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BackgroundEmbolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial.MethodsThe validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods.ResultsOf the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1).ConclusionsThis external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS.Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.

Background and purpose The association between intracranial artery calcification (IAC) and the risk of ischemic stroke occurrence or poor prognosis had not yet been fully understood. In this study, we conducted a meta-analysis of existing studies aimed to assess whether IAC can be used to predict future ischemic stroke and post-stroke mortality. Methods Medline, Cochrane, Web of Science and Google Scholar databases were searched up to June 30, 2022. Studies were included if they reported risk ratio (RR) or odds ratios (OR) and corresponding 95% confidence intervals (CI) of stroke concerning the presence of IAC. Random or fixed effects model meta-analyses were performed. Meta-analysis was conducted by using Stata version 16.0. Results Twelve studies involving 9346 participants were included. Compared with those without IAC, patients with IAC had a higher risk of stroke occurrence (adjusted OR 1.62, 95% CI 1.18–2.23, P  = 0.001) and stroke recurrence (adjusted OR 1.77, 95% CI 1.25–2.51, P  = 0.003). However, we did not find a significant correlation between IAC and post-stroke mortality (pooled OR 1.12, 95% CI 0.80–1.56, P  = 0.504). Conclusions Our meta-analysis demonstrated that the presence of IAC was identified as an independent risk factor for ischemic stroke occurrence and recurrence but is not a predictor of post-stroke mortality.

Objectives To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD). Methods This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan–Meier survival analysis. Results Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34–7.42) per 10% increase in plaque burden and 2.17 (1.27–3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629–0.822) for plaque burden, 0.692 (95% CI 0.593–0.792) for enhancement ratio, and only 0.595 (95% CI 0.492–0.699) for the Essen stroke risk score. The Kaplan–Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p  < 0.001). Conclusion Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence. Clinical relevance statement In patients with symptomatic ICAD, the results of this high-resolution magnetic resonance vessel wall imaging study have potential implications for optimal management of intracranial plaques and secondary prevention of stroke recurrence based on plaque burden and enhancement ratio. Key Points • Identification of intracranial plaque characteristics responsible for stroke recurrence is essential to preventing stroke recurrence in patients with symptomatic intracranial atherosclerotic disease. • Higher plaque burden and enhancement ratio are independent risk factors for stroke recurrence. • Plaque burden and enhancement ratio are valuable imaging markers in the prediction and stratification of the risk of stroke recurrence.

Left atrial strain (LAS) has been widely studied as a predictor of atrial fibrillation (AF) after cryptogenic stroke (CS). However, the evidence about its prognostic role in terms of stroke recurrence and death in this setting remains scarce. A total of 92 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography, including LAS was performed during admission. The primary outcome measure was the composite of stroke recurrence or death. The mean age was 77.5 ± 7.7, and 58% of patients were female. After a median follow up of 28 months, the primary outcome measure occurred in 15 patients (16%). The primary outcome was more frequent in patients with diabetes (53% vs 21%, p = 0.02), chronic kidney disease (33% vs 10%, p = 0.034), and a history of heart failure (13% vs 0%, p = 0.025). LAS reservoir (LASr) and LAS conduit (LAScd) were lower in patients developing the primary outcome (21% ± 7% vs 28.8% ± 11%, p = 0.017 and 7.7% ± 3.9% vs 13.7% ± 7%, p = 0.007, respectively). On multivariate analysis, LASr (hazard ratio 0.9, 95% confidence interval 0.85 to 0.99, p = 0.048) and diabetes (hazard ratio 3.3, 95% confidence interval 1.03 to 10.4, p = 0.045) were associated with stroke recurrence or all-cause death after CS. On the log-rank test (using the discriminatory cut-off value of LASr <23%), LASr (p = 0.009) was associated with higher risk of the primary outcome. In conclusion, lower values of the LAS reservoir were associated with a higher risk of stroke recurrence or death after CS. LAS may identify patients at higher risk of thromboembolism and stress conditions.

Background The high incidence of stroke recurrence necessitates effective post-stroke care. This study investigates the effectiveness of a case management-based post-stroke care program in patients with acute stroke and TIA. Methods In this prospective cohort study, patients with TIA, ischemic stroke or intracerebral hemorrhage were enrolled into a 12-month case management-based program (SOS-Care) along with conventional care. Control patients received only conventional care. The program included home and phone consultations by case managers, focusing on education, medical and social needs and guideline-based secondary prevention. The primary outcome was the composite of stroke recurrence and vascular death after 12 months. Secondary outcomes included vascular risk factor control at 12 months. Results From 11/2011 to 12/2020, 1109 patients (17.9% TIA, 77.5% ischemic stroke, 4.6% intracerebral hemorrhage) were enrolled. After 85 (7.7%) dropouts, 925 SOS-Care patients remained for comparative analysis with 99 controls. Baseline characteristics were similar, except for fewer males and less frequent history of dyslipidemia in post-stroke care. At 12 months, post-stroke care was associated with a reduction in the composite endpoint compared to controls (4.9 vs. 14.1%; HR 0.30, 95% CI 0.16–0.56, p  < 0.001), with consistent results in ischemic stroke patients alone (HR 0.32, 95% CI 0.17–0.61, p  < 0.001). Post-stroke care more frequently achieved treatment goals for hypertension, dyslipidemia, diabetes, BMI and adherence to secondary prevention medication ( p  < 0.05). Conclusions Case management-based post-stroke care may effectively mitigate the risk of vascular events in unselected stroke patients. These findings could guide future randomized trials investigating the efficacy of case management-based models in post-stroke care.

