Publications by authors named "Jae-Kwan Cha"

142 Publications

Long-Term Changes in Post-Stroke Depression, Emotional Incontinence, and Anger.

J Stroke 2021 May 31;23(2):263-272. Epub 2021 May 31.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background And Purpose: Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied.

Methods: This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim's criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP.

Results: A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P<0.01) decreased, while the prevalence of PSD (35.6%, 44.6%; P=0.03) and mean MADRS (6.16, 8.67; P<0.01) increased at LTP. ESSI was associated with PSD and PSA, but not with PSEI. The effect of the baseline National Institutes of Health Stroke Scale score on PSD decreased over time. The effect of low social support on PSD was greater than that of mRS at LTP.

Conclusions: The prevalence and degree of PSD significantly increased, while those of PSEI and PSA decreased at LTP. PSD in this stage appeared to be more closely associated with a lack of social support than patients' physical disabilities.
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http://dx.doi.org/10.5853/jos.2020.04637DOI Listing
May 2021

Treatment Intensification for Elevated Blood Pressure and Risk of Recurrent Stroke.

J Am Heart Assoc 2021 Apr 31;10(7):e019457. Epub 2021 Mar 31.

Department of Neurology and Cerebrovascular Center Seoul National University Bundang HospitalSeoul National University College of Medicine Seongnam Republic of Korea.

Background It remains unclear whether physicians' attitudes toward timely management of elevated blood pressure affect the risk of stroke recurrence. Methods and Results From a multicenter stroke registry database, we identified 2933 patients with acute ischemic stroke who were admitted to participating centers in 2011, survived at the 1-year follow-up period, and returned to outpatient clinics ≥2 times after discharge. As a surrogate measure of physicians' attitude, individual treatment intensification (TI) scores were calculated by dividing the difference between the frequencies of observed and expected medication changes by the frequency of clinic visits and categorizing them into 5 groups. The association between TI groups and the recurrence of stroke within 1 year was analyzed using hierarchical frailty models, with adjustment for clustering within each hospital and relevant covariates. Mean±SD of the TI score was -0.13±0.28. The TI score groups were significantly associated with increased risk of recurrent stroke compared with Group 3 (TI score range, -0.25 to 0); Group 1 (range, -1 to -0.5), adjusted hazard ratio (HR) 13.43 (95% CI, 5.95-30.35); Group 2 (range, -0.5 to -0.25), adjusted HR 4.59 (95% CI, 2.01-10.46); and Group 4 (TI score 0), adjusted HR 6.60 (95% CI, 3.02-14.45); but not with Group 5 (range, 0-1), adjusted HR 1.68 (95% CI, 0.62-4.56). This elevated risk in the lowest TI score groups persisted when confining analysis to those with hypertension, history of blood pressure-lowering medication, no atrial fibrillation, and regular clinic visits and stratifying the subjects by functional capacity at discharge. Conclusions A low TI score, which implies physicians' therapeutic inertia in blood pressure management, was associated with a higher risk of recurrent stroke. The TI score may be a useful performance indicator in the outpatient clinic setting to prevent recurrent stroke.
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http://dx.doi.org/10.1161/JAHA.120.019457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174371PMC
April 2021

Effect of Transport Time on the Use of Reperfusion Therapy for Patients with Acute Ischemic Stroke in Korea.

J Korean Med Sci 2021 Mar 22;36(11):e77. Epub 2021 Mar 22.

Department of Neurology, University of California San Francisco, San Francisco, CA, USA.

Background: We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke.

Methods: We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society.

Results: Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time ( = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes.

Conclusion: The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.
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http://dx.doi.org/10.3346/jkms.2021.36.e77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985286PMC
March 2021

Pre-diabetes is a predictor of short-term poor outcomes after acute ischemic stroke using IV thrombolysis.

BMC Neurol 2021 Feb 13;21(1):72. Epub 2021 Feb 13.

Stroke Center, Department of Neurology, College of Medicine, Dong-A University, 1,3Ga, Dongdaeshin-Dong, Seo-Gu, Busan, 602-715, South Korea.

Backgrounds: Pre-diabetes is an intermediate state between normal glucose metabolism and diabetes. Recent studies suggest that the presence of pre-diabetes is associated with poor outcomes after AIS. However, the results have been controversial. This study examines whether pre-diabetes influences the patients' short and long-term outcomes for AIS using IV thrombolysis.

Methods: We enrolled 661 AIS patients with IV thrombolysis. Based on the 2010 ADA guidelines, patients were classified as pre-diabetes, with HbA1c levels of 5.7-6.4%; diabetes, with HbA1c levels more than 6.5%; and NGM (normal glucose metabolism), with HbA1c levels less than 5.7%. We investigated short-term outcomes, including early neurologic deterioration (END), in-hospital death, and poor functional outcomes (mRS > 2) at 90 days. As for long-term outcomes, poor functional outcomes were measured at 1 year.

