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1.
BMC Cardiovasc Disord ; 24(1): 295, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851694

RESUMO

OBJECTIVE: This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). METHOD: In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People's Hospital and Lianyungang First People's Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. RESULT: The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11-2.39, OR = 1.72,95%CI = 1.16-2.55, OR = 2.06,95%CI = 1.36-3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566-0.623;P<0.001). CONCLUSION: Summarily, the TyG index has slight significance in the identification of LAA and CE; it is particularly a marker for their preliminary identification.


Assuntos
Biomarcadores , Glicemia , AVC Isquêmico , Valor Preditivo dos Testes , Triglicerídeos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Triglicerídeos/sangue , Idoso , Pessoa de Meia-Idade , Biomarcadores/sangue , Glicemia/metabolismo , Glicemia/análise , Diagnóstico Diferencial , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Fatores de Risco , Curva ROC , Área Sob a Curva , Arteriosclerose Intracraniana/sangue , Arteriosclerose Intracraniana/diagnóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , China/epidemiologia
2.
Neurology ; 103(1): e209431, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38861688

RESUMO

BACKGROUND AND OBJECTIVES: Obesity is hypothesized to induce a hypercoagulable state that increases stroke risk. The molecular mechanisms underlying this association are largely uncharacterized. We aimed to apply mendelian randomization to identify whether the association of genetically proxied body mass index (BMI) with cardioembolic stroke risk is mediated by changes in levels of circulating coagulation factors. METHODS: Genetic proxies for BMI and levels of circulating coagulation factors were obtained, respectively, from the Genetic Investigation of ANthropometric Traits consortium (n = 694,649) and deCODE cohort (n = 35,559). Genetic associations with cardioembolic stroke risk were obtained from the GIGASTROKE consortium (10,804 cases and 1,234,804 controls). We performed a two-sample mendelian randomization analysis testing the association of genetically proxied BMI with cardioembolic stroke risk, genetically proxied BMI with levels of coagulation factors, and genetically proxied levels of coagulation factors with cardioembolic stroke risk. These estimates were carried forward to mediation and sensitivity analyses. RESULTS: A 1-SD increase in genetically proxied BMI associated with increased cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD of BMI 1.20, 95% CI 1.08-1.33, p = 8.65 × 10-4) with similar findings in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants. Genetically proxied BMI was further associated with increased levels of Factor VII, Factor Xa, Factor XI, and Protein S (all p < 5.9 × 10-6). Of these factors, genetically proxied levels of Factor XI were associated with cardioembolic stroke risk (OR of cardioembolic stroke per 1-SD increase in Factor XI levels 1.32, 1.19-1.46, p = 6.18 × 10-8). The mediated effect of genetically proxied BMI through Factor XI accounted for 26% (6%-49%) of the total effect of BMI on cardioembolic stroke. DISCUSSION: Human genetic data support increased levels of Factor XI as a mechanistic explanation for how obesity increases cardioembolic stroke risk. The clinical relevance of this association warrants further investigation within ongoing clinical trials of Factor XI inhibition.


Assuntos
Índice de Massa Corporal , Análise da Randomização Mendeliana , Obesidade , Trombofilia , Humanos , Obesidade/genética , Obesidade/complicações , Obesidade/sangue , Obesidade/epidemiologia , Trombofilia/genética , Trombofilia/sangue , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/sangue , Feminino , Fatores de Coagulação Sanguínea/genética , Masculino , Fatores de Risco , AVC Embólico/genética , AVC Embólico/epidemiologia
3.
J Am Heart Assoc ; 13(12): e033201, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38844434

RESUMO

BACKGROUND: Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. METHODS AND RESULTS: We performed a nested case-control study within the Dongfeng-Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow-up period of 6.1±2.3 years. Fifty-five metabolites in fasting plasma were measured by ultra-high-performance liquid chromatography-mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08-1.34] and 1.22 [1.09-1.36], respectively; both Benjamini-Hochberg-adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios [95% CIs]: 1.16 [1.03-1.31] and 1.39 [1.07-1.81], respectively), while glutamate was associated with only IS (odds ratios [95% CI]: 1.26 [1.11-1.43]). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). CONCLUSIONS: This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.


