Risk Stratification Of Ischemic Stroke Research Articles

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p<0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p<0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

Circulating levels of potential markers of ischemic stroke in patients with the different forms of atrial fibrillation and chronic heart failure

Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings­ demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events. Keywords: angiostatins, atrial fibrillation, biomarkers, iNOS, ischemic stroke, MMP-9, VEGF

Added Clinical Value of Intraplaque Neovascularization Detection to Color Doppler Ultrasound for Assessing Ischemic Stroke Risk.

Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification. We recruited 360 patients with ≥50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer-Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test. We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666-0.768) and a Hosmer-Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138-0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029-0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617-0.723) increased the C-statistics (p=0.028). Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥50% carotid stenosis.

Carotid plaque score and ischemic stroke risk stratification through a combination of B-mode and contrast-enhanced ultrasound in patients with low and intermediate carotid stenosis.

The occurrence of ischemic stroke (IS) is closely related to the characteristics of carotid plaque (CP). Due to the effect of stroke risk stratification based on B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) that has not been studied in patients with low and intermediate carotid stenosis, we construct and validate a CP score and ischemic stroke risk stratification (ISRS) using a combination of B-mode and CEUS, in order to provide new convenient strategies to stratify these patients to prevent stroke. This retrospective study evaluated 705 patients with low and intermediate carotid stenosis who underwent B-mode and CEUS from November 2021 to April 2023. Qualitative B-mode and CEUS features of carotid plaques were analyzed using a univariable and multivariable logistic regression to construct the CP score. Then, we combined the CP score with Essen stroke risk score (ESRS) to develop ISRS. This study included a total of 705 patients with low and intermediate carotid stenosis, of which 394 were symptomatic patients (with a mean age of 71.03 ± 10.48 years) and 311 were asymptomatic patients (with a mean age of 65.13 ± 10.31 years). Plaque echogenicity, plaque morphology, carotid intima-media thickness in B-mode US and intraplaque neovascularization grading and perfusion pattern in CEUS were significantly associated with IS. The ISRS incorporating these five predictors and ESRS showed good discrimination and calibration in both primary cohort [area under the curve (AUC), 0.91; Hosmer-Lemeshow test, p = 0.903] and validation cohort (AUC, 0.84; Hosmer-Lemeshow test, p = 0.886). We developed an effective and practical tool to identify and stratify patients with low and intermediate carotid stenosis, based on the CP score and ISRS estimation. Our study may provide new insights into managing patients with no indication of surgery.

An interpretable ensemble learning model facilitates early risk stratification of ischemic stroke in intensive care unit: Development and external validation of ICU-ISPM

Ischemic stroke (IS) is a common and severe condition that requires intensive care unit (ICU) admission, with high mortality and variable prognosis. Accurate and reliable predictive tools that enable early risk stratification can facilitate interventions to improve patient outcomes; however, such tools are currently lacking. In this study, we developed and validated novel ensemble learning models based on soft voting and stacking methods to predict in-hospital mortality from IS in the ICU using two public databases: MIMIC-IV and eICU-CRD. Additionally, we identified the key predictors of mortality and developed a user-friendly online prediction tool for clinical use. The soft voting ensemble model, named ICU-ISPM, achieved an AUROC of 0.861 (95% CI: 0.829–0.892) and 0.844 (95% CI: 0.819–0.869) in the internal and external test cohorts, respectively. It significantly outperformed the APACHE scoring system and was more robust than individual models. ICU-ISPM obtained the highest performance compared to other models in similar studies. Using the SHAP method, the model was interpretable, revealing that GCS score, age, and intubation were the most important predictors of mortality. This model also provided a risk stratification system that can effectively distinguish between low-, medium-, and high-risk patients. Therefore, the ICU-ISPM is an accurate, reliable, interpretable, and clinically applicable tool, which is expected to assist clinicians in stratifying IS patients by the risk of mortality and rationally allocating medical resources. Based on ICU-ISPM, an online risk prediction tool was further developed, which was freely available at: http://ispm.idrblab.cn/.