Results: Of the 661 AIS patients treated with IV thrombolysis, 197 patients (29.8%) were diagnosed with pre-diabetes, and 210 (31.8%) were diagnosed with diabetes. In a multivariate analysis, pre-diabetes was an independent predictor for END (OR = 2.02; 95% CI 1.12-3.62; p = 0.02) and in-hospital death (OR = 3.12; 95% CI 1.06-9.09; p = 0.04). On the other hand, diabetes was a significant independent factor for poor long-term outcomes (OR = 1.75; 95% CI 1.09-2.78; p = 0.02) after correcting confounding factors.

Conclusions: Unlike diabetes, pre-diabetes can be an important predictor of short-term outcomes after AIS. However, a more detailed research is needed to specify the precise mechanisms through which pre-diabetes affects the prognosis of acute ischemic stroke.
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http://dx.doi.org/10.1186/s12883-021-02102-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881609PMC
February 2021

CHA2DS2-VASc score in acute ischemic stroke with atrial fibrillation: results from the Clinical Research Collaboration for Stroke in Korea.

Sci Rep 2021 Jan 12;11(1):793. Epub 2021 Jan 12.

Department of Neurology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea.

We investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21-8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93-35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06-1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (P = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.
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http://dx.doi.org/10.1038/s41598-020-80874-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804950PMC
January 2021

Five-Year Risk of Acute Myocardial Infarction After Acute Ischemic Stroke in Korea.

J Am Heart Assoc 2021 Jan 29;10(1):e018807. Epub 2020 Dec 29.

Department of Neurology College of Medicine Soonchunhyang University Hospital Seoul Republic of Korea.

Background The long-term incidence of acute myocardial infarction (AMI) in patients with acute ischemic stroke (AIS) has not been well defined in large cohort studies of various race-ethnic groups. Methods and Results A prospective cohort of patients with AIS who were registered in a multicenter nationwide stroke registry (CRCS-K [Clinical Research Collaboration for Stroke in Korea] registry) was followed up for the occurrence of AMI through a linkage with the National Health Insurance Service claims database. The 5-year cumulative incidence and annual risk were estimated according to predefined demographic subgroups, stroke subtypes, a history of coronary heart disease (CHD), and known risk factors of CHD. A total of 11 720 patients with AIS were studied. The 5-year cumulative incidence of AMI was 2.0%. The annual risk was highest in the first year after the index event (1.1%), followed by a much lower annual risk in the second to fifth years (between 0.16% and 0.27%). Among subgroups, annual risk in the first year was highest in those with a history of CHD (4.1%) compared with those without a history of CHD (0.8%). The small-vessel occlusion subtype had a much lower incidence (0.8%) compared with large-vessel occlusion (2.2%) or cardioembolism (2.4%) subtypes. In the multivariable analysis, history of CHD (hazard ratio, 2.84; 95% CI, 2.01-3.93) was the strongest independent predictor of AMI after AIS. Conclusions The incidence of AMI after AIS in South Korea was relatively low and unexpectedly highest during the first year after stroke. CHD was the most substantial risk factor for AMI after stroke and conferred an approximate 5-fold greater risk.
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http://dx.doi.org/10.1161/JAHA.120.018807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955456PMC
January 2021

Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Mild-to-Moderate Acute Ischemic Stroke According to the Risk of Recurrent Stroke: An Analysis of 15 000 Patients From a Nationwide, Multicenter Registry.

Circ Cardiovasc Qual Outcomes 2020 11 17;13(11):e006474. Epub 2020 Nov 17.

Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, Korea (S.I.S., J.-H.H.).

Background: This study compared the effectiveness of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin with that of aspirin monotherapy (AM) in mild-to-moderate acute ischemic stroke considering the risk of recurrent stroke using the Stroke Prognosis Instrument II (SPI-II) score.

Methods: This study is a retrospective analysis of data from a prospective, nationwide, multicenter stroke registry database between January 2011 and July 2018. We included patients with mild-to-moderate (National Institutes of Health Stroke Scale score ≤10), acute (within 24 hours of onset), noncardioembolic ischemic stroke. The primary outcome was a 3-month composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality. Propensity scores using the inverse probability of treatment weighting method were used to mitigate baseline imbalances between the DAPT and AM groups and within each subgroup considering SPI-II scores.