Assuntos
Arginina , Biomarcadores , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Metabolômica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Estudos de Casos e Controles , Incidência , Biomarcadores/sangue , AVC Isquêmico/epidemiologia , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/sangue , Acidente Vascular Cerebral Hemorrágico/diagnóstico , Metabolômica/métodos , Arginina/sangue , Arginina/análogos & derivados , Medição de Risco , Idoso , Ácido Glutâmico/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Adulto , População do Leste Asiático
4.
Sci Rep ; 14(1): 13976, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886511

RESUMO

Stroke is an acute cerebrovascular disease in which blood flow to the brain is suddenly disrupted, causing damage to nerve cells. It involves complex and diverse pathophysiological processes and the treatment strategies are also diverse. The treatment for patients with stroke and atrial fibrillation (AF) is aimed at suppressing thrombus formation and migration. However, information regarding the protein networking involved in different thrombus formation pathways in patients with AF and stroke is insufficient. We performed protein profiling of patients with ischemic stroke with and without AF to investigate the mechanisms of thrombus formation and its pathophysiological association while providing helpful information for treating and managing patients with AF. These two groups were compared to identify the protein networks related to thrombus formation in AF. We observed that patients with ischemic stroke and AF had activated inflammatory responses induced by C-reactive protein, lipopolysaccharide-binding protein, and alpha-1-acid glycoprotein 1. In contrast, thyroid hormones were increased due to a decrease in transthyretin and retinol-binding protein 4 levels. The mechanism underlying enhanced cardiac activity, vasodilation, and the resulting thrombosis pathway were confirmed in AF. These findings will play an essential role in improving the prevention and treatment of AF-related stroke.


Assuntos
Fibrilação Atrial , Trombose , Humanos , Fibrilação Atrial/metabolismo , Trombose/metabolismo , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Proteínas Sanguíneas/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/sangue , AVC Isquêmico/metabolismo , Mapas de Interação de Proteínas , Proteômica/métodos
5.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891934

RESUMO

Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.


Assuntos
Metaloproteinase 9 da Matriz , Acidente Vascular Cerebral , Inibidor Tecidual de Metaloproteinase-1 , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Humanos , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Masculino , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/sangue , Feminino , Estudos Prospectivos , Idoso , Recuperação de Função Fisiológica , Pessoa de Meia-Idade , Reabilitação do Acidente Vascular Cerebral , Biomarcadores/sangue
6.
Brain Behav ; 14(6): e3577, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873864

RESUMO

OBJECTIVE: The research intended to probe the connection between the risk of stroke and serum vitamin D levels. METHODS: Three electronic databases (Cochrane Library, EMBASE, PubMed) were searched according to the subject terms from inception until July 29, 2022, and retrieved researches were screened on the basis of inclusion and exclusion criteria. Two investigators conducted the quality assessment and data extraction. Using Stata 16.0 software, a meta-analysis was conducted on the extracted data. FINDINGS: In total, 27 studies with 45,302 participants were included. Among these studies, 20 focused on stroke risk, while 7 examined stroke prognosis. According to the meta-analysis findings, it was observed that a higher stroke risk is connected to reduced levels of serum vitamin D. This association was reflected in a combined relative risk (RR) of 1 .28 (95% confidence interval (CI): 1.15-1.42) and a worse prognosis after stroke (RR = 2.95, 95% CI: 1.90-4.60). Additional analysis indicated that no apparent relationship between a decrease in vitamin D and the probability of experiencing a hemorrhagic stroke was found. The RR found was 1.93 (95% CI: 0.95-3.95). On the other hand, it was observed that a reduction in serum vitamin D levels was linked to an elevated likelihood of developing an ischemic stroke. The RR identified was 1.72 (95% CI: 1.78-2.03). Moreover, a lower level of vitamin D in the bloodstream was associated with a more unfavorable prognosis for individuals who suffered from a stroke. The RR for this correlation was 2.95 (95% CI: 1.90-4.60). However, further research is required to confirm the above-mentioned findings. CONCLUSION: In conclusion, lower concentration vitamin D was found to be related to an increased risk of stroke, which could mainly be reflected in ischemic stroke patients but not in patients with hemorrhagic stroke. A lower serum vitamin D level was correlative with the poor prognosis of stroke.


Assuntos
Acidente Vascular Cerebral , Deficiência de Vitamina D , Vitamina D , Humanos , Prognóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Fatores de Risco , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , AVC Isquêmico/mortalidade
7.
Cardiovasc Diabetol ; 23(1): 215, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907337

RESUMO

BACKGROUND: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. METHODS: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. RESULTS: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. CONCLUSIONS: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status.


