RESUMO
Hemoglobin variability is known to increase cardiovascular mortality in chronic kidney disease, but the association of hemoglobin variability with the risk of cardiovascular disease (CVD) in the general population is yet unclear. This retrospective cohort study based on 'the South Korean National Health Insurance Service database' consisted of 198,347 adults who went through all three health examinations. Hemoglobin variability is defined as the average successive variability of three separate hemoglobin values from each health screening period. Participants were followed up for 6 years to determine the risk of coronary heart disease and stroke. We used multivariate Cox proportional hazards regression to examine the adjusted hazard ratios for CVD according to hemoglobin variability. Per 1 unit increase of hemoglobin variability, the risk for CVD (aHR 1.06, 95% CI 1.02-1.09) and stroke (aHR 1.08, 95% CI 1.03-1.13) increased significantly. The risk-increasing trend was preserved in the low-to-moderate risk group of CVDs (aHR 1.07, 95% CI 1.02-1.11). This result suggests that subjects with high hemoglobin variability who would otherwise be categorized as having low-to-moderate CVD risk may have higher risk of CVD than those with low hemoglobin variability.
Assuntos
Doenças Cardiovasculares , Hemoglobinas , Adulto , Humanos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Hemoglobinas/análise , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Medição de RiscoRESUMO
Background: The aim of the study was to find the potential roles of B-type natriuretic peptide (BNP) and imaging markers on distinguishing cardioembolic (CE) stroke from non-CE stroke, so as to provide useful information for making individualized endovascular treatment (EVT) plan for the patients with acute ischemic stroke (AIS). Methods: The patients with unilateral anterior circulation large vessel occlusion who underwent EVT between March 2016 and December 2021 were analyzed in this study, retrospectively. The risk factors, laboratory test indicators, imaging parameters, and other factors were compared between the CE group and non-CE group. Logistic regression was used to analyze the risk factors of CE stroke. ROC curves were used to assess the values of different parameters on distinguishing CE stroke from non-CE stroke. The relationships between BNP and imaging parameters were assessed using the Spearman correlation analysis. Results: 160 patients were enrolled in the study and divided into the CE group (n = 66) and non-CE group (n = 94). BNP (odds ratio (OR) = 1.004; 95% CI, 1.001-1.009; p = 0.038), MMR (OR = 0.736; 95% CI, 0.573-0.945; p = 0.016), NIHSS (OR = 1.150; 95% CI, 1.022-1.294; p = 0.020), and AF (OR = 556.968; 95% CI, 51.739-5995.765; p < 0.001) were the independent predictive factors of CE stroke. The area under the curve (AUC) of BNP and mismatch ratio (MMR) were 0.846 (95% CI (0.780-0.898), p < 0.001) and 0.636 (95% CI (0.633-0.779), p < 0.001), respectively. The cut-off value of BNP was 249.23 pg/mL with the sensitivity of 74.24% and the specificity of 82.98%. BNP combined with MMR improved the predictive value for CE stroke. The AUC of the combination was 0.858 with the sensitivity of 84.85% and the specificity of 73.40%. BNP was correlated with 4D CTA collateral score, MMR, clot burden score, final infarct volume, infarct core volume, and ischemic penumbra volume (all, p < 0.05). Conclusion: BNP on admission combined with MMR is valuable for the risk prediction of CE stroke, which will promote the further screening of the high-risk patients with CE stroke and provide more diagnostic information for clinicians.
Assuntos
AVC Embólico , Peptídeo Natriurético Encefálico , Biomarcadores/análise , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico por imagem , AVC Embólico/sangue , AVC Embólico/diagnóstico por imagem , Humanos , Infarto/complicações , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico por imagem , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
To investigate the prognostic potential of serum aldehyde dehydrogenase isoform 1 (ALDH1) level in acute cerebral infarction, and the molecular mechanism in mediating neurological deficits, a total of 120 acute cerebral infarction cases within 72 h of onset were retrospectively analyzed. Serum ALDH1 level in them was detected by qRT-PCR. Receiver operating characteristic (ROC) and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of ALDH1 in acute cerebral infarction, respectively. An in vivo acute cerebral infarction model in rats was established by performing MCAO, followed by evaluation of neurological deficits using mNSS and detection of relative levels of ALDH1, Smad2, Smad4, and p21 in rat brain tissues. Pearson's correlation test was carried out to verify the correlation between ALDH1 and mNSS and relative levels of Smad2, Smad4, and p21. Serum ALDH1 level increased in acute cerebral infarction patients. A high level of ALDH1 predicted a poor prognosis of acute cerebral infarction patients. In addition, ALDH1 was sensitive and specific in distinguishing acute cerebral infarction cases, presenting a certain diagnostic potential. mNSS was remarkably higher in acute cerebral infarction rats than that of controls. Compared with sham operation group, relative levels of ALDH1, Smad2, and Smad4 were higher in brain tissues of modeling rats, whilst p21 level was lower. ALDH1 level in brain tissues of modeling rats was positively correlated to mNSS, and mRNA levels of Smad2 and Smad4, but negatively correlated to p21 level. Serum ALDH1 level is a promising prognostic and diagnostic factor of acute cerebral infarction, which is correlated to 90-day mortality. Increased level of ALDH1 in the brain of cerebral infarction rats is closely linked to neurological function, which is associated with the small mothers against decapentaplegic (Smad) signaling and p21.
