RESUMEN
OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.
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CADASIL , Hemorragia Cerebral , Mutación , Receptor Notch3 , Humanos , Masculino , Femenino , Receptor Notch3/genética , Persona de Mediana Edad , CADASIL/genética , Estudios Retrospectivos , Hemorragia Cerebral/genética , Anciano , Mutación/genética , Adulto , Japón , República de Corea , Pueblo Asiatico/genéticaRESUMEN
OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.
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Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Arteria Basilar , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular/etiología , Trombectomía/efectos adversos , Hemorragias Intracraneales/etiología , Sistema de Registros , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.
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Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Anciano , Femenino , Humanos , Masculino , Administración Oral , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Sistema de RegistrosRESUMEN
OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Prevalencia , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Mutación/genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Receptores de Activinas Tipo II/genética , Adenosina Trifosfatasas/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). METHODS: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. RESULTS: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). CONCLUSIONS: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.
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Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Isquemia Encefálica/etiología , Estudios Prospectivos , Accidente Cerebrovascular Isquémico/complicaciones , Infarto Encefálico/complicaciones , Factores de Riesgo , RecurrenciaRESUMEN
BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Humanos , Adulto Joven , Adulto , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/terapia , Isquemia Encefálica/complicaciones , Estudios Prospectivos , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.
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Aterosclerosis , Isquemia Encefálica , Procedimientos Endovasculares , Hipertensión , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Trombectomía/métodos , Aterosclerosis/complicaciones , Hipertensión/complicaciones , Procedimientos Endovasculares/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.
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Disección Aórtica , Isquemia Encefálica , Trastornos Migrañosos , Neoplasias , Accidente Cerebrovascular , Adulto , Anciano , Disección Aórtica/complicaciones , Isquemia Encefálica/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Neoplasias/complicaciones , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
Carotid artery thrombosis following carotidynia is an uncommon manifestation of systemic lupus erythematosus. We report the case of a woman without evidence of a lupus flare-up who presented with the unusual clinical course of ipsilateral carotidynia and recurrent ischemic stroke due to carotid thrombosis. To our knowledge, this is the first case of such an unusual manifestation in lupus and highlights distinctive challenges in the diagnosis and management of carotid artery thrombosis following carotidynia.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedades de las Arterias Carótidas , Trombosis de las Arterias Carótidas , Accidente Cerebrovascular Isquémico , Lupus Eritematoso Sistémico , Accidente Cerebrovascular , Femenino , Humanos , Trombosis de las Arterias Carótidas/diagnóstico por imagen , Trombosis de las Arterias Carótidas/etiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Brote de los Síntomas , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Dolor , Accidente Cerebrovascular/etiologíaRESUMEN
This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.
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Aterosclerosis , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.
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Servicios Médicos de Urgencia , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Anciano , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/complicaciones , Hospitalización , República de Corea , GobiernoRESUMEN
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic disorder among those responsible for hereditary strokes, and it is caused by a mutation in the NOTCH3 gene on chromosome 19. Blood biomarkers related to the Notch signaling pathway have not been investigated extensively in CADASIL. In this study, we measured the serum and plasma levels of NOTCH3 extracellular domain (N3ECD) and its ligand, Jagged-1, in 279 healthy subjects. The levels of N3ECD and Jagged-1 showed significant correlations in both serum (p < 0.0001, r = 0.2681) and plasma (p < 0.0001, r = 0.4065). The N3ECD levels were significantly higher in the serum than in plasma and tend to increase with age. In contrast, there was no significant difference between the serum and plasma levels of Jagged-1 levels. To summarize, we were able to measure N3ECD and Jagged-1 protein levels in healthy human serum and plasma. Taken together, our findings provide the basis for further studies investigating the clinical use of blood N3ECD and Jagged-1 levels for CADASIL and other Notch signaling-related diseases.
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CADASIL , Biomarcadores , CADASIL/genética , Voluntarios Sanos , Humanos , Proteína Jagged-1/genética , Ligandos , Mutación , Receptor Notch3/genética , Receptores Notch/genéticaRESUMEN
BACKGROUND AND PURPOSE: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF). METHODS: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders. RESULTS: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14). CONCLUSIONS: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.
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Fibrilación Atrial , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Humanos , Modelos de Riesgos Proporcionales , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Delgadez/diagnóstico , Delgadez/epidemiologíaRESUMEN
Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 34). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.001.56) for ASVD 1, 1.34 (95% CI, 1.021.76) for ASVD 2, and 1.93 (95% CI, 1.242.99) for ASVD 34. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.011.74), 1.47 (1.062.03), and 2.39 (1.473.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.051.54]) and all-cause death (1.45 [1.171.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.
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Enfermedad de la Arteria Coronaria , Bases de Datos Factuales , Enfermedad Arterial Periférica , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Arteriosclerosis Intracraneal , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.
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Técnicas de Apoyo para la Decisión , Evaluación de la Discapacidad , Servicios Médicos de Urgencia , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico , Arteriosclerosis Intracraneal/fisiopatología , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
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 (P = 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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Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico/terapia , Terapia Trombolítica , Tiempo de Tratamiento , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Sistema de Registros , República de Corea , Factores de TiempoRESUMEN
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, P=0.01 for interaction). Conclusions- Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.
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Isquemia Encefálica/sangre , Isquemia Encefálica/diagnóstico , Hemoglobinas/metabolismo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Anciano , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Estudios Prospectivos , RecurrenciaRESUMEN
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.
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Fibrilación Atrial , Isquemia Encefálica , Frecuencia Cardíaca , Accidente Cerebrovascular , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Isquemia Encefálica/mortalidad , Isquemia Encefálica/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Background and Purpose- Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease. Methods- We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used. Results- A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57-0.88; P=0.002 and hazard ratio, 0.81; 95% CI, 0.69-0.96; P=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74-1.01; P=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke. Conclusions- Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.
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Aspirina/administración & dosificación , Aterosclerosis/tratamiento farmacológico , Clopidogrel/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/mortalidad , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/mortalidadRESUMEN
Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.