch aortic plaques\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemodynamic stenosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e1.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e3.438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.943\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrregular surface\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e1.327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e12.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.808\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlaque localisation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e1.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.962\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGRAY-WEALE score 1 or 2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3.702\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.952\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003e14.405\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.059\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e \u003cb\u003ereference: no exitus at 3 years; HR\u0026thinsp;=\u0026thinsp;hazard ratio\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"5. DISCUSSION","content":"\u003cp\u003eThis study demonstrated an association between 3-year all-cause mortality and ultrasonographic characteristics of carotid and AAA in patients with acute IS of all etiologies. Firstly, our data showed that 24% of patients experienced an RS, and 26% died during the three-year follow-up period. Surprisingly, the simultaneous presence of atherosclerotic plaques in the internal or common carotid artery was significantly associated with higher mortality, instead, the simultaneous absence of atherosclerotic plaque in both carotid and AA was strongly related to lower mortality. These results suggest that the extent and characteristics of atherosclerotic disease may be more predictive of overall survival. For years, CDU has been a routine examination performed early in patients with ischemic stroke to evaluate, within 24 hours [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], to detect possible treatable and reversible vascular causes of the stroke and to estimate the patient's cardiovascular risk. The approach to the carotid vessels was preferred because it represented one of the simplest and quickest districts to explore. Furthermore, the carotid arteries\u0026rsquo; size and their course ensure excellent sensitivity and specificity for evaluating atherosclerotic intimal lesions and estimating the patients' cardiovascular risk. Recently, the development of ultrasound equipment and its wider diffusion has led to the possibility of extending the study to the districts upstream and downstream of the carotid and vertebral arteries. The transcranial Doppler and color Doppler study of intravascular circulation has been shown to add valuable diagnostic information capable of modifying the management of patients with acute IS [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similarly, extending the ultrasonological evaluation to the AA allowed for the addition of crucial information for the prognostic stratification of high-risk patients. The AA, due to its anatomical and pressure characteristics, represents a district at high risk of atherosclerotic appositions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The presence of intimal lesions in the AA, as demonstrated by tomographic studies, represents an underestimated cause of embolic stroke of undetermined stroke (ESUS) and RS [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Furthermore, the development of AAA seems to be linked to specific groups of alleles in mice [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], supporting the hypothesis of involvement of distinct pathological processes at different vascular locations. Current guidelines for the prevention of stroke in patients with stroke and transient ischemic attack by the American Heart Association [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] highlighted the importance of AAA detection and suggested intensive lipid management to LDL\u0026thinsp;\u0026lt;\u0026thinsp;70 mg/dl and antiplatelet therapy to prevent RS in these patients. Our study suggests that the co-presence of carotid and AAA could be an expression of a higher cardiovascular risk than the single localizations alone. Therefore, extending the routine study of the carotids to the evaluation of the AA could lead to a more complete and efficient estimation and understanding of the cardiovascular risk of patients with acute IS, as demonstrated by our results in line with the latest evidence. The French Study of Aortic Plaque in Stroke Group showed that the presence in the AA of plaques\u0026thinsp;\u0026gt;\u0026thinsp;4 mm thick was a strong independent predictor of vascular events of all types [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Our data also demonstrate that the absence of carotid and AA atherosclerosis was a strong predictor of survival, confirming the importance of the aortic arch district in estimating patients\u0026rsquo; prognosis.