Assuntos
Família Aldeído Desidrogenase 1 , Infarto Cerebral , Retinal Desidrogenase , Família Aldeído Desidrogenase 1/sangue , Família Aldeído Desidrogenase 1/metabolismo , Animais , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/metabolismo , Infarto Cerebral/sangue , Infarto Cerebral/metabolismo , Humanos , Prognóstico , Isoformas de Proteínas/sangue , Isoformas de Proteínas/metabolismo , Ratos , Retinal Desidrogenase/análise , Retinal Desidrogenase/sangue , Retinal Desidrogenase/metabolismo , Estudos Retrospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/metabolismoRESUMO
BACKGROUND AND AIMS: Strokes are the second highest cause of death in the world and the most common cause of permanent disability in adults. Intestinal barrier permeability thus contributes to diminished homeostasis within the body, which further affects the healing process and convalescence. Each stroke patient should be administered with ingredients that support the intestinal barrier (e.g., protein and fiber). The aim of this study was to compare the effect of various types of diet (enteral with or without fiber vs. a mixed kitchen diet) on the metabolic activity of intestinal microbiota, namely short chain fatty acids, and gut barrier integrity parameters (zonulin and calprotectin. METHODS: Patients (n = 59), after suffering an ischemic stroke, were randomly allocated to three groups receiving: the kitchen diet (n = 32; 1.2 g fiber in 100 mL); Nutrison Energy® (n = 14; 0.02 g fiber in 100 mL); and Nutrison Diason Energy HP® (n = 13; 1.8 g fiber in 100 mL). The patients underwent anthropometric measurements and blood samples (for prealbumin measurements), and stool samples (for zonulin and calprotectin determinations) were taken twice, on admission and a week later. RESULTS: Industrial diets enriched with fiber maintained nutritional status and had a beneficial effect on intestinal barrier permeability parameters. Patients fed with kitchen diets demonstrated a decreased number of lymphocytes, hemoglobin, erythrocytes, and increased serum concentration of C-reactive protein, but improved gut barrier markers. Proton pump inhibitors were shown to increase the inflammatory process in gut. CONCLUSIONS: Stroke patients should be administered with industrial diets enriched with fiber to improve gut barrier integrity and nutritional parameters.
Assuntos
Fibras na Dieta , Microbioma Gastrointestinal , Mucosa Intestinal , Acidente Vascular Cerebral , Adulto , Permeabilidade da Membrana Celular , Fibras na Dieta/administração & dosagem , Nutrição Enteral , Humanos , Mucosa Intestinal/metabolismo , Complexo Antígeno L1 Leucocitário , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/dietoterapia , Acidente Vascular Cerebral/microbiologiaRESUMO
BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. RESULTS: We observed associations of intermediate monocytes, early-activated CD4+ T cells, and both CD4+ and CD8+ T cells producing interleukin-4 after cytokine stimulation (Th2 and Tc2, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.
