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BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.
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Hemorragia Cerebral , Fibrinolíticos , Sistema de Registros , Humanos , Masculino , Femenino , Anciano , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/inducido químicamente , Dinamarca/epidemiología , Persona de Mediana Edad , Fibrinolíticos/efectos adversos , Anciano de 80 o más Años , Inhibidores de Agregación Plaquetaria/efectos adversos , Anticoagulantes/efectos adversos , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Aspirina/efectos adversos , IncidenciaRESUMEN
Introduction: Symptom recognition and timely access to treatment are critical components of acute stroke care systems. Two mnemonics widely used in public educational campaigns for recognizing stroke symptoms include FAST (Face-Arm-Speech-Time) and BEFAST (Balance-Eyes-Face-Arm Speech-Time). The FAST mnemonic can miss up to 14% of strokes. BEFAST includes common posterior circulation stroke symptoms and has been implemented by several Comprehensive Stroke Centers (CSCs). Methods: We sought to analyze the pattern of public educational materials available on the websites of US CSCs. The Joint Commission (JC) quality check website compiles a list containing the names and locations of the country's 217 JC-certified CSCs, which was downloaded in August, 2022. Each CSC's website was searched for educational material containing FAST and BEFAST mnemonics for stroke symptom recognition. Results: The FAST mnemonic was listed by 35% of CSCs, the BEFAST by 58%, with 7% listing no specific mnemonic. The highest portion of CSCs using BEFAST was in western (65%) and southeastern (63%) states. The highest percentage of CSCs with no listed mnemonic were in the northeastern (14%) and southeastern (13%) states. Conclusion: Consistency is critical in shaping public health education related to stroke symptoms recognition. Our study suggests further effort is needed to unify the public messaging on stroke recognition.
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OBJECTIVES: We sought to examine the frequency of depression after small vessel-type stroke (SVS) and associated risk factors. MATERIALS AND METHODS: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the American Stroke Association-Bugher SVS Study, which included 200 participants within 2-years of SVS and 79 controls without a history of stroke from 2007 to 2012 at four sites. The primary outcome was PHQ-8, with scores ≥10 consistent with post-stroke depression (PSD). A logistic regression adjusted for age, race, sex, history of diabetes and Short-Form Montreal Cognitive Assessment score (SF-MoCA) was used to compare the risk of having depression after SVS compared to controls. Another logistic regression, adjusted for age, sex, race, level of education, SF-MoCA, white matter disease (WMD) burden, stroke severity (NIHSS), time between stroke and depression screen, history of diabetes, and history of hypertension was used to identify factors independently associated with depression in participants with SVS. RESULTS: The cohort included 161 participants with SVS (39 excluded due to missing data) and 79 controls. The mean interval between stroke and depression screening was 74 days. Among participants with SVS, 31.7% (n = 51) had PSD compared to 6.3% (n = 5) of controls (RR = 5.44, 95% CI = 2.21-13.38, p = 0.0002). The only two variables independently associated with PSD in participants with SVS were female sex (RR = 1.84, 95% CI = 1.09-3.09, p = 0.020) and diabetes (RR 1.69, 95% CI 1.03-2.79). CONCLUSIONS: After adjusting for several demographic and clinical variables, having a SVS was associated with an approximate 5-fold increased risk of depression and was more frequent in women and in those with diabetes. The extent of WMD was not independently associated with PSD, suggesting that small vessel disease in the setting of an overt SVS may not account for the increased prevalence of depression.