\u003c/p\u003e \u003cp\u003eIn clinical practice, greater importance is given to the presence of atherosclerosis in the internal carotid alone. Interestingly, our data demonstrate instead that the co-presence of intimal lesions in the common carotid is a piece of information that should be taken into account in the estimation of cardiovascular risk and patient prognosis. Unsurprisingly, in our population, the main risk factors for generalized atherosclerosis, such as age, lower HDL cholesterol levels, and elevated creatinine levels, were also significantly associated with mortality. Prospective studies have found an increased RS rate among patients with aortic plaques\u0026thinsp;\u0026ge;\u0026thinsp;4 mm in thickness, particularly with ulceration or mobile components [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] or without plaque calcifications [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our population, AAA alone was not significantly associated with RS, perhaps because of the small sample and because we decided not to subdivide our population according to the thickness of the AAA. This choice was dictated by the desire not to further subdivide the population and reduce the power of statistical analysis. Furthermore, we wanted to demonstrate that the determination of the presence or absence of an atherosclerotic lesion, being a more reproducible data and less influenced by intra and inter-operator variability than the measurement of thickness, can represent a simple tool for the prognostic estimation of patients with IS.\u003c/p\u003e \u003cp\u003eThere are several possible explanations for our mortality data. First, aortic atherosclerosis is known to be strongly associated with arterial stiffness and augmented aortic pulse wave velocity [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. As proposed by Fazekas et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and recently described by Saji et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], elevated pulse wave velocity may contribute to cerebral microcirculatory damage, potentially leading to disrupted vascular dynamics and impaired perivascular flow, which can result in white matter lesions in the brain and glomerular damage in the kidneys. Additionally, an AAA may serve as a marker of widespread atherosclerosis rather than being solely a causative factor in subclinical cerebrovascular and cardiovascular disease. In the only community-based study, the Stroke Prevention: Assessment of Risk in a Community (SPARC) study, researchers found that 86% of patients with a history of TIA, stroke, or endarterectomy had an aortic plaque of any severity, compared to 49% of those without such a history [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, the absence of aortic and carotid lesions could be an expression of lower stiffness and a lower subclinical cardiovascular risk.\u003c/p\u003e \u003cp\u003eOur data appear to be consistent with the results of two other prospective studies with a reasonable follow-up period, one from Ferrari \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and the other from Kazui \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The authors found a major risk of death from stroke or peripheral embolism. Interestingly, in the latter study, lacunar stroke patients were prevalent, suggesting that the investigation and prevention should be directed at all potential causes of future strokes.\u003c/p\u003e \u003cp\u003eAccording to our results, high-risk plaques, as classified by the Gray-Weale system, provide valuable prognostic information for long-term survival but are less predictive of RS. Moreover, echo-lucent intimal lesions classified as HRP according to the Gray-Weale classification (Type 1 and 2) showed good sensitivity (89.6%) but poor specificity in predicting outcomes at three years (AUC\u0026thinsp;=\u0026thinsp;0.63, p\u0026thinsp;=\u0026thinsp;0.0164). Echolucent plaques, particularly the juxta luminal black plaque area, which may represent a thrombus, indicate a higher stroke risk. In a fascinating study [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] conducted on 324 patients with 50\u0026ndash;99% carotid stenosis increasing stenosis, gray scale median (GSM)\u0026thinsp;\u0026le;\u0026thinsp;15 and juxtaluminal black plaque area\u0026thinsp;\u0026ge;\u0026thinsp;8 mm\u003csup\u003e2\u003c/sup\u003e were independent predictors of the presence of hemispheric symptoms and allowed to stratify a high-risk group. In our multivariate analysis, age and the presence of HRP were statistically correlated with three-year mortality. This reinforces the idea that age and specific plaque characteristics, including echogenicity and localization, rather than the presence of stenosis alone, are critical factors in determining long-term outcomes in stroke patients.