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2.
J Clin Neurosci ; 123: 173-178, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583373

RESUMO

Racial-ethnic disparities exist in the prevalence and outcomes of heart failure (HF) and are presumed to be related to differences in cardiovascular risk factor burden and control. There is little data on stroke disparities among patients with HF or the factors responsible. We hypothesized disparities in stroke prevalence exist among patients with HF in a manner not fully explained by burden of cardiovascular disease. We analyzed data from the National Health and Nutrition Examination Survey (1999-2014). Cardiovascular profiles were compared by race/ethnicity. Using survey-weighted models, effect modification of the relationship between HF and stroke by race/ethnicity was examined adjusting for cardiovascular profiles. Of 40,437 participants, 2.5 % had HF. The HF cohort had a greater proportion of White and Black participants (77 % vs 74 % and 15 % vs 12 %, respectively) and fewer participants of Hispanic ethnicity (8 % vs 14 %). Stroke was 8 times more prevalent in HF (19.6 % vs 2.3 %, <0.001). Among individuals with HF, race-ethnic differences were identified in the prevalence and mean values of vascular risk factors but were largely driven by higher rates in Black participants. There was significant interaction between HF and race/ethnicity; HF increased the odds of stroke over 7-fold in participants of Hispanic ethnicity (aOR: 7.84; 95 % CI: 4.11-15.0) but to a lesser extent in Black and White participants (Black aOR: 2.49; 95 % CI: 1.72-3.60; White aOR: 3.36; 95 % CI: 2.57-4.40). People of Hispanic ethnicity with HF have a disproportionately higher risk of stroke in a manner not fully explained by differences in vascular risk profiles.

3.
Nat Rev Cardiol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509244

RESUMO

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

4.
Semin Thromb Hemost ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428841

RESUMO

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

5.
Circulation ; 149(12): e964-e985, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38344851

RESUMO

In 1924, the founders of the American Heart Association (AHA) envisioned an international society focused on the heart and aimed at facilitating research, disseminating information, increasing public awareness, and developing public health policy related to heart disease. This presidential advisory provides a comprehensive review of the past century of cardiovascular and stroke science, with a focus on the AHA's contributions, as well as informed speculation about the future of cardiovascular science into the next century of the organization's history. The AHA is a leader in fundamental, translational, clinical, and population science, and it promotes the concept of the "learning health system," in which a continuous cycle of evidence-based practice leads to practice-based evidence, permitting an iterative refinement in clinical evidence and care. This advisory presents the AHA's journey over the past century from instituting professional membership to establishing extraordinary research funding programs; translating evidence to practice through clinical practice guidelines; affecting systems of care through quality programs, certification, and implementation; leading important advocacy efforts at the federal, state and local levels; and building global coalitions around cardiovascular and stroke science and public health. Recognizing an exciting potential future for science and medicine, the advisory offers a vision for even greater impact for the AHA's second century in its continued mission to be a relentless force for longer, healthier lives.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Acidente Vascular Cerebral , Estados Unidos , Humanos , American Heart Association , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/epidemiologia , Prática Clínica Baseada em Evidências , Mediastino , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/epidemiologia
6.
JAMA ; 331(7): 573-581, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38324415

RESUMO

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.


Assuntos
Fibrilação Atrial , Cardiopatias , AVC Isquêmico , Pirazóis , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Método Duplo-Cego , Canadá , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Aspirina/efeitos adversos , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Cardiopatias/complicações , AVC Isquêmico/tratamento farmacológico , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Hemorragias Intracranianas/induzido quimicamente
7.
Nat Commun ; 15(1): 1492, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374032

RESUMO

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Adulto , Humanos , Feminino , Masculino , Idoso , Formação de Anticorpos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Demografia , Vacinação
8.
Alzheimers Dement ; 20(4): 2497-2507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38332543

RESUMO

INTRODUCTION: We tested the association of brain artery diameters with dementia and stroke risk in three distinct population-based studies using conventional T2-weighted brain magnetic resonance imaging (MRI) images. METHODS: We included 8420 adults > 40 years old from three longitudinal population-based studies with brain MRI scans. We estimated and meta-analyzed the hazard ratios (HRs) of the brain and carotids and basilar diameters associated with dementia and stroke. RESULT: Overall and carotid artery diameters > 95th percentile increased the risk for dementia by 1.74 (95% confidence interval [CI], 1.13-2.68) and 1.48 (95% CI, 1.12-1.96) fold, respectively. For stroke, meta-analyses yielded HRs of 1.59 (95% CI, 1.04-2.42) for overall arteries and 2.11 (95% CI, 1.45-3.08) for basilar artery diameters > 95th percentile. DISCUSSION: Individuals with dilated brain arteries are at higher risk for dementia and stroke, across distinct populations. Our findings underline the potential value of T2-weighted brain MRI-based brain diameter assessment in estimating the risk of dementia and stroke.