Results: Among the 15 430 patients (age, 66±13 years; men, 62.0%), 45.1% (n=6960) received DAPT and 54.9% (n=8470) received AM. Primary outcome events were significantly more frequent in the AM group (16.7%) than in the DAPT group (15.5%; =0.03). Weighted Cox proportional hazards models showed a reduced risk of 3-month primary vascular events in the DAPT group versus the AM group (hazard ratio, 0.84 [0.78-0.92]; <0.001), with no interaction between acute treatment type and SPI-II risk subgroups (=0.44). However, among the high-risk patients with SPI-II scores >7, a substantially larger absolute benefit was observed for 3-month composite vascular events in the DAPT group (weighted absolute risk differences, 5.4%), whereas smaller absolute benefits were observed among patients in the low- or medium-risk SPI-II subgroups (1.7% and 2.4%, respectively).

Conclusions: Treatment with clopidogrel-aspirin was associated with a reduction in 3-month vascular events compared with AM in mild-to-moderate acute noncardioembolic ischemic stroke patients. Larger magnitudes of the effects of DAPT with clopidogrel-aspirin were observed in the high-risk subgroup by SPI-II risk scores.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006474DOI Listing
November 2020

Impact of Neurointensivist Co-Management in a Semiclosed Neurocritical-Care Unit.

J Clin Neurol 2020 Oct;16(4):681-687

Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea.

Background And Purpose: The importance of the specialized management of neurocritical patients is being increasingly recognized. We evaluated the impact of neurointensivist comanagement on the clinical outcomes (particularly the mortality rate) of neurocritical patients admitted to a semiclosed neurocritical-care unit (NCU).

Methods: We retrospectively included neurocritical patients admitted to the NCU between March 2015 and February 2018. We analyzed the clinical data and compared the outcomes between patients admitted before and after the initiation of neurointensivist co-management in March 2016.

Results: There were 1,785 patients admitted to the NCU during the study period. Patients younger than 18 years (=28) or discharged within 48 hours (=200) were excluded. The 1,557 remaining patients comprised 590 and 967 who were admitted to the NCU before and after the initiation of co-management, respectively. Patients admitted under neurointensivist co-management were older and had higher Acute Physiologic Assessment and Chronic Health Evaluation II scores. The 30-day mortality rate was significantly lower after neurointensivist co-management (=0.042). A multivariate logistic regression analysis demonstrated that neurointensivist co-management significantly reduced mortality rates in the NCU and in the hospital overall [odds ratio=0.590 (=0.002) and 0.585 (=0.001), respectively].

Conclusions: Despite the higher severity of the condition during neurointensivist co-management, co-management significantly improved clinical outcomes (including the mortality rate) in neurocritical patients.
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http://dx.doi.org/10.3988/jcn.2020.16.4.681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541986PMC
October 2020

Risk of recurrent stroke and antiplatelet choice in breakthrough stroke while on aspirin.

Sci Rep 2020 10 7;10(1):16723. Epub 2020 Oct 7.

Department of Neurology, Cerebrovascular Center, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictive risk score for future vascular events, the Essen Stroke Risk Score (ESRS). A total of 2348 patients (age, 69 ± 11 years; male, 57.7%) were analyzed, and 55.3%, 25.3% and 19.4% were treated with clopidogrel-aspirin, aspirin and clopidogrel, respectively. While the likelihood of choosing clopidogrel-aspirin increased as the ESRS increased, the likelihood of choosing aspirin decreased as the ESRS increased (P < 0.001). The ESRS category (0-1/2-3/ ≥ 4) modified the effect of antiplatelet regimens for 1-year vascular events (P < 0.01). Among patients with ESRS ≥ 4, clopidogrel-aspirin (HR 0.47 [0.30-0.74]) and clopidogrel (HR 0.30 [0.15-0.60]) significantly reduced the risk of outcome events. Our study showed that more than half of the patients with aspirin failure were treated with clopidogrel-aspirin. In particular, a higher ESRS, which indicates an increased risk of recurrent stroke, was associated with the choice of clopidogrel-aspirin rather than aspirin.
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http://dx.doi.org/10.1038/s41598-020-73836-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541489PMC
October 2020

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

J Geriatr Psychiatry Neurol 2020 Sep 10:891988720957108. Epub 2020 Sep 10.

Clinical Research Center, Asan Medical Center, Seoul, Korea.

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.
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http://dx.doi.org/10.1177/0891988720957108DOI Listing
September 2020

Neurologic deterioration in patients with acute ischemic stroke or transient ischemic attack.

Neurology 2020 10 14;95(16):e2178-e2191. Epub 2020 Aug 14.