\u003c/p\u003e \u003cp\u003eInterestingly, while the absence of carotid plaque and AA was not significantly associated with RS risk, it was significantly related to three-year survival, in agreement with recent studies performing CDU. In a prospective study conducted for 34 months on a sample of 541 patients, the authors highlighted that Kaplan-Meier survival estimates have shown the best outcome in patients without carotid plaque [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Furthermore, the carotid plaque score recently proposed to predict the risk of cerebral ischemic events and global cardiovascular risk has shown that a score lower than 3, which includes patients who have no carotid plaque or few small plaques, is associated with the lowest risk profile with reduced mortality [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In 2004, the Rotterdam study demonstrated how non-invasive assessment of extra-coronary atherosclerosis was an excellent predictor of acute myocardial infarction, even fatal. In particular, the co-presence of aortic plaques highlighted by chest X-ray and carotid or lower limb plaques determined a significant increase in risk, proportional also to the severity of the stenosis [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Our study, corroborating these results and proposing the routine use of transthoracic AA evaluation to complement carotid evaluation, keeps pace with technological advances in ultrasound. It is also proposed as a new modus operandi for the ultrasound-based prognostic stratification of patients with IS potentially translatable to all high-risk populations.\u003c/p\u003e"},{"header":"6. LIMITATION OF THE STUDY","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOur study surely presents several limitations. First, the small sample size did not allow us to stratify our population based on aortic arch plaque thickness. Our study aimed not to assess the embolic potential of the plaque itself but to evaluate the contribution of aortic arch assessment in estimating the overall cardiovascular and cerebrovascular risk in these patients. Second, we included all the main subtypes of IS (cardioembolic, associated with large vessel disease, small vessel disease, and cryptogenic). Still, we did not individually evaluate the impact of carotid and AA atherosclerosis for each etiology. At the same time, this allows us to generalize our results to all stroke subtypes and, in the future, to translate the results to other populations at high cardiovascular risk. Third, we did not perform a specific analysis of risk based on therapy (anticoagulant and antiplatelet), but our study was not designed to be a therapeutic trial. Fourth, we did not reevaluate with ultrasound follow-up the evolution of atherosclerotic lesions identified at baseline, but our study aimed to evaluate the combined prognostic power of carotid and aortic arch ultrasound in risk stratification at the time of the first cerebral ischemic event.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"7. CONCLUSIONS","content":"\u003cp\u003eThis study demonstrates that the simultaneous absence of carotid and aortic arch plaques is a significant predictor of survival in patients with acute stroke. Conversely, the presence of high-risk atherosclerotic lesions (Gray-Weale types 1 e 2), along with the simultaneous presence of plaques in the common and internal carotid, is associated with higher mortality. These insights testify to the importance of adapting the screening of cardio and cerebrovascular risk to the new ultrasonographic technological potential through non-invasive ultrasonic evaluation of the aortic arch. Incentivizing the large and routine use of ultrasound evaluation of the carotid and the aortic arch in patients with acute ischemic stroke can guide future studies to stratify better patients for secondary prevention strategies to enhance the quality of care for stroke survivors.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAA: aortic arch; AAA: aortic arch atheromas; CDU: Carotid Duplex Ultrasound; CT: computed tomography; ESUS: embolic stroke of undetermined stroke; HRP: high-risk plaque; IMT: Intimal medial thickening; IS: ischemic stroke; MRI: magnetic resonance imaging; RS: recurrent strokes; TIA: transient ischemic attack; TEE: transesophageal echocardiography.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and images used in the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGiuseppe Miceli\u003c/strong\u003e: Conceptualization, Methodology, project administration, writing-original draft;\u0026nbsp;\u003cstrong\u003eMaria Grazia Basso\u003c/strong\u003e: investigation, data curation; \u003cstrong\u003eAlessandra Casuccio\u003c/strong\u003e: methodology, formal analysis, writing-review and editing; \u003cstrong\u003eChiara Pintus\u003c/strong\u003e: investigation; \u003cstrong\u003eAndrea Roberta Pennacchio\u003c/strong\u003e: investigation, data curation; \u003cstrong\u003eElena Cocciola\u003c/strong\u003e: investigation; \u003cstrong\u003eMariagiovanna Cuffaro\u003c/strong\u003e: investigation; \u003cstrong\u003eMartina Profita\u003c/strong\u003e: investigation; \u003cstrong\u003eGiuliana Rizzo\u003c/strong\u003e: investigation; \u003cstrong\u003eAntonino Tuttolomondo\u003c/strong\u003e:\u0026nbsp;project administration,\u0026nbsp;writing-review and editing, supervision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the Italian Society of Neurosonology and Cerebral Hemodynamic (SINSEC) group for training, education, and general supervision of the research group.