Assuntos
Aterosclerose , Interleucina-4 , Acidente Vascular Cerebral , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Aterosclerose/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos , Citocinas/biossíntese , Citocinas/sangue , Citocinas/imunologia , Feminino , Seguimentos , Humanos , Incidência , Inflamação , Interleucina-4/biossíntese , Interleucina-4/sangue , Interleucina-4/imunologia , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , AVC Isquêmico/imunologia , Ativação Linfocitária/imunologia , Masculino , Monócitos/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Vitronectin (VTN) is a glycoprotein enriched in the blood and activates integrin receptors. VTN blood levels increase only in female mice 24 h after an ischemic stroke and exacerbate brain injury through IL-6-driven inflammation, but the VTN induction mechanism is unknown. Here, a 30 min middle cerebral artery occlusion (MCAO) in female mice induced VTN protein in the liver (normally the main source) in concert with plasma VTN. Male mice were excluded as VTN is not induced after stroke. MCAO also increased plasma VTN levels after de novo expression of VTN in the liver of VTN-/- female mice, using a hepatocyte-specific (SERPINA1) promoter. MCAO did not affect SERPINA1 or VTN mRNA in the liver, brain, or several peripheral organs, or platelet VTN, compared to sham mice. Thus, hepatocytes are the source of stroke-induced increases in plasma VTN, which is independent of transcription. The cholinergic innervation by the parasympathetic vagus nerve is a potential source of brain-liver signaling after stroke. Right-sided vagotomy at the cervical level led to increased plasma VTN levels, suggesting that VTN release is inhibited by vagal tone. Co-culture of hepatocytes with cholinergic neurons or treatment with acetylcholine, but not noradrenaline (sympathetic transmitter), suppressed VTN expression. Hepatocytes have muscarinic receptors and the M1/M3 agonist bethanechol decreased VTN mRNA and protein release in vitro via M1 receptors. Finally, systemic bethanechol treatment blocked stroke-induced plasma VTN. Thus, VTN translation and release are inhibited by muscarinic signaling from the vagus nerve and presents a novel target for lessening detrimental VTN expression.
Assuntos
Acidente Vascular Cerebral , Vitronectina , Animais , Betanecol , Colinérgicos , Feminino , Infarto da Artéria Cerebral Média , Integrinas , Fígado/metabolismo , Camundongos , RNA Mensageiro , Acidente Vascular Cerebral/sangue , Nervo Vago/fisiologia , Vitronectina/sangueRESUMO
OBJECTIVE: To investigate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and the incidence of acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). METHODS: A total of 257 patients admitted to the Kaifeng Central Hospital were enrolled in this study. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression analysis were used to determine the association between Lp-PLA2 and AIS in patients with AF. RESULTS: In AF group, plasma Lp-PLA2 concentrations were significantly higher in patients with AIS than in those without it (277.4 vs 155.1, p < 0.001). And in the group of AIS patients, patients with AF also had a significantly higher level of Lp-PLA2 concentration than those without (277.4 vs 204.2, p < 0.001). The analysis of the ROC curve showed a significant diagnostic value of Lp-PLA2 for the incidence of AIS in patients with AF (AUC = 0.840, 95% CI: 0.737-0.871, p < 0.001), and the optimal cut-off point was 220.5 ng/ml, with a sensitivity and specificity of 82.14% and 75.5%, respectively. All AF patients were divided into two subgroups: the high Lp-PLA2 group (≥220.5 ng/ml) and the low Lp-PLA2 group (<220.5 ng/ml). And multivariate logistic regression analysis showed that after adjustment of confounders, Lp-PLA2 (OR 12.48, 95%CI 5.73-27.16, p < 0.001) was independently associated with the incidence of AIS in patients with AF. CONCLUSIONS: Plasma Lp-PLA2 concentration was independently associated with the development of AIS in patients with AF. Lp-PLA2 is a potential biomarker for stratification of risk for AIS in patients with AF.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase , Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Fibrilação Atrial/sangue , Fibrilação Atrial/enzimologia , Biomarcadores/sangue , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/enzimologia , Curva ROC , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/enzimologiaRESUMO
Objective: To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up. Methods: A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models. Results: The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL. Conclusion: Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/análise , Doenças Cardiovasculares/diagnóstico , Valor Preditivo dos Testes , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/sangue , Fatores de Risco , Acidente Vascular Cerebral/sangueRESUMO
Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.
Assuntos
Caracteres Sexuais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Estrogênios/sangue , Feminino , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/sangueRESUMO
Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.
Assuntos
Isquemia Encefálica/imunologia , COVID-19/imunologia , Imunidade Celular/fisiologia , Trombose Intracraniana/imunologia , Neutrófilos/imunologia , Acidente Vascular Cerebral/imunologia , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/sangue , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , COVID-19/sangue , COVID-19/genética , Feminino , Humanos , Trombose Intracraniana/sangue , Trombose Intracraniana/genética , Masculino , Trombólise Mecânica/métodos , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estudos Prospectivos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genéticaRESUMO
Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s-1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke.
Assuntos
Eritrócitos/patologia , Policitemia Vera/sangue , Policitemia Vera/patologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Adulto , Estudos Transversais , Agregação Eritrocítica/fisiologia , Deformação Eritrocítica/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/patologia , Trombose/sangue , Trombose/patologiaRESUMO
AIM: Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. METHODS: We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). CONCLUSION: These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.