Assuntos
Demência , Acidente Vascular Cerebral , Adulto , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicações , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Artéria Basilar , Demência/diagnóstico por imagem , Demência/epidemiologia , Demência/complicações , Fatores de Risco
10.
Inflamm Bowel Dis ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271615

RESUMO

BACKGROUND: Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders. METHODS: We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model. RESULTS: In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy. CONCLUSIONS: Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance.


This systematic review and meta-analysis of cohort studies aimed to clarify association between inflammatory bowel disease and risks of common neurological disorders. Based on analyses, inflammatory bowel disease may modestly increase risks of stroke, all-cause dementia, and Parkinson's disease vs the healthy population.

11.
Circulation ; 149(8): e347-e913, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38264914

RESUMO

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Acidente Vascular Cerebral , Humanos , Estados Unidos/epidemiologia , American Heart Association , Cardiopatias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Obesidade/epidemiologia
12.
J Am Coll Cardiol ; 83(3): 444-465, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38233019

RESUMO

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.


Assuntos
Fibrilação Atrial , Trombose , Tromboembolia Venosa , Trombose Venosa , Humanos , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Vitamina K , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Neurology ; 102(2): e207961, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38165319

RESUMO

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. METHODS: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. RESULTS: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient ß = 0.020; SE = 0.009; p = 0.03). DISCUSSION: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.


Assuntos
AVC Isquêmico , Noma , Acidente Vascular Cerebral Lacunar , Acidente Vascular Cerebral , Idoso , Humanos , Estudos Transversais , Hematócrito , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Pessoa de Meia-Idade
14.
Atherosclerosis ; 390: 117456, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262274

RESUMO

BACKGROUND AND AIMS: Information on the association between dietary oily fish intake and intracranial atherosclerosis is limited and contradictory. Inconsistencies might be in part related to heterogeneous designs and differences in race/ethnicity of study populations. We aim to assess whether oily fish intake is inversely associated with intracranial artery stenosis (ICAS) in frequent fish consumers of indigenous ancestry living in coastal Ecuador. METHODS: The study included 384 participants aged ≥60 years enrolled in the Atahualpa Project Cohort. Dietary oily fish intake was quantified systematically via validated surveys and all participants received a time-of-flight MRA of intracranial vessels. Poisson regression models, adjusted for demographics, level of education, traditional risk factors and severe tooth loss, were fitted to assess the association between amounts of oily fish intake and the number of intracranial arteries with moderate-to-severe (≥50 %) stenosis. RESULTS: Participants had a mean age of 67.7 ± 7 years, and 56 % were women. The mean oily fish intake was 8.9 ± 5.2 servings/week; 283 (74 %) participants consumed ≥5.2 servings/week (2nd to 4th quartiles of fish intake). Forty-three (11 %) participants had at least one major intracranial artery with moderate-to-severe stenosis. Both univariate and multivariate models showed a significant inverse association between consumption of oily fish in the 2nd to 4th quartiles and ≥50 % stenosis in at least one artery (ß: 0.46; 95 % C.I.: 0.27-077, and ß: 0.52; 95 % C.I.: 0.30-0.90, respectively). CONCLUSIONS: Consumption of more than five oily fish servings/week is associated with lower prevalence of moderate-to-severe ICAS in indigenous Ecuadorians.


