Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea.

BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Post-Stroke Depressive Symptoms: Varying Responses to Escitalopram by Individual Symptoms and Lesion Location.

OBJECTIVE: The efficacy of antidepressants in post-stroke depressive symptoms (PSD) varies. We aimed to examine whether the effect of escitalopram on PSD differs according to individual depressive symptoms and stroke lesion location. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram on depression in acute stroke patients (237 with placebo, 241 with escitalopram). Depressive symptoms were evaluated with the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Changes in MADRS and individual item scores at 12 weeks were compared between the treatment groups and among the stroke lesion location groups. Stroke lesion locations were grouped according to the anatomical distribution of serotonin fibers that originate from the midbrain/pons and spread to the forebrain via subcortical structures: "Midbrain-Pons," "Frontal-Subcortical," and "Others." Least-squares means were calculated to demonstrate the independent effect of lesion location. RESULTS: Total MADRS scores decreased more significantly in the escitalopram than in the placebo group, while a significant effect of escitalopram was observed in only 3 items: apparent sadness, reported sadness, pessimistic thoughts. In the lesion location analyses, escitalopram users in the Frontal-Subcortical group showed significant improvement in total MADRS scores (placebo [n = 130] vs. escitalopram [n = 148], least-square mean [95% CI]: -2.3 [-3.5 to -0.2] vs. -4.5 [-5.5 to -3.4], p = .005), while those in the Midbrain-Pons and Others groups did not. CONCLUSIONS: The effect of escitalopram on PSD may be more prominent in patients with particular depressive symptoms and stroke lesion locations, suggesting the need for tailored treatment strategies.

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

BACKGROUND: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex. RESULTS: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009). CONCLUSION: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed.

Serotonin transporter gene polymorphisms may be associated with poststroke neurological recovery after escitalopram use.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery. METHODS: This was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke. Patients with no/minimal disability initially (modified Rankin Scale (mRS) 0-1) were excluded. Of the participants, 301 underwent genetic studies of the STin2 (a variable number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes) and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of SERT. We explored whether neurological function (National Institutes of Health Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT polymorphisms within each treatment arm (escitalopram and placebo). RESULTS: Among the escitalopram users (n=159), neurological function in subjects with STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2 12/10 independently predicted a good clinical outcome (mRS 0-1) (OR 2.99, 95% CI 1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not associated with neurological recovery in any treatment group. CONCLUSION: STin2 VNTR polymorphisms may be associated with poststroke neurological recovery after SSRI therapy. Further studies are needed to identify the role of serotonin in neurological recovery after stroke.

Use of microcatheters for suction thrombectomy of acute distal occlusions.

We report our initial experience of using a microcatheter for contact aspiration of acute distal occlusions for recanalization. Endovascular technique and a case using Excelsior XT-27 microcatheter are presented. After manual suction within distal middle cerebral artery segments using a 50-ml syringe, instant and complete recanalization was obtained. Microcatheter suction thrombectomy using a 50-ml syringe can be considered a feasible treatment option for acute distal small artery occlusions.

Medication Adherence of Statin Users after Acute Ischemic Stroke.

Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients' awareness of hyperlipidemia (OR 1.62; 95% CI 1.07-2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19-2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06-2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40-0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88-0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.

The Effect of Inter-Departmental Stroke Meetings on Rehabilitation in a Comprehensive Cerebrovascular Center.

BACKGROUND: Stroke is the number one cause of adulthood disability in Korea. Rehabilitation after stroke can minimize functional disability, enhance recovery toward independence, and optimize community reintegration. The inter-departmental stroke meeting (IDSM) is a potential method to improve rehabilitation outcomes in patients with stroke. We aimed to analyze the effect of IDSM on rehabilitation after acute ischemic stroke management. METHODS: Medical records of 753 patients with acute ischemic stroke admitted to the neurology department of our medical center between January and December 2014 were reviewed retrospectively. In May 2014, weekly IDSMs were initiated. All physicians responsible for the patient's care reviewed patient treatment, methods of secondary prevention, and future rehabilitation plans. RESULTS: The transfer rate significantly increased after initiation of IDSM (phase 2, 3) and the length of stay (LOS) before transfer to the rehabilitation department decreased significantly from 9.68 ± 8.50 days to 5.75 ± 2.12 days. There was a reduction in the total LOS from 52 ± 28.57 days to 35 ± 27.21 days after IDSMs were introduced. In non-transferred patients also, the total LOS reduced significantly. The transfer rate increased significantly and the LOS before transfer to the rehabilitation department decreased significantly after implementation of IDSM in a subgroup of patients with moderate to severe stroke. CONCLUSION: The introduction of IDSM was significantly correlated with improvements in transfer rates and reduction of LOS in hospital. This finding shows that IDSMs are an important intervention to improve therapeutic progress and outcomes for patients with stroke.