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Diabetes Mellitus , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologíaRESUMEN
BACKGROUND: White matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease. OBJECTIVE: Conducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol. METHODS: The NINDS-supported MarkVCID Consortium evaluated a neuroimaging biomarker developed to track WMH change. Test-retest and cross-site inter-rater reliability of the protocol were assessed. Cognitive test scores were analyzed in relation to WMH changes to explore its construct validity. RESULTS: ICC values for test-retest reliability of WMH growth and regression were 0.969 and 0.937 respectively, while for cross-site inter-rater ICC values for WMH growth and regression were 0.995 and 0.990 respectively. Word list long-delay free-recall was negatively associated with WMH growth (p < 0.028) but was not associated with WMH regression. CONCLUSIONS: The present data demonstrate robust ICC validity of a WMH growth/regression protocol over a one-year period as measured by cross-site inter-rater and test-retest reliability. These data suggest that this approach may serve an important role in clinical trials of disease-modifying agents for VCID that may preferentially affect WMH growth, stability, or regression.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia Vascular , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética , Enfermedad de Alzheimer/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , BiomarcadoresRESUMEN
BACKGROUND: Medicaid serves as a safety net for low-income US Medicare beneficiaries with limited assets. Approximately 7.7 million Americans aged ≥65 years rely on a combination of Medicare and Medicaid to obtain critical medical services, yet little is known about whether these patients have worse outcomes after stroke than patients with Medicare alone. We compared geographic patterns in dual Medicare-Medicaid eligibility and ischemic stroke hospitalizations and examined whether these dual-eligible beneficiaries had worse post-stroke outcomes than those with Medicare alone. METHODS: We identified fee-for-service Medicare beneficiaries aged ≥65 years who were discharged from US acute-care hospitals with a principal diagnosis of ischemic stroke in 2014. Medicare beneficiaries with ≥1 month of Medicaid coverage were considered dual eligible. We mapped risk-standardized stroke hospitalization rates and percentages of beneficiaries with dual eligibility. Mixed models and Cox regression were used to evaluate relationships between dual-eligible status and outcomes up to 1 year after stroke, adjusting for demographic and clinical factors. RESULTS: At the national level, 12.5% of beneficiaries were dual eligible. Dual-eligible rates were highest in Maine, Alaska, and the southern half of the United States, whereas stroke hospitalization rates were highest in the South and parts of the Midwest (Pearson's r = 0.469, p<0.001). Among 254,902 patients hospitalized for stroke, 17.4% were dual eligible. In adjusted analyses, dual-eligible patients had greater risk of all-cause readmission within 30 days (hazard ratio 1.06, 95% confidence interval [CI] 1.03-1.09) and 1 year (hazard ratio 1.03, 95% CI 1.02-1.05) and had greater odds of death within 1 year (odds ratio 1.20, 95% CI 1.17-1.23) when compared with Medicare-only patients; there was no difference in in-hospital or 30-day mortality. CONCLUSION: Dual-eligible stroke patients had higher readmissions and long-term mortality than other patients, even after comorbidity adjustment. A better understanding of the factors contributing to these poorer outcomes is needed.
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Accidente Cerebrovascular Isquémico , Medicare , Humanos , Anciano , Estados Unidos/epidemiología , Medicaid , Hospitalización , AlaskaRESUMEN
The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.