From the Department of Neurology (T.H.P., M.-S.P., S.-S.P.), Seoul Medical Center; Department of Neurology, Cerebrovascular Center (J.-K.L., J.K., B.J.K., M.-K.H., H.-J.B.), Seoul National University Bundang Hospital, Seongnam; Department of Neurology (K.-S.H., Y.-J.C.), Ilsan Paik Hospital, Inje University, Goyang; Department of Neurology (W.-S.R., D.-E.K.), Dongguk University Ilsan Hospital, Goyang; Department of Neurology (M.S.P., K.-H.C., J.-T.K.), Chonnam National University Hospital, Gwangju; Department of Neurology (Jun Lee), Yeungnam University Hospital, Daegu; Department of Neurology (J.-K.C., D.-H.K.), Dong-A University Hospital, Busan; Department of Neurology (J.G.K., S.J.L.), Eulji University Hospital, Eulji University, Daejeon; Department of Neurology (J.-H.K., W.-J.K.), Ulsan University College of Medicine; Department of Neurology (D.-I.S., M.-J.Y.), Chungbuk National University Hospital, Cheongju; Department of Neurology (S.I.S., J.-H.H.), Keimyung University Dongsan Medical Center, Daegu; Clinical Research Center (J.S.L.), Asan Medical Center, Seoul; Department of Neurology (J.C.C.), Jeju National University Hospital, Jeju National University School of Medicine; Department of Neurology (B.-C.L., K.-H.Y., M.-S.O.), Hallym University Sacred Heart Hospital, Anyang; Department of Neurology (J.-M.P., K.K.), Eulji General Hospital, Eulji University, Seoul; Department of Neurology (K.B.L.), Soonchunhyang University Hospital, Seoul; Department of Biostatistics (Juneyoung Lee), Korea University College of Medicine, Seoul; and Department of Neurology (P.B.G.), Northwestern University Feinberg School of Medicine, Davee, Chicago, IL.

Objective: To improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS).

Methods: In this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed.

Results: ND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24-48 hours, and 0.66 within 72-96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3-6) at 3 months and 1 year were 1.75 (1.70-1.80) and 1.70 (1.65-1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45-1.74).

Conclusions: ND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke.
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http://dx.doi.org/10.1212/WNL.0000000000010603DOI Listing
October 2020

Effectiveness of Adding Antiplatelets to Oral Anticoagulants in Patients with Acute Ischemic Stroke with Atrial Fibrillation and Concomitant Large Artery Steno-Occlusion.

Transl Stroke Res 2020 12 29;11(6):1322-1331. Epub 2020 May 29.

Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea.

We investigated the effectiveness of adding antiplatelet (AP) to oral anticoagulant (OAC) treatment versus OAC treatment alone in patients with AIS with atrial fibrillation (AF) and significant large artery steno-occlusion (LASO). This study is a retrospective analysis of a nationwide, prospective, multicenter stroke registry between April 2008 and November 2017. Patients with acute (within 48 h of onset) and mild-to-moderate (NIHSS score ≤ 15) stroke with AF and concomitant LASO were identified. Antithrombotic regimens at discharge were categorized into OAC alone or OAC + AP. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 3 months of stroke. Among the 2553 patients (age, 73 ± 10 years; men, 50.4%), 78.8% were treated with OAC alone, and 21.2% were treated with OAC + AP. The primary outcome events were significantly more common in the OAC + AP group (6.7%) than the OAC alone group (4.3%) (p = 0.02). Weighted Cox proportional hazard analysis showed that OAC + AP increased the risk of 3-month primary outcome events compared with OAC alone (HR, 1.62 [1.06 to 2.46]). A potential interaction between the type of LASO and discharge antithrombotics was suggested (P = 0.04); unlike in patients with complete occlusion (OAC + AP; HR, 2.00 [1.27-3.15]), OAC + AP was comparable with OAC alone for 3-month primary outcome in patients with moderate-to-severe stenosis (HR, 0.54 [0.17-1.70]). In conclusion, OAC + AP might increase the risk of 3-month outcome events compared with OAC alone in patients with AIS with AF and concomitant LASO. However, the effect of additional AP to OAC might differ according to LASO type.
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http://dx.doi.org/10.1007/s12975-020-00822-zDOI Listing
December 2020

Promoter methylation changes in ALOX12 and AIRE1: novel epigenetic markers for atherosclerosis.

Clin Epigenetics 2020 05 12;12(1):66. Epub 2020 May 12.

Department of Neurology and Neuroepigenetics Laboratory, School of Medicine and Hospital, Chungnam National University, Daejeon, South Korea.

Background: Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients.

Results: Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima.

Conclusions: Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.
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http://dx.doi.org/10.1186/s13148-020-00846-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218560PMC
May 2020

Statin therapy in acute cardioembolic stroke with no guidance-based indication.