Brachial-ankle PWV for predicting clinical outcomes in patients with acute stroke.

BACKGROUND: Although brachial-ankle pulse wave velocity (baPWV) is well-known for predicting the cardiovascular mortality and morbidity, its anticipated value is not demonstrated well concerning acute stroke. METHODS: Total 1557 patients with acute stroke who performed baPWV were enrolled. We evaluated the prognostic value of baPWV predicting all-cause death and vascular death in patients with acute stroke Results: Highest quartile of baPWV was ≥23.64 m/s. All-caused deaths (including vascular death; 71) were 109 patients during follow-up periods (median 905 days). Multivariate Cox regression analysis revealed that patients with the highest quartile of baPWV had higher risk for vascular death when they are compared with patients with all other three quartiles of baPWV (Hazard ratio with 95% confidence interval [CI] 1.879 [1.022-3.456], p = .042 for vascular death). CONCLUSION: High baPWV was a strong prognostic value of vascular death in patients with acute stroke.

Prognostic Relationships between Microbleed, Lacunar Infarction, White Matter Lesion, and Renal Dysfunction in Acute Ischemic Stroke Survivors.

BACKGROUND: It is well known that renal dysfunction and cerebral small-vessel disease (SVD), including microbleed, lacunar infarction, and white matter lesion (WML), are associated with poor prognosis after ischemic stroke. However, the prognostic relationship between renal dysfunction and SVD has not been well evaluated in acute ischemic stroke survivors. Therefore, in this study, we evaluated the prognostic relationships between estimated glomerular filtration rate (eGFR) and cerebral SVD after acute ischemic stroke. METHODS: We retrospectively reviewed the clinical and radiological data of acute ischemic stroke survivors with decreased eGFR (<60 mL/min/1.73 m2, n = 128) and controls (eGFR ≥60 mL/min/1.73 m2, n = 128). The presence of SVD was evaluated according to magnetic resonance imaging performed on admission. Mortality data were obtained from medical chart reviews and telephone interviews. RESULTS: Patients with silent lacunar infarction, WML, or microbleed had lower eGFR than patients without such lesions (60.4 ± 34.8 versus 87.5 ± 28.4 mL/min/1.73 m2, 60.5 ± 37.1 versus 73.9 ± 33.3 mL/min/1.73 m2, and 57.6 ± 33.3 versus 73.9 ± 32.9 mL/min/1.73 m2, respectively). In addition, the multivariate adjusted odds ratio for the presence of SVD increased inversely with eGFR. Three-year survival was lower in patients with renal dysfunction and each type of SVD. The presence of WML was an independent risk factor for cardiovascular death. CONCLUSIONS: Renal impairment was associated with the presence of SVD in acute ischemic stroke survivors. Both renal impairment and the presence of SVD were predictors of poor poststroke survival.

Establishment of government-initiated comprehensive stroke centers for acute ischemic stroke management in South Korea.