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Anticolesterolemiantes , Demencia , Accidente Cerebrovascular Hemorrágico , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Accidente Cerebrovascular , Humanos , American Heart Association , Anticolesterolemiantes/efectos adversos , Encéfalo , LDL-Colesterol , Demencia/diagnóstico , Demencia/epidemiología , Demencia/prevención & control , Ezetimiba , Accidente Cerebrovascular Hemorrágico/diagnóstico , Accidente Cerebrovascular Hemorrágico/epidemiología , Accidente Cerebrovascular Hemorrágico/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: Whether stroke patients treated at hospitals with better short-term outcome metrics have better long-term outcomes is unknown. We investigated whether treatment at US hospitals with better 30-day hospital-level stroke outcome metrics was associated with better 1-year outcomes, including reduced mortality and recurrent stroke, for patients after ischemic stroke. METHODS: This cohort study included Medicare fee-for-service beneficiaries aged ≥65 years discharged alive from US hospitals with a principal diagnosis of ischemic stroke from 07/01/2015 to 12/31/2018. We categorized patients by the treating hospital's performance on the CMS hospital-specific 30-day risk-standardized all-cause mortality and readmission measures for ischemic stroke from 07/01/2012 to 06/30/2015: Low-Low (both CMS mortality and readmission rates for the hospital were <25th percentile of national rates), High-High (both >75th percentile), and Intermediate (all other hospitals). We balanced characteristics between hospital performance categories using stabilized inverse probability weights (IPW) based on patient demographic and clinical factors. We fit Cox models assessing patient risks of 1-year all-cause mortality and ischemic stroke recurrence across hospital performance categories, weighted by the IPW and accounting for competing risks. RESULTS: There were 595,929 stroke patients (mean age 78.9±8.8 years, 54.4% women) discharged from 2,563 hospitals (134 Low-Low, 2288 Intermediate, 141 High-High). For Low-Low, Intermediate, and High-High hospitals, respectively, 1-year mortality rates were 23.8% (95% confidence interval [CI] 23.3%-24.3%), 25.2% (25.1%-25.3%), and 26.5% (26.1%-26.9%), and recurrence rates were 8.0% (7.6%-8.3%), 7.9% (7.8%-8.0%), and 8.0% (7.7%-8.3%). Compared with patients treated at High-High hospitals, those treated at Low-Low and Intermediate hospitals, respectively, had 15% (hazard ratio 0.85; 95% CI 0.82-0.87) and 9% (0.91; 0.89-0.93) lower risks of 1-year mortality but no difference in recurrence. CONCLUSIONS: Ischemic stroke patients treated at hospitals with better CMS short-term outcome metrics had lower risks of post-discharge 1-year mortality, but similar recurrent stroke rates, compared with patients treated at other hospitals.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Anciano , Femenino , Estados Unidos/epidemiología , Anciano de 80 o más Años , Masculino , Medicare , Estudios de Cohortes , Benchmarking , Cuidados Posteriores , Readmisión del Paciente , Alta del Paciente , Accidente Cerebrovascular/diagnóstico , Hospitales , Infarto CerebralRESUMEN
BACKGROUND AND PURPOSE: Human amylin is a 37 amino-acid pancreatic peptide that forms neuro-toxic aggregates that deposit in the endothelium of brain capillaries of patients with diabetes, potentially contributing to cerebral small vessel ischemic injury. Pathogenic amylin also deposits in the capillary endothelium in other organs, including the skin. The aim of this study was to test the hypothesis that skin capillary amylin deposition correlates with cerebral small vessel amylin deposition, potentially providing a clinically useful marker of cerebral amylin deposition. METHODS: Immunohistochemistry (IHC) was performed for human amylin and collagen IV in brain and skin sections of rats (age 15-16 months) with pancreatic overexpression of amyloidogenic human amylin polypeptide (HIP rats), and control rats (Wild type; WT; rats that express non-amyloidogenic rat amylin) using antibodies binding amylin (n = 5 male and 5 female rats for each group) and antibodies binding Hypoxia inducing factor (HIF)-1α and HIF-2α (n = 3 for each group). The reactive amylin-aldehyde 4-hydroxynonenal (4-HNE) adduct was measured in skin homogenates. (n = 4 for each group) RESULTS: Brain capillaries isolated from HIP rats had higher amylin content compared to WT rats using Western blot with anti-amylin antibody (p = 0.0010). The HIF-1α and HIF-2α immunoreactivity signals in skin from HIP and WT rats were similar (p = 0.2 for HIF-1 α, and p = 0.75 for HIF-2α). Amylin-4HNE adduct formation was higher in HIP rats compared to WT rats (p = 0.0014). There was phenotypic similarity between brain and skin capillary amylin based on co-staining for human amylin and collagen IV in both HIP and WT rats. CONCLUSION: Skin and brain capillary amylin deposition are similar providing evidence that a skin biopsy might be providing a potential biomarker for diabetes-associated intracranial vasculopathy.