Assuntos
Biomarcadores , Glicemia , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Glicemia/metabolismo , Biomarcadores/sangue , China/epidemiologia , Medição de Risco , Incidência , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Estudos Longitudinais , Prognóstico , Resistência à Insulina , Triglicerídeos/sangue , HDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/diagnóstico , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Estudos Prospectivos
8.
Clin Appl Thromb Hemost ; 30: 10760296241254104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38772566

RESUMO

This study aims to identify risk factors for secondary venous thromboembolism (VTE) in stroke patients and establish a nomogram, an accurate predictor of probability of VTE occurrence during hospitalization in stroke patients. Medical Information Mart for Intensive Care IV (MIMIC-IV) database of critical care medicine was utilized to retrieve information of stroke patients admitted to the hospital between 2008 and 2019. Patients were randomly allocated into train set and test set at 7:3. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for secondary VTE in stroke patients. A predictive nomogram model was constructed, and the predictive ability of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). This study included 266 stroke patients, with 26 patients suffering secondary VTE after stroke. A nomogram for predicting risk of secondary VTE in stroke patients was built according to pulmonary infection, partial thromboplastin time (PTT), log-formed D-dimer, and mean corpuscular hemoglobin (MCH). Area under the curve (AUC) of the predictive model nomogram was 0.880 and 0.878 in the train and test sets, respectively. The calibration curve was near the diagonal, and DCA curve presented positive net benefit. This indicates the model's good predictive performance and clinical utility. The nomogram effectively predicts the risk probability of secondary VTE in stroke patients, aiding clinicians in early identification and personalized treatment of stroke patients at risk of developing secondary VTE.


Assuntos
Nomogramas , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Feminino , Masculino , Acidente Vascular Cerebral/sangue , Idoso , Fatores de Risco , Pessoa de Meia-Idade , Bases de Dados Factuais
9.
Cardiovasc Diabetol ; 23(1): 170, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750553

RESUMO

OBJECTIVE: Although the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization. METHODS: We recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups. RESULTS: A total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121-1.400 and HR = 1.604, 95% CI 1.437-1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05). CONCLUSIONS: In patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency.


Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Bases de Dados Factuais , Valor Preditivo dos Testes , Triglicerídeos , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Glicemia/metabolismo , Triglicerídeos/sangue , Biomarcadores/sangue , Medição de Risco , Fatores de Risco , Fatores de Tempo , Prognóstico , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Parada Cardíaca/sangue , Parada Cardíaca/mortalidade , Parada Cardíaca/diagnóstico , Parada Cardíaca/terapia , Parada Cardíaca/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Hospitalização , Mortalidade Hospitalar
10.
Neuroscience ; 549: 138-144, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38734302

RESUMO

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.


Assuntos
Endarterectomia das Carótidas , Proteínas de Membrana , Complicações Pós-Operatórias , Acidente Vascular Cerebral , Endarterectomia das Carótidas/efeitos adversos , Humanos , Masculino , Idoso , Feminino , Proteínas de Membrana/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/sangue , Complicações Pós-Operatórias/metabolismo , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estenose das Carótidas/cirurgia , Interleucina-6/sangue , Interleucina-6/metabolismo , Proteínas do Tecido Nervoso
11.
Transl Psychiatry ; 14(1): 204, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762535

RESUMO

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins' plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.


Assuntos
Encéfalo , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Análise da Randomização Mendeliana , Proteoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Disfunção Cognitiva/sangue , Disfunção Cognitiva/genética , Disfunção Cognitiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Cognição , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/sangue , Testes de Estado Mental e Demência
12.
Sci Rep ; 14(1): 11222, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755170

RESUMO

Homocysteine (Hcy) and Hcy-thiolactone (HTL) affect fibrin clot properties and are linked to cardiovascular disease. Factors that influence fibrin clot properties and stroke are not fully understood. To study sulfur-containing amino acid metabolites, fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to stroke, we analyzed plasma and urine from 191 stroke patients (45.0% women, age 68 ± 12 years) and 291 healthy individuals (59.7% women, age 50 ± 17 years). Plasma and urinary levels of sulfur-containing amino acid metabolites and fibrin clot properties were significantly different in stroke patients compared to healthy individuals. Fibrin CLT correlated with fibrin Absmax in healthy males (R2 = 0.439, P = 0.000), females (R2 = 0.245, P = 0.000), female stroke patients (R2 = 0.187, P = 0.000), but not in male stroke patients (R2 = 0.008, P = ns). Fibrin CLT correlated with age in healthy females but not males while fibrin Absmax correlated with age in both sexes; these correlations were absent in stroke patients. In multiple regression analysis in stroke patients, plasma (p)CysGly, pMet, and MTHFR A1298C polymorphism were associated with fibrin Absmax, while urinary (u)HTL, uCysGly, and pCysGly were significantly associated with fibrin CLT. In healthy individuals, uHTL and uGSH were significantly associated with fibrin Absmax, while pGSH, and CBS T833C 844ins68 polymorphism were associated with fibrin CLT. In logistic regression, uHTL, uHcy, pCysGly, pGSH, MTHFR C677T polymorphism, and Absmax were independently associated with stroke. Our findings suggest that HTL and other sulfur-containing amino acid metabolites influence fibrin clot properties and the risk of stroke.