Assuntos
Dieta , População da América do Sul , Animais , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Equador/epidemiologia , Constrição Patológica , Fatores de Risco
15.
Stroke ; 55(1): 69-77, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38063018

RESUMO

BACKGROUND: Aortic arch plaques are associated with an increased risk of ischemic stroke in patients with cryptogenic stroke or prior embolic events. However, this relationship is unclear in the community. We investigated (1) the long-term risk of stroke and cardiovascular events associated with arch plaques and (2) whether statin therapy prescribed for any indication modified the association. METHODS: A total of 934 stroke-free participants (72±9 years; 37% men) from the CABL study (Cardiovascular Abnormalities and Brain Lesion) were evaluated. Arch plaques were assessed by suprasternal transthoracic echocardiography; plaques ≥4 mm in thickness were classified as large plaques. The primary outcome was ischemic stroke; the secondary outcome was combined cardiovascular events (ischemic stroke, myocardial infarction, and cardiovascular death). The plaque-related risk of outcomes was also analyzed according to the presence of statin treatment. No plaque was used as a reference. RESULTS: Aortic arch plaques were present in 645 participants (69.1%), with large plaques in 114 (12.2%). During a mean follow-up of 11.3±3.6 years, 236 (25.3%) cardiovascular events occurred (76 ischemic strokes, 27 myocardial infarctions, and 133 cardiovascular deaths). Large arch plaques were independently associated with combined events (adjusted hazard ratio, 2.19 [95% CI, 1.40-3.43]) but not stroke alone (adjusted hazard ratio, 1.09 [95% CI, 0.50-2.38]). The association between large plaques and cardiovascular events was significant in participants receiving statins (adjusted hazard ratio, 2.57 [95% CI, 1.52-4.37]) but not in others; however, participants on statin treatment also had a worse risk profile (higher body mass index, greater frequencies of hypertension, diabetes, and coronary artery disease). CONCLUSIONS: Aortic arch plaques may be a marker of cardiovascular risk rather than a direct embolic stroke source in older adults without prior stroke. The efficacy of broader cardiovascular risk factors control, beyond cholesterol levels alone, for primary prevention of cardiovascular events in individuals with aortic arch plaques may require further investigation.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Infarto do Miocárdio , Placa Aterosclerótica , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aorta Torácica/diagnóstico por imagem , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/complicações , AVC Isquêmico/complicações
16.
Ann Neurol ; 95(2): 325-337, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37787451

RESUMO

OBJECTIVE: Genome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. METHODS: A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired-end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. RESULTS: Common and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired-end tag data analysis highlighted the presence of long-range interactions between the SEMA4A-promoter and PMF1-enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. INTERPRETATION: Altered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325-337.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Semaforinas , Acidente Vascular Cerebral Lacunar , Humanos , Estudo de Associação Genômica Ampla , Hemorragia Cerebral/genética , Hemorragia Cerebral/complicações , Doenças de Pequenos Vasos Cerebrais/genética , Doenças de Pequenos Vasos Cerebrais/complicações , Acidente Vascular Cerebral Lacunar/complicações , Cromatina , Semaforinas/genética
17.
Stroke ; 55(1): 236-247, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38134261

RESUMO

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features. We also comment on breakthrough developments in patient selection algorithms for PFO closure in relation to the PFO-associated stroke causal likelihood risk stratification system. We further highlight areas for future research in PFO-associated stroke including the efficacy and safety of PFO closure in the elderly population, incidence, and long-term consequences of atrial fibrillation post-PFO closure, generalizability of the results of clinical trials in the real world, and the need for assessing the effect of neurocardiology teams on adherence to international recommendations. Other important knowledge gaps such as sex, race/ethnicity, and regional disparities in access to diagnostic technologies, PFO closure devices, and clinical outcomes in the real world are also discussed as priority research topics.


Assuntos
Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Idoso , Forame Oval Patente/complicações , Forame Oval Patente/epidemiologia , Forame Oval Patente/cirurgia , Resultado do Tratamento , Recidiva Local de Neoplasia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico , Fatores de Risco , AVC Isquêmico/complicações , Prevenção Secundária/métodos , Recidiva , Cateterismo Cardíaco
18.
J Neurol Sci ; 454: 120856, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37913646