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Capilares , Polipéptido Amiloide de los Islotes Pancreáticos , Ratas , Humanos , Masculino , Animales , Femenino , Lactante , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Capilares/metabolismo , Encéfalo/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Colágeno/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent ICH), IS, and recurrent ICH associated with statin use among ICH survivors. METHODS: Using the Danish Stroke Registry, we identified all patients admitted to a hospital in Denmark (population 5.8 million) with a first-ever ICH between January 2003 and December 2021 who were aged 50 years or older and survived >30 days. Patients were followed up until August 2022. Within this cohort, we conducted 3 nested case-control analyses for any stroke, IS, and recurrent ICH. We matched controls for age, sex, time since first-ever ICH, and history of prior IS. The primary exposure was statin use before or on the date of subsequent stroke or the equivalent date in matched controls. Using conditional logistic regression, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for any stroke, IS, and recurrent ICH associated with statin exposure. RESULTS: We identified 1,959 patients with any stroke (women 45.3%; mean [SD] age, 72.6 [9.7] years) who were matched to 7,400 controls; 1,073 patients with IS (women 42.0%; mean [SD] age, 72.4 [10.0] years) who were matched to 4,035 controls and 984 patients with recurrent ICH (women 48.7%; mean [SD] age, 72.7 [9.2] years) who were matched to 3,755 controls. Statin exposure was associated with a lower risk of both any stroke (cases 38.6%, controls 41.1%; aOR 0.88; 95% CI 0.78-0.99) and IS (cases 39.8%, controls 41.8%, aOR 0.79; 95% CI 0.67-0.92), but was not associated with recurrent ICH risk (cases 39.1%, controls 40.8%, aOR 1.05; 95% CI 0.88-1.24). DISCUSSION: Exposure to statins was not associated with an increased risk of recurrent ICH but was associated with a lower risk of any stroke, largely due to a lower risk of IS. Confirmation of these findings in randomized trials is needed. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that statin use in patients with ICH is associated with a lower risk of any stroke and IS and not with increased risk of recurrent ICH.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/inducido químicamente , Hemorragia Cerebral/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Modelos LogísticosRESUMEN
BACKGROUND: Little is known about the characteristics and determinants of post-stroke cognitive impairment in residents of low- and middle-income countries. The objective of this study was to determine the frequencies, patterns, and risk factors for cognitive impairment in a cross-sectional study of consecutive stroke patients cared for at Uganda's Mulago Hospital, located in sub-Saharan Africa. METHODS: 131 patients were enrolled a minimum of 3-months after hospital admission for stroke. A questionnaire, clinical examination findings, and laboratory test results were used to collect demographic information and data on vascular risk factors and clinical characteristics. Independent predictor variables associated with cognitive impairment were ascertained. Stroke impairments, disability, and handicap were assessed using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin scale (mRS), respectively. The Montreal Cognitive Assessment (MoCA) was used to assess participants' cognitive function. Stepwise multiple logistic regression was used to identify variables independently associated with cognitive impairment. RESULTS: The overall mean MoCA score was 11.7-points (range 0.0-28.0-points) for 128 patients with available data of whom 66.4% were categorized as cognitively impaired (MoCA < 19-points). Increasing age (OR 1.04, 95% CI 1.00-1.07; p = 0.026), low level of education (OR 3.23, 95% CI 1.25-8.33; p = 0.016), functional handicap (mRS 3-5; OR 1.84, 95% CI 1.28-2.63; p < 0.001) and high LDL cholesterol (OR 2.74, 95% CI 1.14-6.56; p = 0.024) were independently associated with cognitive impairment. CONCLUSIONS: Our findings highlight the high burden and need for awareness of cognitive impairment in post stroke populations in the sub-Saharan region and serve to emphasize the importance of detailed cognitive assessment as part of routine clinical evaluation of patients who have had a stroke.