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKatan M, Luft A. Global burden of stroke. Semin Neurol 2018;38: 208-1.\u003c/li\u003e\n\u003cli\u003eChanhung Z. Lee, Steven W. Hetts, Interventional Neuroradiology Anesthetic Management, Cottrell \u0026amp; Patel\u0026apos;s Neuroanesthesia, (272-290), (2025).https://doi.org/10.1016/B978-0-323-93273-8.00014-6\u003c/li\u003e\n\u003cli\u003eGray-Weale AC, Graham JC, Burnett JR, Byrne K, Lusby RJ. Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology. J Cardiovasc Surg (Torino). 1988 Nov-Dec;29(6):676-81. PMID: 3062007.\u003c/li\u003e\n\u003cli\u003eNezu T, Hosomi N. Usefulness of Carotid Ultrasonography for Risk Stratification of Cerebral and Cardiovascular Disease. J Atheroscler Thromb. 2020 Oct 1;27(10):1023-1035. doi: 10.5551/jat.RV17044. Epub 2020 Aug 29. PMID: 32863299; PMCID: PMC7585913.\u003c/li\u003e\n\u003cli\u003eFlach C, Muruet W, Wolfe CDA, Bhalla A, Douiri A. 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Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms. \u003cem\u003eJ Vasc Surg\u003c/em\u003e 2010;52:69-76. 10.1016/j.jvs.2010.02.265 \u003c/li\u003e\n\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":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"atherosclerosis, aortic atheroma, carotid plaque, recurrent stroke","lastPublishedDoi":"10.21203/rs.3.rs-6172112/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6172112/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCarotid duplex ultrasound helps to determine the degree of stenosis or occlusion and characterizes plaque composition and vulnerability, which is crucial for stroke risk stratification. Recurrent ischemic stroke poses a significant risk to individuals, with about one-third of stroke survivors experiencing a repeat event within five years. Older age, previous stroke or transient ischemic attack, atrial fibrillation, and large-artery atherosclerosis further increase the risk of recurrent strokes and influence prognosis. Moreover, stroke can result in worse outcomes, including higher morbidity, mortality, and cardiovascular complications in the three years after. This study aims to evaluate the link between ultrasound characteristics of aortic and carotid plaques and the risk of mortality and recurrent stroke among patients with acute ischemic stroke. One hundred-eight patients with first-episode acute ischemic stroke, a mean age of 71.3(13.4) years, underwent carotid Duplex and transthoracic aortic arch ultrasounds. They were followed up every 6 months for three years. The results revealed that while carotid plaques and stenosis were not significantly associated with recurrent stroke, the absence of plaques was related to higher survival rates (p\u0026thinsp;=\u0026thinsp;0.008). Conversely, the simultaneous presence of plaques in both common and internal carotids was associated with increased mortality (p\u0026thinsp;=\u0026thinsp;0.004). Finally, echo-lucent intimal lesions, according to the Gray-Weale classification considered high-risk plaque, showed good sensitivity (89.6%) but poor specificity in predicting outcomes at 3 years (AUC\u0026thinsp;=\u0026thinsp;0.63, p\u0026thinsp;=\u0026thinsp;0.0164). These findings suggest that routine non-invasive ultrasound evaluation of both carotid and aortic arch can be beneficial in stratifying patients for secondary prevention and improving stroke care.\u003c/p\u003e","manuscriptTitle":"Mortality and Recurrence in Acute Ischemic Stroke of All Etiologies According to Ultrasonographic Assessment of Carotid and Aortic Arch Plaques: A Prospective Study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:09:18","doi":"10.21203/rs.3.rs-6172112/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-03-21T13:18:00+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-19T17:26:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-12T12:40:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Internal and Emergency Medicine","date":"2025-03-10T12:24:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2d0d7caf-710e-4593-a8b8-feab7922beef","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T16:06:26+00:00","versionOfRecord":{"articleIdentity":"rs-6172112","link":"https://doi.org/10.1007/s11739-025-04088-x","journal":{"identity":"internal-and-emergency-medicine","isVorOnly":false,"title":"Internal and Emergency Medicine"},"publishedOn":"2025-08-25 15:58:24","publishedOnDateReadable":"August 25th, 2025"},"versionCreatedAt":"2025-03-31 11:09:18","video":"","vorDoi":"10.1007/s11739-025-04088-x","vorDoiUrl":"https://doi.org/10.1007/s11739-025-04088-x","workflowStages":[]},"version":"v1","identity":"rs-6172112","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6172112","identity":"rs-6172112","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}