Body mass index and waist circumference as predictors of recurrent vascular events after a recent ischemic stroke.

OBJECTIVES: Although elevated body mass index (BMI) is a risk factor for stroke, it appears to protect against recurrent vascular events. We tried to evaluate BMI and waist circumference (WC) as predictors of recurrent stroke and vascular events in a cohort of stroke survivors who were followed for 12 months. MATERIALS AND METHODS: We analyzed the stroke registry database of 6 hospitals and recruited patients with a first-ever stroke who were admitted from January 2011 to November 2019 and had their BMI and WC measured. Cox proportional hazards models were used to compare risks of recurrent stroke and major vascular events (a composite of stroke, myocardial infarction, or vascular death) between different BMI and WC quintiles. Reference categories were patients in the lowest quintiles. RESULTS: A total of 14 781 patients were analyzed. Patients in the second quintile of BMI had the lowest risk of recurrent stroke (adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.58-0.91); patients in the highest quintile had the lowest risk or a major vascular event (adjusted HR 0.71; 95% CI 0.58-0.86). Patients in the fourth quintile of WC had the lowest risk of recurrent stroke (adjusted HR 0.73; 95% CI 0.59-0.91) and a major vascular event (adjusted HR 0.72; 95 % CI 0.60-0.86). CONCLUSIONS: Our results show favorable effects of excess body weight and intra-abdominal fat on avoidance of vascular events after stroke and a favorable effect of intra-abdominal fat on avoidance of recurrent stroke.

Biological Mechanism of Sex Difference in Stroke Manifestation and Outcomes.

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location. METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations. RESULTS: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001). DISCUSSION: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients.

Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial: Rationale and design.

RATIONALE: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. AIMS: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. METHODS AND STUDY DESIGN: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. STUDY OUTCOMES: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. DISCUSSION: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. TRIAL REGISTRATION: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Effectiveness and safety of EVT in patients with acute LVO and low NIHSS.

Background and purpose: There is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits. Methods: From a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS <6 presenting within 24 h from the time last known well (LKW) were included. Early neurological deterioration (END) developed before EVT was prospectively collected as an increasing total NIHSS score ≥2 or any worsening of the NIHSS consciousness or motor subscores during hospitalization not related to EVT. Significant hemorrhage was defined as PH2 hemorrhagic transformation or hemorrhage at a remote site. The modified Rankin Scale (mRS) was prospectively collected at 3 months. Results: Among 1,083 patients, 149 (14%) patients received EVT after a median of 5.9 [3.6-12.3] h after LKW. In propensity score-matched analyses, EVT was not associated with mRS 0-1 (matched OR 0.99 [0.63-1.54]) but increased the risk of a significant hemorrhage (matched OR, 4.51 [1.59-12.80]). Extraneous END occurred in 207 (19%) patients after a median of 24.5 h [IQR, 13.5-41.9 h] after LKW (incidence rate, 1.41 [95% CI, 1.23-1.62] per 100 person-hours). END unrelated to EVT showed a tendency to modify the effectiveness of EVT (P-for-interaction, 0.08), which decreased the odds of having mRS 0-1 in mild LVO patients without END (adjusted OR, 0.63 [0.40-0.99]). Conclusions: The use of EVT in patients with acute LVO and low NIHSS scores may require the assessment of individual risks of early deterioration, hemorrhagic complications and expected benefit.

Effect of Heart Rate on 1-Year Outcome for Patients With Acute Ischemic Stroke.

Background Previous literature about the effect of heart rate on poststroke outcomes is limited. We attempted to elucidate (1) whether heart rate during the acute period of ischemic stroke predicts subsequent major clinical events, (2) which heart rate parameter is best for prediction, and (3) what is the estimated heart rate cutoff point for the primary outcome. Methods and Results Eight thousand thirty-one patients with acute ischemic stroke who were hospitalized within 48 hours of onset were analyzed retrospectively. Heart rates between the 4th and 7th day after onset were collected and heart rate parameters including mean, time-weighted average, maximum, and minimum heart rate were evaluated. The primary outcome was the composite of recurrent stroke, myocardial infarction, and mortality up to 1 year after stroke onset. All heart rate parameters were associated with the primary outcome (P's<0.001). Maximum heart rate had the highest predictive power. The estimated cutoff point for the primary outcome was 81 beats per minute for mean heart rate and 100 beats per minute for maximum heart rate. Patients with heart rates above these cutoff points had a higher risk of the primary outcome (adjusted hazard ratio, 1.80 [95% CI, 1.57-2.06] for maximum heart rate and 1.65 [95% CI, 1.45-1.89] for mean heart rate). The associations were replicated in a separate validation dataset (N=10 000). Conclusions These findings suggest that heart rate during the acute period of ischemic stroke is a predictor of major clinical events, and optimal heart rate control might be a target for preventing subsequent cardiovascular events.