Assuntos
Fibrina , Homocisteína , AVC Isquêmico , Humanos , Masculino , Feminino , Homocisteína/sangue , Homocisteína/análogos & derivados , Homocisteína/metabolismo , Homocisteína/urina , Idoso , Pessoa de Meia-Idade , Fibrina/metabolismo , AVC Isquêmico/sangue , AVC Isquêmico/metabolismo , AVC Isquêmico/urina , Adulto , Tempo de Lise do Coágulo de Fibrina , Fatores de Risco , Aminoácidos Sulfúricos/sangue , Aminoácidos Sulfúricos/metabolismo , Aminoácidos Sulfúricos/urina , Aminoácidos/urina , Aminoácidos/sangue , Aminoácidos/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/urina
13.
Brain Behav ; 14(5): e3509, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38779748

RESUMO

OBJECTIVE: The purpose of this study was to investigate the predictive value of mean platelet volume (MPV) and platelet count (PC) in branch atheromatous disease (BAD). METHODS: This retrospective study included 216 patients with BAD-stroke within 48 h of symptom onset. These patients were divided into good and poor prognosis groups according to their 3-month modified Rankin scale scores after discharge. Multiple logistic regression analysis was used to evaluate independent predictors of poor prognosis in BAD-stroke patients. Receiver-operating characteristic (ROC) analysis was used to estimate the predictive value of MPV and PC on BAD-stroke. RESULTS: Our research showed that a higher MPV (aOR, 2.926; 95% CI, 2.040-4.196; p < .001) and PC (aOR, 1.013; 95% CI, 1.005-1.020; p = .001) were independently associated with poor prognosis after adjustment for confounders. The ROC analysis of MPV for predicting poor prognosis showed that the sensitivity and specificity were 74% and 84.9%, respectively, and that the AUC was .843 (95% CI, .776-.909, p < .001). The optimal cut-off value was 12.35. The incidence of early neurological deterioration (END) was 24.5% (53 of 163), and 66% of patients in the poor prognosis group had END (33 of 50). Multiple logistic regression analyses showed that elevated MPV and PC were associated with the occurrence of END (p < .05). CONCLUSION: Our results suggested that an elevated MPV and PC may be important in predicting a worse outcome in BAD-stroke patients. Our study also demonstrated an independent association of MPV and PC with END, which is presumably the main reason for the poor prognosis.


Assuntos
Volume Plaquetário Médio , Humanos , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Contagem de Plaquetas , Acidente Vascular Cerebral/sangue , Placa Aterosclerótica/sangue
14.
Stroke ; 55(6): 1601-1608, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38690658

RESUMO

BACKGROUND: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort. METHODS: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean Z-score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance. RESULTS: We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 [95% CI, 1.05-2.08]; P=0.024) and ischemic stroke (hazard ratio, 1.51 [95% CI, 1.03-2.21]; P=0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (ß±SE, 0.19±0.02; P<0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03; P=0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed. CONCLUSIONS: Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment.


Assuntos
Biomarcadores , Inflamação , Interleucina-18 , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Biomarcadores/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Pessoa de Meia-Idade , Interleucina-18/sangue , Idoso , Inflamação/sangue , Estudos de Coortes , Incidência , Fatores de Risco , Imageamento por Ressonância Magnética , Disfunção Cognitiva/sangue , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico por imagem
15.
J Clin Neurosci ; 124: 115-121, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703471