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Disfunción Cognitiva , Accidente Cerebrovascular , Humanos , Prevalencia , Uganda/epidemiología , Estudios Transversales , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Sobrevivientes , Pruebas NeuropsicológicasRESUMEN
Importance: Survivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing the risk of MACEs according to index hematoma location. Objective: To examine the risk of MACEs (ie, the composite of ICH, IS, spontaneous intracranial extra-axial hemorrhage, MI, systemic embolism, or vascular death) after ICH based on ICH location (lobar vs nonlobar). Design, Setting, and Participants: This cohort study identified 2819 patients in southern Denmark (population of 1.2 million) 50 years or older hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018. Intracerebral hemorrhage was categorized as lobar or nonlobar, and the cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs and separately recurrent ICH, IS, and MI. Outcome events were validated using medical records. Associations were adjusted for potential confounders using inverse probability weighting. Exposure: Location of ICH (lobar vs nonlobar). Main Outcomes and Measures: The main outcomes were MACEs and separately recurrent ICH, IS, and MI. Crude absolute event rates per 100 person-years and adjusted hazard ratios (aHRs) with 95% CIs were calculated. Data were analyzed from February to September 2022. Results: Compared with patients with nonlobar ICH (n = 1255; 680 [54.2%] men and 575 [45.8%] women; mean [SD] age, 73.5 [11.4] years), those with lobar ICH (n = 1034; 495 [47.9%] men and 539 [52.1%] women, mean [SD] age, 75.2 [10.7] years) had higher rates of MACEs per 100 person-years (10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; aHR, 1.26; 95% CI, 1.10-1.44) and recurrent ICH (3.74 [95% CI, 3.01-4.66] vs 1.24 [95% CI, 0.89-1.73]; aHR, 2.63; 95% CI, 1.97-3.49) but not IS (1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) or MI (0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09). Conclusions and Relevance: In this cohort study, spontaneous lobar ICH was associated with a higher rate of subsequent MACEs than nonlobar ICH, primarily due to a higher rate of recurrent ICH. This study highlights the importance of secondary ICH prevention strategies in patients with lobar ICH.
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Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Masculino , Humanos , Femenino , Anciano , Estudios de Cohortes , Hemorragia Cerebral/epidemiología , Hemorragias Intracraneales/complicaciones , Hematoma , Accidente Cerebrovascular Isquémico/complicaciones , Infarto del Miocardio/complicacionesRESUMEN
Islet amyloid polypeptide (amylin) secreted from the pancreas crosses from the blood to the brain parenchyma and forms cerebral mixed amylin-ß amyloid (Aß) plaques in persons with Alzheimer's disease (AD). Cerebral amylin-Aß plaques are found in both sporadic and early-onset familial AD; however, the role of amylin-Aß co-aggregation in potential mechanisms underlying this association remains unknown, in part due to lack of assays for detection of these complexes. Here, we report the development of an ELISA to detect amylin-Aß hetero-oligomers in brain tissue and blood. The amylin-Aß ELISA relies on a monoclonal anti-Aß mid-domain antibody (detection) and a polyclonal anti-amylin antibody (capture) designed to recognize an epitope that is distinct from the high affinity amylin-Aß binding sites. The utility of this assay is supported by the analysis of molecular amylin-Aß codeposition in postmortem brain tissue obtained from persons with and without AD pathology. By using transgenic AD-model rats, we show that this new assay can detect circulating amylin-Aß hetero-oligomers in the blood and is sensitive to their dissociation to monomers. This is important because therapeutic strategies to block amylin-Aß co-aggregation could reduce or delay the development and progression of AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Encéfalo , Animales , Ratones , Ratas , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Ratones Transgénicos , Páncreas/metabolismo , Ratas TransgénicasRESUMEN