RESUMO

Prior work in the Northern Manhattan Study (NOMAS) identified impaired cognition in cross-sectional analyses and more rapid memory decline in individuals with evidence of prior common infectious disease exposures. In this study, we sought to determine the cross-sectional relationship between prior exposure to cytomegalovirus, herpes simplex viruses 1 and 2, Chlamydia pneumoniae, and Helicobacter pylori and three magnetic resonance imaging (MRI) signatures (whole-brain cortical thickness, a previously validated AD signature, and hippocampal volume) in 455 NOMAS participants. We performed confounder-adjusted linear regression analyses between neuroimaging scores and both continuous serologies and categorical seropositivity of each pathogen, as well as a combined infectious burden index (IBI). We identified that increased serologic titers of herpes simplex virus 2 were associated with reduced whole-brain cortical thickness, and a combined score of HSV-2 and C. pneumoniae displayed an additive effect on reduced cortical thickness. Our findings suggest herpes simplex virus 2 seropositivity may contribute to accelerated brain aging, possibly resulting in an increased vulnerability to cognitive impairment and neurodegenerative disease in aging populations.


Assuntos
Doença de Alzheimer , Herpes Simples , Doenças Neurodegenerativas , Noma , Humanos , Idoso , Herpesvirus Humano 2 , Doenças Neurodegenerativas/complicações , Vida Independente , Noma/complicações , Encéfalo , Herpes Simples/complicações , Herpes Simples/diagnóstico por imagem , Doença de Alzheimer/complicações
19.
Appl Clin Inform ; 14(5): 883-891, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37940129

RESUMO

BACKGROUND: Inequities in health care access leads to suboptimal medication adherence and blood pressure (BP) control. Informatics-based approaches may deliver equitable care and enhance self-management. Patient-reported outcomes (PROs) complement clinical measures to assess the impact of illness on patients' well-being in poststroke care. OBJECTIVES: The aim of this study was to determine the feasibility of incorporating PROs into Telehealth After Stroke Care (TASC) and to explore the effect of this team-based remote BP monitoring program on psychological distress and quality of life in an underserved urban setting. METHODS: Patients discharged home from a Comprehensive Stroke Center were randomized to TASC or usual care for 3 months. They were provided with a BP monitor and a tablet that wirelessly transmitted data to a cloud-based platform, which were integrated with the electronic health record. Participants who did not complete the tablet surveys were contacted via telephone or e-mail. We collected the Patient-Reported Outcomes Measurement Information System Managing Medications and Treatment (PROMIS-MMT), Patient Activation Measure (PAM), Neuro-QOL (Quality of Life in Neurological Disorders) Cognitive Function, Neuro-QOL Depression, and Patient Health Questionnaire-9 (PHQ-9). T-tests and linear regression were used to evaluate the differences in PRO change between the arms. RESULTS: Of the 50 participants, two-thirds were Hispanic or non-Hispanic Black individuals. Mechanisms of PRO submission for the arms included tablet (62 vs. 47%), phone (24 vs. 37%), tablet with phone coaching (10 vs. 16%), and e-mail (4 vs. 0%). PHQ-9 depressive scores were nominally lower in TASC at 3 months compared with usual care (2.7 ± 3.6 vs. 4.0 ± 4.1; p = 0.06). No significant differences were observed in PROMIS-MMT, PAM, or Neuro-QoL measures. CONCLUSION: Findings suggest the feasibility of collecting PROs through an interactive web-based platform. The team-based remote BP monitoring demonstrated a favorable impact on patients' well-being. Patients equipped with appropriate resources can engage in poststroke self-care to mitigate inequities in health outcomes.


Assuntos
Acidente Vascular Cerebral , Telemedicina , Humanos , Qualidade de Vida , Pressão Sanguínea , Acidente Vascular Cerebral/terapia , Comprimidos
20.
Stroke ; 54(12): 3030-3037, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37909207

RESUMO

BACKGROUND: Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events. METHODS: This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite Z score. Using proportional odds regression, we quantified the association of the composite immune marker Z score, ICAS, and risk of vascular events. RESULTS: Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker Z score. Over an average follow-up of 12 years, we found that each unit increase in immune marker Z scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker Z scores and ICAS in their relationship with any longitudinal outcome. CONCLUSIONS: Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.


Assuntos
Arteriosclerose Intracraniana , Noma , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Fator A de Crescimento do Endotélio Vascular , Estudos Prospectivos , Constrição Patológica/complicações , Noma/complicações , Fatores de Risco , Arteriosclerose Intracraniana/complicações , Acidente Vascular Cerebral/epidemiologia , Biomarcadores , Artérias
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