Assuntos
Adiponectina/sangue , Adiponectina/metabolismo , Infarto Cerebral/sangue , Infarto Cerebral/metabolismo , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Peso Molecular , Sobrepeso/sangue , Sobrepeso/metabolismo , Isoformas de Proteínas/sangue , Isoformas de Proteínas/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/metabolismoRESUMO
OBJECTIVES: There is accumulating evidence that periodontal disease is associated with atrial fibrillation (AF) or stroke, but it is unclear which causative species of periodontal disease are present in stroke patients with AF. We aimed to investigate the associations between AF and specific periodontal pathogens using serum titers of IgG antibodies of bacteria in acute stroke patients. MATERIALS AND METHODS: Acute stroke patients were registered at two hospitals. Serum samples were evaluated for titers of antibodies against 9 periodontal pathogens (16 genotypes) using ELISAs. We identified AF in patients according to the following criteria: (1) a history of sustained or paroxysmal AF or (2) AF detection upon arrival or during admission. We carried out propensity score matching to categorize the patients as those with AF and those without. RESULTS: Of the 664 acute stroke patients, 123 (18.5%) had AF. After propensity score matching, 234 patients were selected. Patients with AF had a higher prevalence of positive serum titers of antibodies against Porphyromonas gingivalis (FimA type III) and Porphyromonas gingivalis (FimA type V) than those without AF (59.0% vs. 39.3%, p=0.004 and 58.2% vs. 40.2%, p=0.009, respectively). CONCLUSIONS: Porphyromonas gingivalis, especially FimA type III and type V, might be associated with AF in stroke patients.
Assuntos
Fibrilação Atrial , Imunoglobulina G , Doenças Periodontais , Porphyromonas gingivalis , Acidente Vascular Cerebral , Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Humanos , Imunoglobulina G/sangue , Doenças Periodontais/epidemiologia , Doenças Periodontais/microbiologia , Porphyromonas gingivalis/imunologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for stroke. Stroke is also an independent risk factor for worse CKD outcomes and inflammation may contribute to this bidirectional relationship. This study aims to investigate inflammatory biomarkers in patients with non-dialysis CKD (ND-CKD) with and without stroke. METHODS: A propensity matched sample from > 3000 Salford Kidney Study (SKS) patients, differentiated by previous stroke at study recruitment, had stored plasma analyzed for interleukin- 6 (IL-6), Von Willebrand Factor (VWF) and C-reactive protein (CRP). Multivariable cox regression analysis investigated associations between inflammation and death, end-stage renal disease (ESRD) and future non-fatal cardiovascular events (NFCVE). RESULTS: A total of 157 previous stroke patients were compared against 162 non-stroke patients. There were no significant differences in inflammatory biomarkers between the two groups. Previous stroke was associated with greater mortality risk, hazard ratio (HR) (95% CI) was 1.45 (1.07-1.97). Higher inflammatory biomarker concentrations were independently associated with death but not ESRD or NFCVE in the total population. For each 1 standard deviation (SD) increase in log IL-6, VWF and CRP, the HR for all-cause mortality were 1.35 (1.10-1.70), 1.26 (1.05-1.51) and 1.34 (1.12-1.61), respectively. CRP retained its independent association (HR 1.47 (1.15-1.87)) with death in the stroke population. CONCLUSION: Previous stroke is an important determinant of mortality. However, the adverse combination of stroke and ND-CKD does not seem to be driven by higher levels of inflammation detected after the stroke event. Biomarkers of inflammation were associated with worse outcome in both stroke and non-stroke ND-CKD patients. TRIAL REGISTRATION: 15/NW/0818 .
Assuntos
Proteína C-Reativa/análise , Inflamação/sangue , Inflamação/etiologia , Interleucina-6/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Fator de von Willebrand/análise , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pontuação de PropensãoRESUMO
Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.
Assuntos
Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , HumanosRESUMO
Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.