БИОМАРКЕРЫ КРОВИ – ПРЕДИКТОРЫ РАЗВИТИЯ ИШЕМИЧЕСКОГО ИНСУЛЬТА: НОВЫЙ ВЗГЛЯД НА ИЗВЕСТНЫЕ МОЛЕКУЛЫ

Abstract. The number of strokes and deaths from stroke is increasing every year in the world, with ischemic stroke (IS) accounting for about 80% of cases. The purpose of this review is to analyze the results of studies evaluating the significance of measuring various biomarkers in predicting the risk of developing IS. To date, studies are actively exploring the prospects of a number of inflammatory (C-reactive protein, fibrinogen, pro-inflammatory cytokines, etc.), hemodynamic, cardiac, and metabolic biomarkers that can be used to improve the accuracy of IS risk stratification. Currently, it is difficult to isolate the screening biomarker that is the most diagnostically significant for assessing the risk of stroke. Thus, according to a number of studies and meta-analyses, highly sensitive C-reactive protein is a diagnostically significant biomarker of IS. The role of highly sensitive troponin I and natriuretic peptide in diagnosing the risk of IS requires further study. Evaluation of triglyceride-glucose index, apolipoprotein B, apolipoprotein A1, asymmetric dimethylarginine, uric acid seems promising. However, their possible role in the reclassification of asymptomatic patients in addition to the existing scales based on traditional risk factors remains to be elucidated

Dissecting Polygenic Etiology of Ischemic Stroke in the Era of Precision Medicine.

Ischemic stroke (IS), the leading cause of death and disability worldwide, is caused by many modifiable and non-modifiable risk factors. This complex disease is also known for its multiple etiologies with moderate heritability. Polygenic risk scores (PRSs), which have been used to establish a common genetic basis for IS, may contribute to IS risk stratification for disease/outcome prediction and personalized management. Statistical modeling and machine learning algorithms have contributed significantly to this field. For instance, multiple algorithms have been successfully applied to PRS construction and integration of genetic and non-genetic features for outcome prediction to aid in risk stratification for personalized management and prevention measures. PRS derived from variants with effect size estimated based on the summary statistics of a specific subtype shows a stronger association with the matched subtype. The disruption of the extracellular matrix and amyloidosis account for the pathogenesis of cerebral small vessel disease (CSVD). Pathway-specific PRS analyses confirm known and identify novel etiologies related to IS. Some of these specific PRSs (e.g., derived from endothelial cell apoptosis pathway) individually contribute to post-IS mortality and, together with clinical risk factors, better predict post-IS mortality. In this review, we summarize the genetic basis of IS, emphasizing the application of methodologies and algorithms used to construct PRSs and integrate genetics into risk models.

Association of DNA Methylation in Blood Pressure-Related Genes With Ischemic Stroke Risk and Prognosis.

BackgroundA genome-wide association study identified 12 genetic loci influencing blood pressure and implicated a role of DNA methylation. However, the relationship between methylation and ischemic stroke has not yet been clarified. We conducted a large-sample sequencing study to identify blood leukocyte DNA methylations as novel biomarkers for ischemic stroke risk and prognosis based on previously identified genetic loci.MethodsMethylation levels of 17 genes were measured by sequencing in 271 ischemic stroke cases and 323 controls, and the significant associations were validated in another independent sample of 852 cases and 925 controls. The associations between methylation levels and ischemic stroke risk and prognosis were evaluated.ResultsMethylation of AMH, C17orf82, HDAC9, IGFBP3, LRRC10B, PDE3A, PRDM6, SYT7 and TBX2 was significantly associated with ischemic stroke. Compared to participants without any hypomethylated targets, the odds ratio (OR) (95% confidence interval, CI) for those with 9 hypomethylated genes was 1.41 (1.33–1.51) for ischemic stroke. Adding methylation levels of the 9 genes to the basic model of traditional risk factors significantly improved the risk stratification for ischemic stroke. Associations between AMH, HDAC9, IGFBP3, PDE3A and PRDM6 gene methylation and modified Rankin Scale scores were significant after adjustment for covariates. Lower methylation levels of AMH, C17orf82, PRDM6 and TBX2 were significantly associated with increased 3-month mortality. Compared to patients without any hypomethylated targets, the OR (95% CI) for those with 4 hypomethylated targets was 1.12 (1.08–1.15) for 3-month mortality (P = 2.28 × 10−10).ConclusionThe present study identified blood leukocyte DNA methylations as potential factors affecting ischemic stroke risk and prognosis among Han Chinese individuals.