Acute atrial fibrillation is defined as atrial fibrillation detected in the setting of acute care or acute illness; atrial fibrillation may be detected or managed for the first time during acute hospitalization for another condition. Atrial fibrillation after cardiothoracic surgery is a distinct type of acute atrial fibrillation. Acute atrial fibrillation is associated with high risk of long-term atrial fibrillation recurrence, warranting clinical attention during acute hospitalization and over long-term follow-up. A framework of substrates and triggers can be useful for evaluating and managing acute atrial fibrillation. Acute management requires a multipronged approach with interdisciplinary care collaboration, tailoring treatments to the patient's underlying substrate and acute condition. Key components of acute management include identification and treatment of triggers, selection and implementation of rate/rhythm control, and management of anticoagulation. Acute rate or rhythm control strategy should be individualized with consideration of the patient's capacity to tolerate rapid rates or atrioventricular dyssynchrony, and the patient's ability to tolerate the risk of the therapeutic strategy. Given the high risks of atrial fibrillation recurrence in patients with acute atrial fibrillation, clinical follow-up and heart rhythm monitoring are warranted. Long-term management is guided by patient substrate, with implications for intensity of heart rhythm monitoring, anticoagulation, and considerations for rhythm management strategies. Overall management of acute atrial fibrillation addresses substrates and triggers. The 3As of acute management are acute triggers, atrial fibrillation rate/rhythm management, and anticoagulation. The 2As and 2Ms of long-term management include monitoring of heart rhythm and modification of lifestyle and risk factors, in addition to considerations for atrial fibrillation rate/rhythm management and anticoagulation. Several gaps in knowledge related to acute atrial fibrillation exist and warrant future research.
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Fibrilación Atrial , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , American Heart Association , Antiarrítmicos/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Hospitalización , Frecuencia CardíacaRESUMEN
BACKGROUND AND OBJECTIVES: A causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations. METHODS: We conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population 1.2 million), we identified all first-ever cases of ICH between 2009 and 2018 in persons aged ≥55 years. Patients with medical record-verified diagnoses were classified as having a lobar or nonlobar ICH and matched for age, sex, and calendar year to general population controls. We used a nationwide prescription registry to ascertain prior statin and other medication use that we classified for recency, duration, and intensity. Using conditional logistic regression adjusted for potential confounders, we calculated adjusted ORs (aORs) and corresponding 95% CIs for the risk of lobar and nonlobar ICH. RESULTS: We identified 989 patients with lobar ICH (52.2% women, mean age 76.3 years) who we matched to 39,500 controls and 1,175 patients with nonlobar ICH (46.5% women, mean age 75.1 years) who we matched to 46,755 controls. Current statin use was associated with a lower risk of lobar (aOR 0.83; 95% CI, 0.70-0.98) and nonlobar ICH (aOR 0.84; 95% CI, 0.72-0.98). Longer duration of statin use was also associated with a lower risk of lobar (<1 year: aOR 0.89; 95% CI, 0.69-1.14; ≥1 year to <5 years aOR 0.89; 95% CI 0.73-1.09; ≥5 years aOR 0.67; 95% CI, 0.51-0.87; p for trend 0.040) and nonlobar ICH (<1 year: aOR 1.00; 95% CI, 0.80-1.25; ≥1 year to <5 years aOR 0.88; 95% CI 0.73-1.06; ≥5 years aOR 0.62; 95% CI, 0.48-0.80; p for trend <0.001). Estimates stratified by statin intensity were similar to the main estimates for low-medium intensity therapy (lobar aOR 0.82; nonlobar aOR 0.84); the association with high-intensity therapy was neutral. DISCUSSION: We found that statin use was associated with a lower risk of ICH, particularly with longer treatment duration. This association did not vary by hematoma location.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Anciano , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Sistema de Registros , Estudios de Casos y Controles , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/epidemiología , Duración de la TerapiaRESUMEN