Assuntos
Peptídeos beta-Amiloides/sangue , Demência/sangue , Fragmentos de Peptídeos/sangue , Proteínas tau/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Cognição , Demência/etiologia , Complicações do Diabetes/sangue , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Medição de Risco , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicaçõesAssuntos
Apolipoproteínas E/antagonistas & inibidores , Neurotoxinas/biossíntese , Fragmentos de Peptídeos/antagonistas & inibidores , Receptores Nicotínicos/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apolipoproteínas E/uso terapêutico , Humanos , Fragmentos de Peptídeos/uso terapêutico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
OBJECTIVES: This research aims to study the prognostic role of serum S100 as a predictor of mortality in vascular and traumatic brain injuries. METHODS: This prospective cohort study involved 219 patients. In the blood serum, neuron-specific markers (S100, NSE) and glucose, acid-base state and gas composition of arterial blood were obtained at admission, on the 3rd, 5th and 7th days of patients' stay in the intensive care unit. RESULTS: The most significant risk factor for an unfavorable outcome is the marker S100 with a cut-off point of 0.2 mcg/l. The analysis results indicate a statistically significant direct relationship between S100 > 0.2 mcg/l and NSE ≥ 18.9 ng/ml compared to other variables, while the chance ratio (OR) is 11.9 (95%CI:3.2927-1.6693;). With blood sugar increase above 7.4 mmol/l, the OR is 3.82 (95% CI: 2.1289-0.5539;); with a Glasgow scale below 13 points, the OR is 3.69 (95% CI: 2.1316-0.4819;); with an increase in pCO2 < 43.5 mm Hg, the OR was 3.15 (95% CI: 1.8916- 0.4062;). The obtained model certainty measure according to pseudo R2 Nagelkerke criterion is 263.5, showing the excellent quality of the mathematical model's predictive ability. The developed prognostic model, including the dependent variable S100 and independent variables as predictors of a poor outcome of NSE, pCO2, GCS and Hb, reached a cut-off point of 84.51%, AUC - 0.88 with high levels of sensitivity and specificity: 91.89% and 64.14%, respectively. NOVELTY: This model can be used to predict the outcome in patients with acute cerebral pathology.
Assuntos
Lesões Encefálicas Traumáticas/diagnóstico , Hipóxia/diagnóstico , Fosfopiruvato Hidratase/sangue , Proteínas S100/sangue , Acidente Vascular Cerebral/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Lesões Encefálicas Traumáticas/sangue , Feminino , Humanos , Hipóxia/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/sangue , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized. We evaluated the nature and impact of collaterals on outcomes in the late time window DAWN trial (Diffusion-Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo). METHODS: The DAWN Imaging Core Lab prospectively scored collateral grade on baseline computed tomography angiography (CTA; endovascular and control arms) and digital subtraction angiography (DSA; endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade (American Society of Interventional and Therapeutic Neuroradiology collateral score). Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes were separately analyzed for each treatment arm. RESULTS: Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0-3) and DSA (n=57; median 2, 1-4) before thrombectomy in 161 DAWN subjects (mean age 69.8±13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (Tan grade 3, n=64 [44%]; 2, n=45 [31%]; 1, n=31 [22%]; 0, n=4 [3%]). DSA also showed a diverse range of collateral grades (ASITN grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except atrial fibrillation (41.6% endovascular versus 25.0% controls, P=0.04), and CTA collateral grades were balanced. Differences were seen across the 3 levels of collateral flow (good, fair, poor) for baseline National Institutes of Health Stroke Scale, blood glucose <150, diabetes, previous ischemic stroke, baseline and 24-hour core infarct volume, baseline and 24-hour Alberta Stroke Program Early CT Score, dramatic infarct progression, final Thrombolysis in Cerebral Infarction 2b+, and death. Collateral flow was a significant predictor of 90-day modified Rankin Scale score of 0 to 2 in the endovascular arm, with 43.7% (31/71) of subjects with good collaterals, 30.8% (16/52) of subjects with fair collaterals, and 17.7% (6/34) of subjects with poor collaterals reaching modified Rankin Scale score of 0 to 2 at 90 days (P=0.026). CONCLUSIONS: DAWN subjects enrolled at 6 to 24 hours after onset with limited infarct cores had a wide range of collateral grades on both CTA and DSA. Even in this late time window, better collaterals lead to slower stroke progression and better functional outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02142283.
Assuntos
Angiografia Cerebral , Circulação Colateral , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Acidente Vascular Cerebral , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/cirurgiaRESUMO
Using standard techniques during mechanical thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (NCT03153683) isolates intracranial arterial blood distal to the thrombus and proximal systemic blood in the carotid artery. We augmented the current protocol to study leukocyte subpopulations both distal and proximal to the thrombus during human stroke (n = 16 patients), and from patients with cerebrovascular disease (CVD) undergoing angiography for unrelated conditions (e.g. carotid artery stenosis; n = 12 patients). We isolated leukocytes for flow cytometry from small volume (<1 mL) intracranial blood and systemic blood (5-10 mL) to identify adaptive and innate leukocyte populations, in addition to platelets and endothelial cells (ECs). Intracranial blood exhibited significant increases in T cell representation and decreases in myeloid/macrophage representation compared to within-patient carotid artery samples. CD4+ T cells and classical dendritic cells were significantly lower than CVD controls and correlated to within-patient edema volume and last known normal. This novel protocol successfully isolates leukocytes from small volume intracranial blood samples of stroke patients at time of mechanical thrombectomy and can be used to confirm preclinical results, as well as identify novel targets for immunotherapies.