Risk stratification for ischemic stroke and major bleeding in patients without atrial fibrillation – application of CHA2DS2-VASc and HAS-BLED scores

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia. AF-related stroke tends to be more severe, and the mortality rate is higher compared with stroke without AF. Recent cardiac implantable electronic devices (CIEDs) have led to an improvement in the early detection of AF episodes. Previous studies showed that AF episodes detected by CIEDs are associated with ischemic stroke. However, little is known about the relationship between new-onset AF and ischemic stroke events in Japanese patients with CIEDs who have no prior AF and take no anticoagulant therapy. ESC guidelines for the management of AF recommend the use of CHA2DS2-VASc score as class I to predict the risk of ischemic stroke in patients with AF. However, the validity of the CHA2DS2-VASc and HAS-BLED scores to predict ischemic stroke and major bleeding events in patients without AF remains unclear. Objective The purpose of this study was to identify the incidence of ischemic stroke and major bleeding events in CIEDs patients without AF and assess the validity of CHA2DS2-VASc and HAS-BLED scores in this population. Methods We retrospectively analyzed the database of our CIEDs clinic. Every 6 months, CIEDs were checked using remote monitoring system. We examined the characteristics and incidence of ischemic stroke and bleeding events. In addition, we investigated the relationship between CHA2DS2-VASc and HAS-BLED scores and the incidence of these events. Results We enrolled 620 consecutive patients who were followed up at our CIED clinic. We excluded patients who had a history of AF or had received anticoagulant therapies, 348 patients (follow-up period, 65±58 months; age, 70±16 years; male sex; 64%; defibrillator, 55%) were included in this study. The mean CHA2DS2-VASc and HAS-BLED scores were 2.8±1.5 points and 1.7±1.6 points, respectively. During the follow-up, 23 (6.6%) and 12 (3.4%) of 348 patients had ischemic stroke and major bleeding events, respectively. The incidence of ischemic stroke and major bleeding events stratified by the CHA2DS2-VASc and HAS-BLED scores were shown in Figure 1. Conclusion The risk stratification for ischemic stroke and major bleeding using the CHA2DS2-VASc and HAS-BLED scores is valid in patients without AF. Funding Acknowledgement Type of funding sources: None. Figure 1

Prior ischemic strokes are non-inferior for predicting future ischemic strokes than CHA2DS2-VASc score in hemodialysis patients with non-valvular atrial fibrillation

BackgroundWe tested whether CHA2DS2-VASc and/or HAS-BLED scores better predict ischemic stroke and major bleeding, respectively, than their individual components in maintenance hemodialysis (MHD) patients with atrial fibrillation (AF).MethodsA retrospective cohort study of a clinical database containing the medical records of 268 MHD patients with non-valvular AF (167 women, mean age 73.4 ± 10.2 years). During the median follow-up of 21.0 (interquartile range, 5.0–44.0) months, 46 (17.2%) ischemic strokes and 24 (9.0%) major bleeding events were reported.ResultsAlthough CHA2DS2-VASc predicted ischemic stroke risk in the study population (adjusted HR 1.74 with 95% CI 1.23–2.46 for each unit of increase in CHA2DS2-VASc score, and HR of 5.57 with 95% CI 1.88–16.49 for CHA2DS2-VASc score ≥ 6), prior ischemic strokes/transient ischemic attacks (TIAs) were non-inferior in both univariate and multivariate analyses (adjusted HR 8.65 with 95% CI 2.82–26.49). The ROC AUC was larger for the prior ischemic stroke/TIA than for CHA2DS2-VASc. Furthermore, the CHA2DS2-VASc score did not predict future ischemic stroke risks in study participants who did not previously experience ischemic strokes/TIAs (adjusted HR 1.41, 95% CI: 0.84–2.36). The HAS-BLED score and its components did not have predictive abilities in discriminating bleeding risk in the study population.ConclusionsPrevious ischemic strokes are non-inferior for predicting of future ischemic strokes than the complete CHA2DS2-VASc score in MHD patients. CHA2DS2VASc scores are less predictive in MHD patients without histories of CVA/TIA. HAS-BLED scores do not predict major bleeding in MHD patients. These findings should redesign approaches to ischemic stroke risk stratification in MHD patients if future large-scale epidemiological studies confirm them.