Neurology 2020 05 9;94(19):e1984-e1995. Epub 2020 Apr 9.

From the Department of Neurology (H.-K.P., K.-S.H., Y.-J.C.), Inje University Ilsan Paik Hospital, Goyang; Clinical Research Center (J.S.L.), Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine; Department of Neurology (J.-M.P., K.K.), Nowon Eulji Medical Center, Eulji University, Seoul; Department of Neurology (S.J.L., J.G.K.), Eulji University Hospital, Eulji University, Daejeon; Department of Neurology (J.-K.C., D.-H.K., H.-W.N.), Dong-A University Hospital, Busan; Department of Neurology (M.-K.H., B.J.K., H.-J.B.), Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam; Department of Neurology (T.H.P., S.-S.P.), Seoul Medical Center; Department of Neurology (K.B.L.), Soonchunhyang University Hospital, Seoul; Department of Neurology (Jun Lee), Yeungnam University Hospital, Daegu; Department of Neurology (B.-C.L., K.-H.Y., M.S.O.), Hallym University Sacred Heart Hospital, Anyang; Department of Neurology (J.-T.K., K.-H.C.), Chonnam National University Hospital, Gwangju; Department of Neurology (D.-E.K., W.-S.R.), Dongguk University Ilsan Hospital, Goyang; Department of Neurology (J.C.C.), Jeju National University Hospital, Jeju National University School of Medicine; Department of Neurology (J.-H.K., W.-J.K.), Ulsan University College of Medicine; Department of Neurology (D.-I.S.), Chungbuk University Hospital, Cheongju; Department of Neurology (S.I.S., J.-H.H.), Keimyung University Dongsan Medical Center, Daegu; Department of Biostatistics (Juneyoung Lee), Korea University College of Medicine, Seoul; Department of Translational Science and Molecular Medicine (P.B.G.), Michigan State University College of Human Medicine; and Mercy Health Hauenstein Neurosciences (P.B.G.), Grand Rapids, MI.

Objective: It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population.

Methods: Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes.

Results: Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers ( < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death.

Conclusion: Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.
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http://dx.doi.org/10.1212/WNL.0000000000009397DOI Listing
May 2020

Atrial Fibrillation-Associated Ischemic Stroke Patients With Prior Anticoagulation Have Higher Risk for Recurrent Stroke.

Stroke 2020 04 26;51(4):1150-1157. Epub 2020 Feb 26.

Department of Cerebrovascular Medicine (M.K., T.M., S.Y., K. Toyoda), National Cerebral and Cardiovascular Center, Suita, Japan.

Background and Purpose- Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation. Methods- This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event. Results- Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69-81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335-365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02-2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups. Conclusions- The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502.
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http://dx.doi.org/10.1161/STROKEAHA.119.027275DOI Listing
April 2020

Influence of Hemoglobin Concentration on Stroke Recurrence and Composite Vascular Events.

Stroke 2020 04 11;51(4):1309-1312. Epub 2020 Feb 11.

Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Korea (B.J.K., H.-J.B., M.-K.H.).

Background and Purpose- We evaluated whether hemoglobin concentration at admission was associated with stroke recurrence and composite vascular events (stroke, myocardial infarction, and vascular death) in acute ischemic stroke. Methods- We collected data from patients with acute ischemic stroke or transient ischemic attack from a multicenter stroke registry database in Korea. The association of hemoglobin concentration with 1-year stroke recurrence and composite vascular events was evaluated with respect to age, presence of cerebral artery stenosis, stroke severity, and stroke subtype. Results- Hemoglobin levels were inversely associated with stroke recurrence and composite vascular events. One-year rates of stroke recurrence and composite vascular events were significantly higher in patients with anemia or moderate anemia. In multivariable analyses, moderate anemia remained an independent predictor of stroke recurrence (adjusted hazard ratio, 1.43 [95% CI, 1.16-1.75]) and composite vascular events (adjusted hazard ratio, 1.26 [95% CI, 1.07-1.48]). Moderate anemia increased the risk of composite vascular events in patients with mild-to-moderate stroke severity (National Institutes of Health Stroke Scale score <16, =0.01 for interaction). Conclusions- Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.
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http://dx.doi.org/10.1161/STROKEAHA.119.028058DOI Listing
April 2020

Development of stroke identification algorithm for claims data using the multicenter stroke registry database.

PLoS One 2020 14;15(2):e0228997. Epub 2020 Feb 14.

Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.

Background: Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected.

Methods: From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database.

Results: Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively.

Conclusions: Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228997PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021298PMC
May 2020

Three-month modified Rankin Scale as a determinant of 5-year cumulative costs after ischemic stroke: An analysis of 11,136 patients in Korea.