BACKGROUND: Long-term exposure to air pollutants is associated with increased stroke incidence, morbidity, and mortality; however, research on the association of pollutant exposure with poststroke hospital readmissions is lacking. METHODS: We assessed associations between average annual carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matter 2.5, and sulfur dioxide (SO2) exposure and 30-day all-cause hospital readmission in US fee-for-service Medicare beneficiaries age ≥65 years hospitalized for ischemic stroke in 2014 to 2015. We fit Cox models to assess 30-day readmissions as a function of these pollutants, adjusted for patient and hospital characteristics and ambient temperature. Analyses were then stratified by treating hospital performance on the Centers for Medicare and Medicaid Services risk-standardized 30-day poststroke all-cause readmission measure to determine if the results were independent of performance: low (Centers for Medicare and Medicaid Services rate for hospital <25th percentile of national rate), high (>75th percentile), and intermediate (all others). RESULTS: Of 448 148 patients with stroke, 12.5% were readmitted within 30 days. Except for tropospheric NO2 (no national standard), average 2-year CO, O3, particulate matter 2.5, and SO2 values were below national limits. Each one SD increase in average annual CO, NO2, particulate matter 2.5, and SO2 exposure was associated with an adjusted 1.1% (95% CI, 0.4-1.9%), 3.6% (95% CI, 2.9%-4.4%), 1.2% (95% CI, 0.2%-2.3%), and 2.0% (95% CI, 1.1%-3.0%) increased risk of 30-day readmission, respectively, and O3 with a 0.7% (95% CI, 0.0%-1.5%) decrease. Associations between long-term air pollutant exposure and increased readmissions persisted across hospital performance categories. CONCLUSIONS: Long-term air pollutant exposure below national limits was associated with increased 30-day readmissions after stroke, regardless of hospital performance category. Whether air quality improvements lead to reductions in poststroke readmissions requires further research.
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Contaminantes Atmosféricos , Contaminación del Aire , Accidente Cerebrovascular , Estados Unidos/epidemiología , Humanos , Anciano , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Readmisión del Paciente , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Dióxido de Nitrógeno/análisis , Medicare , Material Particulado/efectos adversos , Material Particulado/análisis , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
Impairment of vascular pathways of cerebral ß-amyloid (Aß) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral Aß clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with Aß within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-Aß co-deposits. LRP1-mediated Aß transport across the blood-brain barrier and Aß clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by Aß deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and Aß pathology.
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Enfermedad de Alzheimer , Polipéptido Amiloide de los Islotes Pancreáticos , Humanos , Ratas , Animales , Polipéptido Amiloide de los Islotes Pancreáticos/genética , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas Amiloidogénicas , Páncreas/metabolismo , InflamaciónRESUMEN
Background Little is known about the characteristics and determinants of post-stroke cognitive impairments in low- and middle-income countries. The objective of this study was to determine the frequencies, patterns, and risk factors for cognitive impairment in a cross-sectional study of consecutive stroke patients cared for at Uganda's Mulago Hospital, located in sub-Saharan Africa. Methods From August 2019 to July 2020, patients were enrolled a minimum of 3-months post-stroke hospital admission. We collected data on their demographics, vascular risk factors and clinical factors using a questionnaire, clinical examination findings, and test results. Independent predictor variables associated with cognitive impairment were ascertained. Stroke impairments, disability, and handicap were assessed using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin scale (mRS), respectively. The Montreal Cognitive Assessment (MoCA) was used to assess participants' cognitive function. Stepwise multiple logistic regression was used to identify variables independently associated with cognitive impairment. Results The overall mean MoCA score was 11.7-points (range 0.0-28.0-points) for 128 patients with available data of whom 66.4% were categorized as cognitively impaired (MoCA < 19-points). Increasing age (OR 1.04, 95% CI 1.00-1.07; p = 0.026), low level of education (OR 3.23, 95% CI 1.25-8.33; p = 0.016), functional handicap (mRS 3-5; OR 1.84, 95% CI 1.28-2.63; p < 0.001) and high LDL cholesterol (OR 2.74, 95% CI 1.14-6.56; p = 0.024) were independently associated with cognitive impairment. Discussion Further longitudinal, prospective studies are required to confirm these findings and identify strategies for reducing the risk of post-stroke cognitive impairment in this population.