Estimate of prevalent ischemic stroke from triglyceride glucose-body mass index in the general population

BackgroundTo investigate the relationship between triglyceride glucose-body mass index (TyG-BMI) and ischemic stroke.MethodsLeveraging two Chinese general population surveys, the Northeast China Rural Cardiovascular Health Study (NCRCHS, N = 11,097) and the National Stroke Screening and Intervention Program in Liaoning (NSSIPL, N = 10,862), we evaluated the relationship between TyG-BMI and ischemic stroke by a restricted cubic spline and multivariate logistic regression after adjusting age, sex, level of education, exercise regularly, current smoking, current drinking, atrial fibrillation, hypertension, coronary artery disease, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The category-free analysis was used to determine whether TyG-BMI enhanced the capacity of estimating ischemic stroke.ResultsA total of 596 and 347 subjects, respectively, from NSSIPL and NCRCHS were survivors of ischemic stroke. In NSSIPL, the relationship between TyG-BMI and ischemic stroke was linear and did not have a threshold or saturation effect according to the results of the restricted cubic spline. The regression analysis indicated that the risk of ischemic stroke increased 20% for per SD increase of TyG-BMI after multivariate adjustment [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.10–1.32]. Compared with those in the lowest tertile, the risk of ischemic stroke in subjects with intermediate and high TyG-BMI was significantly higher [OR (95% CI): 1.39 (1.10–1.74); OR (95% CI) 1.72 (1.37–2.17), respectively]. Category-free analysis indicated that TyG-BMI had a remarkable improvement in the ability to estimate prevalent ischemic stroke [NRI (95% CI): 0.188 (0.105–0.270)]. These abovementioned relationships were confirmed in NCRCHS.ConclusionsThe present study found the robust correlation between TyG-BMI and ischemic stroke, independently of a host of conventional risk factors. Meanwhile, our findings also suggested the potential usefulness of TyG-BMI to improve the risk stratification of ischemic stroke.

LDL Cholesterol and Ischemic Stroke in Patients with Nonvalvular Atrial Fibrillation

BackgroundAtrial fibrillation confers higher risk of ischemic stroke, but the contribution of low-density lipoprotein cholesterol (LDL-C) levels to this risk remains unclear. We examined the association between LDL-C levels and incident stroke in patients with atrial fibrillation treated with direct oral anticoagulants (DOACs). MethodsThis study was conducted using the electronic database of Clalit Health Services in Israel. Included were 21,229 patients with first-time diagnosis of nonvalvular atrial fibrillation treated with DOACs between 2010 and 2017. Patients were categorized into 4 groups according to the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], type 2 diabetes, previous stroke or transient ischemic attack [doubled], vascular disease, age 65-74 years, and sex category) score (1-2, 3-4, 5-6, 7-9). Each group was further stratified to 4 sub-groups according to LDL-C levels (<70, 70-99, 100-130, >130 mg/dL). Ischemic stroke rates were compared among the 4 LDL-C subgroups of each CHA2DS2-VASc category. ResultsDuring 56,467 person-years of follow-up, there were 2481 incidents of ischemic stroke. Higher CHA2DS2-VASc score was associated with significantly increased risk of ischemic stroke (17.5, 26.9, 46.3, 94.9 cases per 1000 person-years, for patients with CHA2DS2-VASc score of 1-2, 3-4, 5-6, and 7-9, respectively; P < .001). However, there was no association between LDL-C levels and incident ischemic stroke within each CHA2DS2-VASc score group, even following a multivariate adjustment. Subanalyses of patients with previous stroke and those treated with statins also failed to show any association between LDL-C levels and incident ischemic stroke. ConclusionsUnlike the general population, LDL-C levels were not associated with ischemic stroke risk among patients with atrial fibrillation treated with DOACs. The findings support the noninclusion of dyslipidemia in ischemic stroke risk stratification of patients with atrial fibrillation.