Neurology 2020 03 6;94(9):e978-e991. Epub 2020 Feb 6.

Department of Neurology and Cerebrovascular Center (S.-E.K., J.Y.K., K.-J.L, J.K., B.J.K, M.-K.H., H.-J.B) and Department of Clinical Preventive Medicine (H.L.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam; Department of Neurology (K.-H.C, J.-T.K.), Chonnam National University Hospital, Gwangju; Department of Neurology (D.-I.S., M.-J.Y.), Chungbuk National University Hospital, Cheongju; Department of Neurology (J.-K.C., D.-H.K., H.-W.N.), Dong-A University Hospital, Dong-A University College of Medicine, Busan; Department of Neurology (D.-E.K., W.-S.R.), Dongguk University Ilsan Hospital, Goyang; Department of Neurology (J.-M.P., K.K.), Eulji General Hospital, Seoul; Department of Neurology (J.-G.K., S.J.L.), Eulji University Hospital, Eulji University, Daejeon; Department of Neurology (M.-S.O., K.-H.Y., B.-C.L.), Hallym University Sacred Heart Hospital, Anyang; Department of Neurology (H.-K.P., K.-S.H., Y.-J.C.), Ilsan Paik Hospital, Inje University, Goyang; Department of Neurology (J.C.C.), Jeju National University Hospital, Jeju National University School of Medicine; Department of Neurology (S.I.S., J.-H.H.), Keimyung University Dongsan Medical Center, Daegu; Department of Neurology (M.-S.P., T.H.P., S.-S.P.), Seoul Medical Center; Department of Neurology (K.B.L.), Soonchunhyang University Hospital, College of Medicine, Seoul; Department of Neurology (J.-H.K., W.-J.K.), Ulsan University Hospital, Ulsan University College of Medicine; Department of Neurology (Jun Lee), Yeungnam University Hospital, Daegu; Clinical Research Center (J.S.L.), Asan Medical Center; Department of Biostatistics (Juneyoung Lee), Korea University College of Medicine, Seoul, Republic of Korea; Department of Neurology (A.M.), Helsinki University Central Hospital, Finland; and Davee Department of Neurology (P.B.G.), Northwestern University Feinberg School of Medicine, Chicago, IL.

Objective: Stroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials.

Methods: We analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score.

Results: Between January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0-5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score ( < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke.

Conclusions: We show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.
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http://dx.doi.org/10.1212/WNL.0000000000009034DOI Listing
March 2020

Hospital Volume Threshold Associated with Higher Survival after Endovascular Recanalization Therapy for Acute Ischemic Stroke.

J Stroke 2020 Jan 31;22(1):141-149. Epub 2020 Jan 31.

Department of Health Policy and Management, Seoul National University College of Medicine, Seoul, Korea.

Background And Purpose: Endovascular recanalization therapy (ERT) is becoming increasingly important in the management of acute ischemic stroke (AIS). However, the hospital volume threshold for optimal ERT remains unknown. We investigated the relationship between hospital volume of ERT and risk-adjusted patient outcomes.

Methods: From the National Health Insurance claims data in Korea, 11,745 patients with AIS who underwent ERT from July 2011 to June 2016 in 111 hospitals were selected. We measured the hospital's ERT volume and patient outcomes, including the 30-day mortality, readmission, and postprocedural intracranial hemorrhage (ICH) rates. For each outcome measure, we constructed risk-adjusted prediction models incorporating demographic variables, the modified Charlson comorbidity index, and the stroke severity index (SSI), and validated them. Risk-adjusted outcomes of AIS cases were compared across hospital quartiles to confirm the volume-outcome relationship (VOR) in ERT. Spline regression was performed to determine the volume threshold.

Results: The mean AIS volume was 14.8 cases per hospital/year and the unadjusted means of mortality, readmission, and ICH rates were 11.6%, 4.6%, and 8.6%, respectively. The VOR was observed in the risk-adjusted 30-day mortality rate across all quartile groups, and in the ICH rate between the first and fourth quartiles (P<0.05). The volume threshold was 24 cases per year.

Conclusions: There was an association between hospital volume and outcomes, and the volume threshold in ERT was identified. Policies should be developed to ensure the implementation of the AIS volume threshold for hospitals performing ERT.
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http://dx.doi.org/10.5853/jos.2019.00955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005355PMC
January 2020

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial.

J Stroke 2020 Jan 31;22(1):108-118. Epub 2020 Jan 31.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background And Purpose: Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study.

Methods: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm.

Results: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint.

Conclusions: Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.
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http://dx.doi.org/10.5853/jos.2019.02551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005357PMC
January 2020

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

Cerebrovasc Dis 2020 5;49(1):19-25. Epub 2020 Feb 5.

