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Objective: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence., Methods: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration., Results: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ 2 : 12.1 [ p = 0.357] and χ 2 : 21.7 [ p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively., Conclusions: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence., (© 2019 American Academy of Neurology.)

Objective: To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS)., Methods: We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method., Results: Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001)., Conclusions: AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without., Clinicaltrialsgov Identifier: NCT02766205., (© 2019 American Academy of Neurology.)

Objective: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS)., Methods: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death., Results: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively)., Conclusions: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association., (© 2017 American Academy of Neurology.)

Objective: We aimed to investigate the association between leukoaraiosis and long-term risk of stroke recurrence adjusting for clinical scores developed and validated for the prediction of stroke risk, such as CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or TIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category)., Methods: Study population was derived from the Athens Stroke Registry and was categorized in 2 subgroups according to the presence of atrial fibrillation (AF). Cox proportional hazards analysis was performed to assess the independent predictors of stroke recurrence. To investigate whether leukoaraiosis adds to the prognostic accuracy of CHADS2 and CHA2DS2-VASc scores, we used the likelihood ratio test. Overall model assessment was performed with Nagelkerke R(2) and Harrell C statistic. Kaplan-Meier analyses were also performed., Results: Among 1,892 patients, there were 320 (16.9%) with leukoaraiosis and 670 (35.4%) with AF. In the Kaplan-Meier analysis, there was significant difference in cumulative probability of stroke recurrence between patients with and without leukoaraiosis in the non-AF group (p < 0.01), but not in the AF group (p = 0.46). On Cox multivariate analysis, leukoaraiosis was found to be a significant independent predictor of stroke recurrence only in the non-AF group, in the models adjusting for CHADS2 (hazard ratio: 1.86, 95% confidence interval: 1.35-2.56) and CHA2DS2-VASc (hazard ratio: 1.82, 95% confidence interval: 1.32-2.51) scores. Leukoaraiosis was not a predictor of stroke recurrence in the AF group. Leukoaraiosis did not improve the predictive accuracy of the 2 scores, whether in the non-AF group (Harrell C statistic: 0.56 vs 0.59 [p = 0.31] for the model including CHADS2; 0.56 vs 0.59 [p = 0.44] for the model including CHA2DS2-VASc) or the AF group (Harrell C statistic: 0.63 vs 0.62 for the model including CHADS2; 0.64 vs 0.64 for the model including CHA2DS2-VASc)., Conclusions: Leukoaraiosis is an independent predictor of stroke recurrence in non-AF stroke patients. However, leukoaraiosis did not increase the accuracy of the CHADS2 and CHA2DS2-VASc scores to predict stroke recurrence in AF or non-AF stroke patients., (© 2015 American Academy of Neurology.)

Objective: CHADS2 and CHA2DS2-VASc scores are used to assess stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with stroke outcome in non-AF stroke patients., Methods: Consecutive patients with acute first-ever ischemic stroke but without AF were classified into subgroups according to prestroke CHADS2 and CHA2DS2-VASc scores and followed up for 5 years. The end points were death, stroke recurrence, and a composite of major cardiovascular events., Results: Among 1,756 patients (aged 67.2 ± 12.3 years, 68.2% males), there were 258 (14.7%), 617 (35.3%), and 878 (50.0%) patients with low, intermediate, and high CHADS2 score, respectively. The corresponding figures for CHA2DS2-VASc subgroups were 110 (6.3%), 255 (14.5%), and 1,391 (79.2%). There were significant differences between CHADS2 subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 12.3, p = 0.002), and cardiovascular events (log-rank test = 19.4, p < 0.001). Similarly, there were significant differences between CHA2DS2-VASc subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 10.6, p = 0.005), and cardiovascular events (log-rank test = 16.4, p < 0.001). Compared with the low-risk group, patients in intermediate- and high-risk CHADS2 subgroups had higher 5-year mortality (hazard ratio [HR]: 2.22 [95% confidence interval {CI}: 1.78-2.77] and 3.66 [95% CI: 2.38-5.62], respectively), stroke recurrence (HR: 1.74 [95% CI: 1.09-2.79] and 1.71 [95% CI: 1.08-2.71], respectively), and cardiovascular events (HR: 1.78 [95% CI: 1.23-2.57] and 1.86 [95% CI: 1.30-2.67], respectively). Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc subgroup also had higher 5-year mortality (HR: 3.56, 95% CI: 1.89-6.70), stroke recurrence (HR: 2.93, 95% CI: 1.30-6.61), and cardiovascular events (HR: 2.71, 95% CI: 1.49-4.95)., Conclusions: Prestroke CHADS2 and CHA2DS2-VASc scores predict long-term stroke outcomes in non-AF patients with acute ischemic stroke. These scores may provide a simple way of stroke prognostic risk stratification among non-AF stroke patients.

Objective: To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke., Methods: This was a retrospective observational study involving linked hospitalization and death records. The cohort comprised a series of 794 consecutive, first-ever acute ischemic stroke patients from the Athenian Stroke Registry, admitted to the acute stroke unit and the general medicine and neurology ward of our institutions since January 1997 for whom there was available information covering a 10-year follow-up period. Cox proportional hazards model was used to identify risk factors for stroke recurrence and death., Results: The recurrence rate was 16.3% among stroke patients not receiving a statin after hospital discharge compared with 7.5% among those who received statin therapy (p = 0.002). Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio [HR], 0.65, 95% confidence interval [CI] 0.39 to 0.97, p < 0.01). Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event (adjusted HR, 0.43; 95% CI 0.29 to 0.61, p < 0.01)., Conclusions: Prescribing statin therapy upon hospital discharge to patients with first-ever acute stroke lowers the risk of 10-year stroke recurrence and improves survival.