Abstract WMP48: 3D MR Vessel Wall Imaging Reveals Plaque-Specific Responses to Medical Therapy in Patients With Symptomatic Intracranial Atherosclerotic Disease: Initial Experience

Introduction: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke worldwide and carries a high rate of recurrence. Follow-up of symptomatic ICAD routinely relies on assessment of lumen stenosis. Magnetic resonance vessel wall imaging (MR-VWI) has recently demonstrated the potential to reliably quantify plaque features. This work presents our experience in using serial MR-VWI to quantify the morphological changes of culprit lesions in response to medical therapy in patients with symptomatic ICAD. Methods: Twenty-four patients (4 females; age 46.75±14.05 years) with acute ischemic stroke secondary to ICAD underwent baseline (1-44 days after onset) and follow-up (3-15 months after baseline) 3D whole-brain MR-VWI, which was used to acquire pre- and post-contrast images. Quantitative plaque features, including plaque volume, peak normalized wall index (pNWI), maximum wall thickness, stenosis degree, pre-contrast plaque-wall contrast ratio (CR), and post-contrast plaque enhancement ratio (ER), were derived from both baseline and follow-up MR-VWI scans. Patients with 18-month clinical follow-up were divided into progression and non-progression groups depending on whether major vascular events (stroke, TIA, death) occurred. Results: Seventeen patients were categorized into the non-progression group and 4 into the progression group. Maximum wall thickness (P=0.047), CR (P=0.020) and ER (P=0.012) showed significant decreases in the non-progression group. In the progression group, all 4 patients showed an increase in pNWI, stenosis degree and CR; plaque volume, maximum wall thickness and ER increased in three patients. Typical cases are shown in Figure. Conclusions: Quantitative assessment of lesion-specific responses to medical therapy is clinically feasible with serial MR-VWI. The changes of plaque over time may be useful for ischemic stroke risk stratification with implications for ICAD medical management.

Value of triglyceride-glucose index for the estimation of ischemic stroke risk: Insights from a general population

Background and aimsRecent studies have recognized triglyceride-glucose index (TyG) as a practical surrogate of insulin resistance. Previous studies have demonstrated that insulin resistance contributes to ischemic stroke via multiple mechanisms. Our study aimed to investigate the association between TyG and prevalent ischemic stroke, exploring the value of TyG to optimize the risk stratification of ischemic stroke. Methods and resultsThis cross-sectional study included 10,900 subjects (mean age: 59.95 years, 59.8% females) from rural areas of northeast China between September 2017 to May 2018. TyG was calculated as ln[fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. The prevalence of ischemic stroke was 5.49%. After adjusting for all covariates, each SD increment of TyG caused 22.8% additional risk for ischemic stroke. When dividing TyG into quartiles, the top quartile had a 1.776 times risk for ischemic stroke against the bottom category. Furthermore, smoothing curve fitting demonstrated this association was linear in the whole range of TyG. Finally, AUC revealed an improvement when introducing TyG into clinical risk factors (0.746 vs 0.751, p = 0.029). Consistently, category-free net reclassification index (0.195, 95% CI: 0.112–0.277, P < 0.001) and integrated discrimination index (0.003, 95% CI: 0.001–0.004, P < 0.001) confirmed the improvement by TyG to stratify ischemic stroke risk. ConclusionThe prevent ischemic stroke correlated proportionally with the increment of TyG, implicating the linearity of TyG as an indicator of ischemic stroke. Our findings suggest the potential value of TyG to optimize the risk stratification of ischemic stroke in a general population.

Spotty Calcium on Cervicocerebral Computed Tomography Angiography Associates With Increased Risk of Ischemic Stroke.