College of Nursing, The Research Institute of Nursing Science, Seoul National University, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1159/000506116DOI Listing
September 2020

Evaluation of neutrophil extracellular traps as the circulating marker for patients with acute coronary syndrome and acute ischemic stroke.

J Clin Lab Anal 2020 May 6;34(5):e23190. Epub 2020 Jan 6.

Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea.

Introduction: Neutrophil extracellular traps (NETs) are known to be induced by various factors. In this study, we tried to identify circulating levels of NETs in patients with acute coronary syndrome (ACS) and acute ischemic stroke (AIS) and to confirm its suitability as a new circulating marker in their detection.

Methods: We prospectively enrolled 95 patients with a diagnosis of ACS (N = 37) or AIS (N = 58) in Dong-A University Hospital, Busan, Korea. The control group was selected from healthy adults (N = 25) who visited the hospital for health screening. Circulating levels of NETs were evaluated by measuring plasma concentrations of double-stranded DNA (dsDNA) and DNA-histone complex.

Results: The concentrations of dsDNA were statistically higher in patients with ACS or AIS than those in the control group (both P < .001). In the univariable and multivariable analyses, statistically significant risk factors were troponin I (TnI) level and dsDNA concentration in the ACS group (P = .046 and P = .015, respectively) and only dsDNA concentration in the AIS group (P = .002). In the receiver operating characteristic curve analyses, the area under the curve values for TnI level and dsDNA concentration in the ACS group were 0.878 and 0.968, respectively, and the value for dsDNA concentration in the AIS group was 0.859.

Conclusions: In this study, it was confirmed that the circulating level of NETs was increased in patients with ACS and AIS at initial presentation. Findings in this study show that NETs could be used as a new circulating marker for the initial diagnosis of ACS or AIS.
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http://dx.doi.org/10.1002/jcla.23190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246366PMC
May 2020

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Stroke 2020 03 20;51(3):931-937. Epub 2019 Dec 20.

Department of Neurology (S.U.K., D.-W.K.), Asan Medical Center, Ulsan University, Seoul, Korea.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke ( for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; =0.01). A marginal interaction between treatment group and white matter change on any stroke ( for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; =0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; =0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
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http://dx.doi.org/10.1161/STROKEAHA.119.023855DOI Listing
March 2020

Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation.

Stroke 2020 01 4;51(1):162-169. Epub 2019 Dec 4.

Mercy Health Hauenstein Neurosciences and Department of Translational Science and Molecular Medicine, Michigan State University College of Human Medicine, Grand Rapids (P.B.G.).

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.
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http://dx.doi.org/10.1161/STROKEAHA.119.026847DOI Listing
January 2020

A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

N Engl J Med 2020 01 18;382(1). Epub 2019 Nov 18.

From the Department of Neurology and Stroke Center (P.A., J.L., H.C., L.C., C.G., C.H., P.C.L., E.M., P.-J.T.) and the Department of Cardiology (J.A., G.D., P.G.S.), Assistance Publique-Hôpitaux de Paris (APHP), Bichat Hospital, Laboratory for Vascular Translational Science, INSERM Unité 1148, Département Hospitalo Universitaire-Fibrose Inflammation Remodelage, and the Department of Cardiology, Cochin Hospital (O.V.), University of Paris, the Department of Neurology, Foch Hospital (B.L.), Urgences Cerebrovasculaires (Y.S.), Centre de Pharmacoépidémiologie de l'APHP (N.Y.), and the Department of Endocrinology (E.B.), Hôpital de la Pitié-Salpêtrière, the Department of Biostatistics, APHP, Université Paris Diderot, Sorbonne Paris Cité, Fernand Widal Hospital (É.V.), and the Department of Endocrinology, Sorbonne University (E.B.), Paris, Équipe d'Accueil EA2694, Santé Publique: Epidémiologie et Qualité des Soins (J.L.), and the Department of Neurology, Stroke Unit, University of Lille, Centre Hospitalier Universitaire (CHU) de Lille (D.L.), Lille, the Department of Neurology, University Hospital of Dijon, University of Burgundy, Dijon (Y.B., M.G.), the Stroke Unit, Pasteur Hospital, Nice (M.-H.M.), Hospices Civils de Lyon, Department of Neurology and Stroke Center, Lyon University, Lyon (N.N.), the Department of Neurology, Versailles University Hospital, Versailles (F.P.), the Department of Vascular Neurology, Pellegrin Tripode Hospital, University of Bordeaux, Bordeaux (I.S.), and the Department of Neurology, Université Caen Normandie, CHU Caen Normandie, INSERM Unité 1237, Cyceron, Caen (E.T.) - all in France; Asan Medical Center (J.S.K.), the Department of Neurology, Eunpyeong St. Mary's Hospital, Catholic University of Korea (Y.-J.K.), and the Department of Neurology, Soonchunhyang University College of Medicine (K.-B.L.), Seoul, Dong-a University Hospital (J.-K.C.) and the Department of Neurology and Stroke Center, Pusan National University Hospital (S.M.S.), Busan, and the Department of Neurology, Hallym University Sacred Heart Hospital, Anyang (B.-C.L.) - all in South Korea; and the National Heart and Lung Institute-Imperial College and the Institute of Cardiovascular Medicine and Science-Royal Brompton Hospital, London (P.G.S.).