Backgroud and purpose Triglyceride-glucose (TyG) index has been considered a surrogate marker of insulin resistance. We investigated the association between TyG index and stroke recurrence and compared the effectiveness of TyG index with homeostasis model assessment of insulin resistance (HOMA-IR) in predicting stroke recurrence and death in nondiabetic acute ischemic stroke patients. Methods Nondiabetic acute ischemic stroke patients from the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry were included. TyG index was performed and classified into four groups by quartiles. The outcomes were stroke recurrence and death within 1 year. The association between TyG index and the risk of stroke recurrence and death were analyzed by Cox regression models. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prediction of TyG index and HOMA-IR for stroke recurrence and death. Delong test was used for comparing the differences between area under the curve (AUC) of TyG index and HOMA-IR. Results Among the 1226 patients included, the median (interquartile range) of TyG index was 5.8 (5.5–6.2). Both the third and fourth quartiles of TyG index were associated with an increased risk of stroke recurrence (adjusted hazard ratio 2.04, 95% confidence interval 1.26–3.31; adjusted hazard ratio 1.86, 95% confidence interval 1.13–3.06). Patients with fourth quartiles of TyG index were associated with a higher mortality risk (adjusted hazard ratio, 2.91; 95% confidence interval, 1.62–2.53). Regarding stroke recurrence within 1 year, the AUC (95% confidence interval) of the ROC curve for the TyG index was similar to that of the HOMA-IR[0.56 (0.52–0.61) vs 0.57 (0.52–0.61); P  = 0.93]. Regarding death within 1 year, the AUCs (95% confidence interval) of the ROC curve for the TyG index and HOMA-IR were 0.55 (0.50–0.61) and 0.59 (0.53–0.64), respectively ( P  = 0.32). Conclusions Elevated TyG index was associated with an increased risk of stroke recurrence and death. However, neither of TyG nor HOMA-IR can be a qualified predictor of stroke recurrence and death in nondiabetic acute ischemic stroke patients.

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16–55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60 % men), median age was 46 (IQR 39–51) years and median NIHSS on admission 3 (IQR 1–8). Modifiable vascular risk factors were found in 73 %. Stroke aetiology was mostly cardioembolism (32 %) and of other defined origin (24 %), including cervicocerebral artery dissection (17 %). Fabry disease was diagnosed in 2 patients (0.3 %). Aetiology remained unknown in 20 %. Outcome at 3 months was favourable (mRS 0–1) in 61 % and fatal in 2.9 %. Stroke severity ( p  < 0.001) and diabetes mellitus ( p  = 0.023) predicted unfavourable outcome. Stroke recurrence rate at 3 months was 2.7 %. Previous stroke or TIA predicted recurrent cerebrovascular events ( p  = 0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.

Background Risk stratification based on intracranial plaque characteristics is crucial for patients with intracranial atherosclerosis (ICAS). Nonetheless, there remains a significant deficit of validated imaging markers capable of predicting recurrent strokes. Consequently, we conducted a systematic review and meta-analysis to investigate the prognostic significance of high-risk plaque characteristics (HPCs) in relation to recurrent stroke. Methods The systematic review was registered in PROSPERO (CRD420245820945). We systematically searched PubMed, Ovid Medline, and Web of Science for studies evaluating the association between HPCs and risk of stroke recurrence. Data were aggregated and pooled using a random-effects meta-analysis. Heterogenicity and publication bias were assessed, with subgroup and sensitivity analyses performed where appropriate. Results Eighteen studies, comprising 13 prospective and 5 retrospective, involving a total of 4967 patients (3594 symptomatic, and 1373 asymptomatic), were included in the analysis. Among symptomatic patients, those with HPCs exhibited a higher incidence of stroke recurrence compared to those without HPCs (adjusted HR, 3.90 ([95% CI, 2.15–7.08]). ICAS patients with baseline plaque enhancement (adjusted HR, 5.20 [95% CI, 3.12–8.66]), calcification (adjusted HR, 2.92 [95% CI, 1.32–6.45]), high plaque steepness (adjusted HR, 110.27 [95% CI, 4.75–2559.74]), and progression in plaque burden (adjusted HR, 6.29 [95% CI, 1.62–24.45]) were identified as being at an increased risk of stroke recurrence. Subgroup analyses revealed that traditional cerebrovascular risk factors, including increasing age, hypertension, diabetes mellitus, and smoking, further elevated the risk of HPC-related stroke recurrence in ICAS patients. Conclusion The identification of HPCs confers independent prognostic value for the prediction of stroke recurrence in ICAS patients, which could be instrumental for patients risk stratification.

Background and purpose Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. Methods Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. Results The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27–0.88; and RD 1.39; CI − 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23–0.80; and RD 9.05; CI 2.78–15.32). Conclusions In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention.

BACKGROUND: Cardiovascular diseases, hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation are the most common modifiable risk factors for recurrent ischemic stroke. In this study, we aimed to find the risk factors associated with more than two recurrent ischemic strokes after the first-ever stroke. METHODS: We collected the ischemic stroke patients in our stroke registry data bank, and the eligible patients were followed for recurrent ischemic stroke after 2008. Our study consisted of 927 patients who were followed up for 9 years after the first-ever stroke. RESULTS: We found that 185 (20%) patients had a recurrent ischemic stroke, and another 32 (3.5%) patients had more than one recurrence after the first-ever ischemic stroke. The mean time for the first stroke recurrence was 1 year, and the mean time for the multiple stroke recurrences was 3 years. Significant risk factors for multiple recurrences were congestive heart disease (P < 0.015) and diabetes mellitus (P < 0.006). CONCLUSIONS: We concluded that even with the appropriate treatments, patients with congestive heart disease and diabetes mellitus have a higher rate of multiple recurrences for ischemic stroke after the first-ever ischemic stroke, indicating that more attention should be paid to this issue.