Background and Purpose- Cervicocerebral vascular calcification on computed tomography angiography is a known sign of advanced atherosclerosis. However, the clinical significance of calcification pattern remains unclear. In this study, we aimed to investigate the potential association between spotty calcium and acute ischemic stroke. Methods- This study included patients with first-time nonlacunar ischemic stroke (N=50) confirmed by brain magnetic resonance imaging or nonenhanced head computed tomography, as well as control subjects with asymptomatic carotid atherosclerosis (N=50) confirmed by carotid ultrasonography. Subjects in both groups underwent contrast-enhanced cervicocerebral computed tomography angiography within a week after the initial imaging examination. Spotty calcification was evaluated at 11 arterial segments commonly affected by atherosclerosis along the carotid and vertebrobasilar circulation. Statistical analysis was performed comparing the frequency and spatial pattern of spotty calcification between the 2 groups. Results- Spotty calcification in the Stroke group was markedly more prevalent than that in the Control group (total SC count: 8.74±4.96 versus 1.84±1.82, P<0.001). The odds ratio (95% CI) for stroke was 2.49 (1.55-4.00) for spotty calcification at bilateral carotid bifurcation, 1.52 (1.13-2.04) at carotid siphon, and 1.98 (1.45-2.69) at all evaluated locations. A total number of 3 spotty calcifications were determined as the optimal cutoff threshold for increased risk of stroke. Spotty calcium showed significantly greater area under the receiver operating characteristics curve than total calcium volume irrespective of size (0.88 versus 0.77). Within the Stroke group, ipsilateral lateral side showed significantly more spotty calcium than the contralateral side (5.18±3.05 versus 3.56±2.67, P<0.001). Conclusions- Nonlacunar ischemia stroke was associated with markedly increased incidence of spotty calcification with a distinct spatial pattern on cervicocerebral computed tomography compared with subclinical atherosclerosis, suggesting the potential role of spotty calcification for improving the risk stratification for ischemic stroke.

Abstract TP74: Spotty Calcification on Cervicocerebral Computed Tomography Angiography Associates With Increased Risk of Acute Ischemic Stroke

Introduction: Cervicocerebral vascular calcification on cervicocerebral computed tomography angiography is a known sign of advanced atherosclerosis. However, the clinical significance of calcification pattern remains unclear. This study aimed to investigate the potential association between spotty calcium (SC) and acute ischemic stroke. Methods: This study included patients with first-time nonlacunar ischemic stroke (N=50) confirmed by brain MRI or non-enhanced head CT, as well as age and sex-matched control subjects with asymptomatic carotid atherosclerosis (N=43) confirmed by carotid ultrasonography. Subjects in both groups underwent contrast-enhanced cervicocerebral CTA within a week after the initial imaging exam. Spotty calcification was evaluated at eleven arterial segments commonly affected by atherosclerosis along the carotid and vertebrobasilar circulation. Statistical analysis was performed comparing the frequency and spatial pattern of spotty calcification between the two groups. Results: Spotty calcification in the stroke group was markedly more prevalent than that in the control group (total SC count: 8.74±4.96 vs 1.84±1.77, p&lt;0.001). The relative risk for stroke of spotty calcification at bilateral carotid bifurcation, carotid siphon, and all evaluated locations were (95% confidence interval): 2.521 (1.530~4.155), 1.441 (1.073~1.937), and 1.971 (1.434~2.709), respectively. A total number of 3 spotty calcifications was determined as the optimal cutoff threshold for increased risk of stroke. Spotty calcium showed significantly greater area under the receiver-operating characteristics curve (ROC) than that of total calcium irrespective of size (0.88 versus 0.77). Within the stroke group, ipsilateral lateral side showed significantly more spotty calcium than the contralateral side (5.18±3.05 vs. 3.56±2.67, p&lt;0.001). Conclusions: Nonlacunar ischemia stroke was associated with markedly increased incidence of spotty calcification with a distinct spatial pattern on cervicocerebral computed tomography compared with subclinical atherosclerosis, suggesting the potential role of spotty calcification for improving the risk-stratification for ischemic stroke.

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

Plasma homocysteine levels and intracranial plaque characteristics: association and clinical relevance in ischemic stroke

BackgroundElevated plasma homocysteine (Hcy) is an independent risk factor for ischemic stroke. This study aimed to evaluate the association between Hcy levels and intracranial plaque characteristics and to investigate their clinical relevance in ischemic stroke.MethodsNinety-four patients with intracranial atherosclerosis (ICAS) were enrolled. Plasma Hcy levels were measured. Intracranial plaque characteristics including plaque enhancement, stenosis ratio, T2 and T1 hyperintense components were assessed on high-resolution magnetic resonance imaging. Logistic regression model was constructed to analyze the association between high Hcy levels and plaque characteristics, and their synergistic effects to predict the likelihood for ischemic stroke, while adjusting for demographics and traditional atherosclerotic risk factors.ResultsElevated Hcy level was associated with strong plaque enhancement independently of age, sex, serum creatinine levels and other atherosclerotic risk factors ((P < 0.001, OR 6.00, 95% confidence interval [CI] 2.28–15.74). Both strong plaque enhancement (P = 0.026, OR 5.63, 95% CI 1.23–25.81) and high Hcy level (P = 0.018, OR 6.20, 95% CI 1.36–28.26) were correlated with acute ischemic stroke. The combination of them strengthened the ability to stratify the likelihood for ischemic stroke, with an improved area under the receiver operating characteristic curve (AUC) of 0.871, significantly higher than that of strong plaque enhancement (0.755) and high Hcy level (0.715) alone (P < 0.05 for both).ConclusionsHigh Hcy level appears to have association with intracranial strong plaque enhancement. The combined assessment of plasma Hcy levels and plaque enhancement may improve ischemic stroke risk stratification.