One-Year Blood Pressure Trajectory After Acute Ischemic Stroke.

Background Although the effect of blood pressure on poststroke outcome is well recognized, the long-term trajectory of blood pressure after acute ischemic stroke and its influence on outcomes have not been studied well. Methods and Results We analyzed systolic blood pressure (SBP) measurements in 5514 patients with acute ischemic stroke at ≥2 of 7 prespecified time points during the first year after stroke among those enrolled in a multicenter prospective registry. Longitudinal SBPs were categorized using a group-based trajectory model. The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause mortality up to 1 year after stroke. The study subjects were categorized into 4 SBP trajectory groups: low (27.0%), moderate (59.5%), persistently high (1.2%), and slowly dropping (12.4%). In the first 3 groups, SBP decreased during the first 3 to 7 days and remained steady thereafter. In the slowly dropping SBP group, SBPs decreased from 182 to 135 mm Hg during the first 30 days, then paralleled the trajectory of the moderate SBP group. Compared with the reference, the moderate SBP group, the slowly dropping SBP group was at higher risk for the primary outcome (adjusted hazard ratio [HR], 1.32; 95% CI, 1.05‒1.65) and mortality (adjusted HR, 1.35; 95% CI, 1.03‒1.78). Primary outcome rates were similarly high in the persistently high SBP group. Conclusions Four 1-year longitudinal SBP trajectories were identified in patients with acute ischemic stroke. Patients in the slowly dropping SBP and persistently high SBP trajectory groups were prone to adverse cardiovascular outcomes after stroke.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Comparative effectiveness of combined antiplatelet treatments in acute minor ischaemic stroke.

BACKGROUND: No study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel-aspirin) versus clopidogrel-aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke. METHODS: We identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel-aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months. RESULTS: Among 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel-aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel-aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel-aspirin group than in the other combination group (weighted HR: 0.82 (0.59-1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76-1.44)) or other combination group and the 3-month primary outcome. CONCLUSION: Other combined antiplatelet treatment, compared with aspirin alone or clopidogrel-aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel-aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Relation of Pre-Stroke Aspirin Use With Cerebral Infarct Volume and Functional Outcomes.

OBJECTIVE: We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS: This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS: The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score < 3), particularly in large artery atherosclerosis stroke and cardioembolic stroke (adjusted difference = 7.2%, 95% CI = 1.8 to 12.5 and adjusted difference = 6.4%, 95% CI = 1.7 to 11.1, respectively). Pre-stroke aspirin use (vs nonuse) was associated with 85% less frequent cerebral thrombus-related susceptibility vessel sign (SVS) in large artery atherosclerosis stroke (adjusted difference = -1.4%, 95% CI = -2.1 to -0.8, p < 0.001) and was associated with ~40% lower SVS volumes, particularly in cardioembolic stroke (adjusted difference = -0.16 cm3 , 95% CI = -0.29 to -0.02, p = 0.03). Moreover, pre-stroke aspirin use was not significantly associated with hemorrhagic transformation (adjusted difference = -1.1%, p = 0.09). INTERPRETATION: Pre-stroke aspirin use associates with improved functional independence in patients with first-ever ischemic large arterial stroke by reducing infarct volume and/or END, likely by decreasing thrombus burden, without increased risk of hemorrhagic transformation. ANN NEUROL 2021;90:763-776.

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

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.

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

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

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.

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%; P=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]; P<0.001), with no interaction between acute treatment type and SPI-II risk subgroups (Pinteraction=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.

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

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.

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

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 (Pinteraction = 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.

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

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 (p < 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.

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

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.

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

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 (p < 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.

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

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 (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>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.