BACKGROUND AND PURPOSE: In 2008, the Ministry of Health and Welfare of South Korea initiated the Regional Comprehensive Stroke Center (CSC) program to decrease the incidence and mortality of stroke nationwide. We evaluated the performance of acute ischemic stroke management after the Regional CSC program was introduced. METHODS: The Ministry of Health and Welfare established 9 Regional CSCs in different provinces from 2008 to 2010. All Regional CSCs have been able to execute the critical processes independently for stroke management since 2011. The Ministry of Health and Welfare was responsible for program development and financial support, the Regional CSC for program execution, and the Korea Centers for Disease Control and Prevention for auditing the execution. We analyzed prospectively collected data on the required indices from 2011 and repeated the analysis the following year for comparison. RESULTS: After the Regional CSCs were established, the first brain image was taken within 1 hour from arrival at the emergency room for all patients with stroke; the length of hospital stay decreased from 14 to 12 days; for the rapid execution of thrombolysis, the first brain image was taken within 12 minutes; intravenous and intra-arterial thrombolysis were started within 40 and 110 minutes, respectively, after emergency room arrival; and the hospital stay of thrombolytic patients decreased from 19 to 15 days. CONCLUSIONS: The Regional CSC program has improved the performance of acute stroke management in South Korea and can be used as a model for rapidly improving stroke management.

Reverse dipper and high night-time heart rate in acute stage of cerebral infarction are associated with increased mortality.

BACKGROUND: Reverse dipper, blood pressure (BP) rises during night-time, is a risk factor of increased cardiovascular events in hypertensive patients. However, we have little information whether reverse dipper in acute stage of cerebral infarction (CI) affects on the recurrence and mortality. We studied to assess the relationship between reverse dipper and adverse clinical outcomes in the acute stage of CI. METHODS: We screened and enrolled consecutive patients with acute CI with ambulatory blood pressure monitoring (ABPM) within 2 weeks after admission from August 2001 to July 2005. According to systolic blood pressure (SBP) dropping pattern during night-time compared with daytime, we classified into extreme dipper (≥20%), dipper (≥10%, <20%), nondipper (≥0%, <10%), and reverse dipper (BP rises during night-time). RESULTS: We analyzed 426 patients (72 ± 13 years old, 255 men) and checked recurrence of CI or all-cause mortality for further 7.6 ± 3.1 years for checking of recurrence or all-cause mortality. Of 426 patients, 202 patients were nondippers (47%), 134 were reverse dippers (32%), 80 were dippers (19%), and 10 were extreme dippers (2%). During the follow-up period, 89 patients (21%) had recurrence of CI. After multivariate analysis, daytime SBP (hazard ratio = 1.014, P = .018) was the significant predictor of recurrence. There were 141 deaths (33%) in our study cohort. Multivariate analysis showed that age (hazard ratio = 1.106, P < .001), nocturnal mean heart rate (hazard ratio = 1.023, P = .004), and reverse dipper (hazard ratio = 1. 676, P = .007) were statistically significant. CONCLUSIONS: Reverse dipper and high night-time heart rate in the acute stage of CI were associated with total mortality during long-term follow-up. These findings suggest the clinical utility of ABPM in acute stage of CI.

Predictive factors for early clinical improvement after intra-arterial thrombolytic therapy in acute ischemic stroke.

BACKGROUND: In acute ischemic stroke, the speed of improvement after intra-arterial thrombolytic therapy (IAT)-mediated recanalization varies. This study aimed to identify clinical and radiological variables that are predictive of early improvement (EI) after IAT in acute ischemic stroke. METHODS: This single-center retrospective cohort study included 141 consecutive patients who underwent IAT for terminal internal carotid and/or middle cerebral artery (MCA) occlusions. EI was defined as a National Institutes of Health Stroke Scale (NIHSS) score less than 3 or NIHSS score improvement of 8 points or more within 72 hours of IAT. The EI and non-EI groups were compared in terms of clinical and radiological findings before and after IAT. RESULTS: Forty-nine patients showed EI (34.8%). Multivariate analysis revealed that atrial fibrillation (odds ratio [OR] .35, 95% confidence interval [CI] .14-.89, P = .028) and hyperdense MCA sign (OR .39, CI .15-.97, P = .042) were related with lack of EI. The independent EI predictors were less extensive parenchymal lesion on baseline computed tomography (OR 4.92, CI 1.74-13.9, P = .003), intermediate to good collaterals (OR 3.28, CI 1.16-9.31, P = .026), and recanalization within 6 hours of symptom onset (OR 5.2, CI 1.81-14.94, P = .002). EI associated with favorable outcomes (modified Rankin scale score 0-2) at discharge (88% versus 7%; P < .001) and 3 months after discharge (92% versus 18%; P < .001). CONCLUSIONS: The clinical and radiological variables maybe useful for predicting EI and favorable long-term outcomes after IAT.

NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders.

Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body's defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks. CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Intracranial hemodynamic stabilization patterns after stenting of severe stenosis in the proximal internal carotid artery.

PURPOSE: To evaluate intracranial hemodynamic stabilization patterns after carotid artery stenting (CAS) in patients having variable collateral developments before CAS. METHODS: The hemodynamic and angiographic data of 62 patients (58 men; mean age 68.0±8.4 years) who underwent CAS for unilateral proximal internal carotid artery stenosis were analyzed. The patients had transcranial Doppler examinations before and at 1 and 90 days after CAS. Patients were classified according to pre-CAS mean blood flow velocity (MBFV) of the ipsilateral middle cerebral artery (MCA): low (<30 cm/s; n=17), normal (30 to 48 cm/s; n=26), or high (>48 cm/s; n=19). The collaterals from contralateral anterior and/or posterior circulations prior to CAS, the stabilization pattern of MBFV, and the pulsatility index (PI) after CAS were compared across the 3 groups. RESULTS: The presence of collaterals was lowest in the low MBFV group (17.6% of patients) than in the normal (38.5%) or high (68.4%) MBFV groups (p=0.008). The low MBFV group exhibited an increase in MBFV and PI in the ipsilateral MCA at 1 and 90 days after CAS (p<0.05). By contrast, the high MBFV group exhibited a decrease in MBFV and no change in PI in the ipsilateral MCA up to 90 days after CAS (p<0.05). The normal MBFV group showed an increase in MBFV at post-CAS day 1 but a subsequent decrease at 90 days and an increase in PI in the ipsilateral MCA at 1 and 90 days post-CAS (p<0.05). CONCLUSION: The pattern of post-CAS intracranial hemodynamic stabilization differs according to the pre-CAS MBFV in the ipsilateral MCA.

Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells.

BACKGROUND: Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be used as an epigenetic tool to evaluate the impact of aging and the environment on atherosclerosis development. However, gene-specific methylation changes are currently inadequate epigenetic markers for predicting atherosclerosis and cardiovascular disease pathogenesis. RESULTS: We profiled and validated changes in gene-specific promoter methylation associated with atherosclerosis using stenosis radiophenotypes of cranial vessels and blood inflammatory cells rather than direct sampling of atherosclerotic plaques. First, we profiled gene-specific promoter methylation changes using digital restriction enzyme analysis of methylation (DREAM) sequencing in peripheral blood mononuclear cells from eight samples each of cranial vessels with and without severe-stenosis radiophenotypes. Using DREAM sequencing profiling, 11 tags were detected in the promoter regions of the ACVR1C, ADCK5, EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PACSIN3, PAX8-AS1, TLDC1, and ZNF7 genes. Using methylation evaluation, we found that EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PAX8-AS1, and TLDC1 showed > 5% promoter methylation in non-plaque intima, atherosclerotic vascular tissues, and buffy coats. Using logistic regression analysis, we identified hypomethylation of MTNR1B as an independent variable for the stenosis radiophenotype prediction model by combining it with traditional atherosclerosis risk factors including age, hypertension history, and increases in creatinine, lipoprotein (a), and homocysteine. We performed fivefold cross-validation of the prediction model using 384 patients with ischemic stroke (50 [13%] no-stenosis and 334 [87%] > 1 stenosis radiophenotype). For the cross-validation, the training dataset included 70% of the dataset. The prediction model showed an accuracy of 0.887, specificity to predict stenosis radiophenotype of 0.940, sensitivity to predict no-stenosis radiophenotype of 0.533, and area under receiver operating characteristic curve of 0.877 to predict stenosis radiophenotype from the test dataset including 30% of the dataset. CONCLUSIONS: We identified and validated MTNR1B hypomethylation as an epigenetic marker to predict cranial vessel atherosclerosis using stenosis radiophenotypes and blood inflammatory cells rather than direct atherosclerotic plaque sampling.