The association of high D-dimer level with high risk of ischemic stroke in nonvalvular atrial fibrillation patients: A retrospective study.

This study aimed to explore the relationship of D-dimer level with the risk stratification of ischemic stroke, and determine whether high D-dimer levels could be used as a risk factor of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF).This single-center, retrospective study recruited NVAF patients who did not undergo anticoagulant therapy. These patients were divided into 2 groups: ischemic stroke group and no-stroke group. The medical records of each patient were reviewed, demographic and clinical analyses were performed, and the laboratory results were summarized.A total of 323 eligible in-patients with NVAF, who did not receive anticoagulant therapy, were recruited (206 male and 117 female patients, median age was 75.18 ± 10.46 years old). Among these patients, 78 patients suffered from acute ischemic stroke. D-dimer level increased with age, and was positively correlated with the risk stratification of stroke, CHADS2 score (rs = 0.441, P < .001), and CHA2DS2-VASC score (rs = 0.412, P < .001), even after adjustment for age and gender (rs = 0.422, P < .001). The difference in baseline D-dimer level between these 2 groups was not statistically significant (0.70 vs 0.66 mg/L, P = .330), but this significantly increased when patients suffered from stroke (1.34 vs 0.70 mg/L, P < .001). The D-dimer level after stroke (≥6 months) was also higher than the baseline (1.16 vs 0.68 mg/L, P = .514) in 6 months, and this level nearly returned to baseline level after one year (0.69 vs 0.68 mg/L, P = .158). However, logistic regression revealed that only the D-dimer level at stroke onset and OMI were independent risk factors for ischemic stroke (P < .001), while the increase from baseline D-dimer levels was not an independent risk factor (P = .125).D-dimer level is positively correlated with the risk stratification of ischemic stroke, but has no predictive value on the occurrence of ischemic stroke in patients with NVAF.

Stroke prediction with CHA2DS2-VASc score in patients with mesenteric ischemia without atrial fibrillation-insights from a nationwide cohort

BackgroundThe current study sought to evaluate the accuracy of CHA2DS2-VASc score for ischemic stroke prediction in patients with mesenteric ischemia without atrial fibrillation (AF). MethodsThe study participants included patients aged ≥18years with a new diagnosis of mesenteric ischemia during hospitalization between January 1, 2000 and December 31, 2011. Individuals with atrial fibrillation (AF) or atrial flutter during the study period were excluded. The study participants were followed up until the ischemic stroke appeared or they were censored due to withdrawal from this program, mortality, or the end of the study period, whichever came first. Cox proportional hazards regression models were applied for ischemic stroke risk stratification in the study participants by CHA2DS2-VASc score. The c-statistic based on the receiver operating characteristic (ROC) analysis was applied to investigate the accuracy of CHA2DS2-VASc score for ischemic stroke risk discrimination. ResultsA total of 24039 study participants were enrolled. Ischemic stroke incidence increased from 1.54% in CHA2DS2-VASc score of 0 to 9.23% in CHA2DS2-VASc score of 6 or more. Moreover, the Kaplan–Meier curve with a log rank test demonstrated that patients with a higher CHA2DS2-VASc score were associated with an increased cumulative incidence rate of ischemic stroke during the follow-up period (p<0.001). The discriminatory performance of the CHA2DS2-VASc score resulted in C-statistics of 0.65(95% CI=0.63–0.66) for predicting ischemic stroke risk among patients with mesenteric ischemia without AF. ConclusionsA higher CHA2DS2-VASc score is demonstrated to be associated with an increased risk of ischemic stroke among patients with mesenteric ischemia without comorbid AF.