Background: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.

Methods: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.

Results: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.

Conclusions: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).
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http://dx.doi.org/10.1056/NEJMoa1910355DOI Listing
January 2020

Characteristics and management of stroke in Korea: 2014-2018 data from Korean Stroke Registry.

Int J Stroke 2020 08 22;15(6):619-626. Epub 2019 Oct 22.

Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.

Background: Lifestyle changes and evolving healthcare practices in Korea have influenced disease patterns and medical care. Since strokes have high disease burden in countries with aging populations, it is necessary to evaluate the associated recent disease characteristics and patient care patterns. The Korean Stroke Registry is a nationwide, multicenter, prospective, hospital-based stroke registry in Korea used to monitor these changes across the population.

Aims: We aimed to evaluate the recent status of clinical characteristics and management of stroke cases in order to identify changes in the Korean population across time.

Methods: This study used Korean Stroke Registry data from patients experiencing ischemic stroke or transient ischemic attack patients, between 2014 and 2018. We analyzed data on demographics, risk factors, stroke subtypes, and treatments that included thrombolysis.

Results: A total of 39,291 patients (mean age 68.0 ± 13.0, 58.3% male) were analyzed. The proportions of hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and prior stroke were 63.4%, 30.9%, 27.7%, 19.4%, and 17.1%, respectively. In the stroke subtype analysis, the frequency of large artery atherosclerosis was highest (32.6%), followed by cardioembolism (21.3%) and small vessel occlusion (19.9%). Acute reperfusion therapy was conducted in 15.3% of cases (11.7% using intravenous tPA and 7.3% using intra-arterial thrombectomy). Intra-arterial thrombectomy also demonstrated a steep increasing trend over time (RR 1.095 (1.060-1.131),  < 0.001).

Conclusions: This study provided analysis of nationwide, hospital-based, quality-controlled data from the Korean Stroke Registry database regarding changes in the characteristics, risk factors, and treatments of strokes in Korea.
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http://dx.doi.org/10.1177/1747493019884517DOI Listing
August 2020

Effect of the Number of Neurointerventionalists on Off-Hour Endovascular Therapy for Acute Ischemic Stroke Within 12 Hours of Symptom Onset.

J Am Heart Assoc 2019 11 18;8(21):e011933. Epub 2019 Oct 18.

Department of Neurology Hallym University Sacred Heart Hospital Anyang Korea.

Background Off-hour presentation can affect treatment delay and clinical outcomes in endovascular therapy (EVT) for acute ischemic stroke. We aimed to examine the treatment delays and clinical outcomes of EVT between on- and off-hour admission and to evaluate the effect of hospital procedure volume and the number of neurointerventionalists on off-hour EVT. Methods and Results From a multicenter registry, we identified patients who were treated with EVT within 12 hours of symptom. Annual hospital procedure volume was divided as low (<30), medium (30-60), and high (>60). The effect of the number of neurointerventionalists and annual hospital procedure volume on clinical outcome was estimated by the generalized estimation equation. Of the 31 133 stroke patients, 1564 patients met the eligibility criteria (mean age: 69±12 years; median baseline National Institutes of Health stroke scale score, 15 [interquartile range, 10-19]). Of 1564 patients, 893 (57.1%) arrived during off-hour. The off-hour patients had greater median door-to-puncture time (110  versus 95 minutes; <0.001) compared with on-hour patients. Despite the treatment delay, the functional outcome at 3 months did not differ between off- and on-hour (odds ratio with 95% CI for 3-month modified Rankin Scale 0-2, 0.99 [0.78-1.25]; =0.90). The presence of three neurointerventionalists was significantly associated with favorable outcomes at 3 months during on- and off-hour (2.07 [1.53-2.81]; <0.001). The association was not observed for annual hospital procedural volume and the functional outcomes. Conclusions The number of neurointerventionalists was more crucial to effective around-the-clock EVT for acute stroke patients than hospital procedural volume.
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http://dx.doi.org/10.1161/JAHA.119.011933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898823PMC
November 2019