Risk factors and stroke mechanisms in atherosclerotic stroke: intracranial compared with extracranial and anterior compared with posterior circulation disease.

BACKGROUND AND PURPOSE: The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis. METHODS: A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment. RESULTS: Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018-1.049), male gender (OR, 3.399; 95% CI, 2.335-4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117-2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274-2.618; P=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105-2.010; P=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005-5.890; P=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (P<0.001). CONCLUSIONS: The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

Apixaban for Secondary Stroke Prevention: Coexistant Cerebral Atherosclerosis May Increase Recurrent Strokes.

BACKGROUND AND PURPOSE: Oral anticoagulants are needed in stroke patients with atrial fibrillation (AF) for the prevention of recurrent stroke. However, the risk of major events or bleeding may be greater in stroke patients than in those without, because the presence of cerebral atherosclerosis or small vessel disease may increase these risks. This study aimed to investigate the outcomes of apixaban-treated stroke patients with AF and assess whether these factors are associated with the outcome. METHODS: This was a sub-analysis of stroke patients with AF enrolled in a prospective, open-label, multicenter, post-marketing surveillance study in South Korea, who were treated with apixaban and underwent magnetic resonance imaging (MRI) (Clinical trial registration: NCT01885598). RESULTS: A total of 651 patients (mean age, 72.5±8.7 years) received apixaban for a mean duration of 82.7±37.4 weeks. Fifty-three bleeding events occurred in 39 patients (6.0%), and 10 (1.5%) experienced major bleeding. Seventeen patients (2.6%) had major events (stroke, n=15, 2.3%; all ischemic), systemic embolism (n=1, 0.2%), and death (n=3, 0.5%). MRI data showed no significant association between white matter ischemic changes and microbleeds, and major events or bleeding. Patients with cerebral atherosclerotic lesions had a higher rate of major events than those without (4.6% [n=10/219] vs. 1.7% [n=7/409], P=0.0357), which partly explains the increased prevalence of major outcomes in this group versus patients without stroke (0.7%, P=0.0002). CONCLUSIONS: Apixaban is generally safe for patients with ischemic stroke. Increased primary outcomes in stroke patients may in part be attributed to the presence of cerebral atherosclerotic lesions, suggesting that further studies are needed to establish therapeutic strategies in this population.

Comparisons of Prehospital Delay and Related Factors Between Acute Ischemic Stroke and Acute Myocardial Infarction.

Background Prehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI. Methods and Results We identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed-effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1-person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off-hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI. Conclusions The effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.

Interpretation of TCD spectral patterns detected during carotid artery stent interventions.

PURPOSE: To classify transcranial Doppler (TCD) spectral patterns and analyze the significance of the patterns in the determination of hemodynamic alterations occurring during filter-protected carotid artery stent (CAS) procedures. METHODS: Data on middle cerebral artery (MCA) monitoring and post-CAS diffusion weighted magnetic resonance imaging (DWMRI) were reviewed for 53 patients (45 men; mean age 67.6 ± 8.3 years) who underwent TCD evaluation before CAS and TCD monitoring during the procedure. TCD spectral patterns were classified according to the hemodynamic changes that occurred after different portions of the CAS procedures. The relationships among the spectral patterns and the frequency and location of new DWMRI lesions were analyzed. RESULTS: TCD spectral changes were classified into 4 patterns: (1) microemboli signals (53, 100%), (2) right-left collateral signals (31/53, 58%), (3) spectral suppression after balloon inflation (31/44, 70%), and (4) continuous spectral suppression after balloon removal (4/44, 9%). Even though microembolic signals were frequently observed during CAS, the new DWMRI lesions were more frequently observed outside of the cerebral territory (78%) rather than in the territory ipsilateral to CAS (47%). The presence of right-left collaterals was related to less severe balloon-related spectral suppression on ipsilateral MCA (p<0.05). Continuous spectral suppression appeared after stent deployment and balloon dilation and was immediately reversed after removal of the filter device. CONCLUSION: The spectral patterns classified in the present study may prove useful in anticipating CAS procedure-related hemodynamic alterations. Close hemodynamic observation using these spectral patterns could be helpful in preventing serious complications during CAS.