RESUMO

PURPOSE: Evidence is scarce regarding the association between hyponatremia and alterations in cognitive function among hospitalized older patients. We aimed to investigate the associations between hyponatremia and the baseline cognitive status, as well as the improvement in cognitive function, in hospitalized post-stroke patients. METHODS: This retrospective cohort study included consecutive hospitalized post-stroke patients. Serum sodium concentrations were extracted from medical records based on blood tests performed within 24 h of admission, with hyponatremia defined as a serum sodium concentration < 135 mEq/L. The main outcomes included admission and discharge scores for cognitive levels, assessed through the cognitive domain of the Functional Independence Measure (FIM-cognition), as well as the score changes observed during the hospitalization period. Multivariate linear regression analyses were used to determine the association between hyponatremia and outcomes of interest, adjusted for potential confounders. RESULTS: Data from 955 patients (mean age 73.2 years; 53.6 % men) were included in the analysis. The median baseline blood sodium level was 139 [137, 141], and 84 patients (8.8 %) exhibited hyponatremia. After full adjustment for confounders, the baseline hyponatremia was significantly and negatively associated with FIM-cognition values at admission (ß = -0.009, p = 0.016), discharge (ß = -0.038, p = 0.043), and the gain during hospital stay (ß = -0.040, p = 0.011). CONCLUSION: Baseline hyponatremia has demonstrated a correlation with decline in cognitive level over the course of rehabilitation in individuals after stroke. Assessing hyponatremia at the outset proves to be a pivotal prognostic indicator.


Assuntos
Disfunção Cognitiva , Hospitalização , Hiponatremia , Acidente Vascular Cerebral , Humanos , Hiponatremia/etiologia , Hiponatremia/sangue , Masculino , Feminino , Idoso , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/sangue , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Pessoa de Meia-Idade , Sódio/sangue
16.
Med Sci Monit ; 30: e943063, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809818

RESUMO

BACKGROUND The correlation between serum creatinine levels and the long-term prognosis of patients undergoing percutaneous coronary intervention (PCI) has not yet been systematically investigated. This study aimed to evaluate the association between long-term prognosis and serum creatinine levels in patients after PCI. MATERIAL AND METHODS This was an observational cohort study of 2533 patients who received PCI and completed serum creatinine and other tests in China. The study's primary prognostic indicators were the frequency of clinical adverse events, all-cause death, cardiac death, acute myocardial infarction, and stroke. All-cause death referred to death from all causes during the follow-up period, whereas cardiac death was death due to cardiac injury resulting in severe cardiac dysfunction or failure. Clinical events included death, ischemia, and stroke. Yao et al completed the entire study and uploaded the data to the DATADRYAD website. We used only this data for secondary analysis. RESULTS The study involved 2533 participants, with a mean age of 59.9±11.1 years and a median follow-up of 29.8 months. The analysis, controlling for confounding factors, revealed a positive correlation between serum creatinine and all-cause death (OR: 2.178, 95% CI: 1.317-3.603, P<0.05), which was confirmed by the results of sensitivity analysis (P for trend <0.05). However, no direct linear correlation was found between serum creatinine and acute myocardial infarction, cardiac death, or stroke. CONCLUSIONS There was a linear correlation between serum creatinine and all-cause death in the long-term prognosis of patients after PCI, independent of acute myocardial infarction, cardiac death, and stroke.


Assuntos
Creatinina , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Creatinina/sangue , Prognóstico , Idoso , China/epidemiologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Causas de Morte , Fatores de Risco , Estudos de Coortes , Acidente Vascular Cerebral/sangue
17.
J Affect Disord ; 360: 242-248, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38821370

RESUMO

BACKGROUND: Previous studies had reported depression symptoms and TG/HDLC ratio may share pathophysiological pathway. The aim was to investigate the combined effects of depression symptoms and TG/HDL-C ratio on the risk of CMM. METHODS: This cohort study extracted data from 2011 to 2018 of CHARLS. The CMM event occurred from 2013 to 2018, defined as suffering from more than one of stroke, cardiac events, and diabetes mellitus. Cox proportional hazards regression models were used to assess the association between the baseline combined effects of depression symptoms and TG/HDL-C ratio with incidence of CMM, stroke, cardiac events, and diabetes mellitus. RESULTS: A total of 8349 participants (3966 men and 4383 women) were included in the study, with a mean age of 58.5 years. During a 7-year follow-up survey, 370 (4.43 %) participants developed CMM. Compared to individuals with no depression symptoms and low TG/HDLC ratio, the multivariable-adjusted HRs (95%CI) for the new-onset CMM for patients with the depression symptoms alone, high TG/HDLC ratio alone, and depression symptoms and high TG/HDLC ratio were 1.37 (95 % CI = 0.95-1.98), 1.62 (95 % CI = 1.22-2.14), 1.94 (95 % CI = 1.39-2.72), respectively (P < 0.001). LIMITATIONS: Firstly, potential confounding factors such as dietary intake and nutrition were not collected at the time of study design. Secondly, exposure to the outcome was self-reported, which may cause recall bias or misclassification. Finally, the population was aged ≥45 years, so the results cannot be generalized to all age groups. CONCLUSION: Our findings indicated that patients with depression and high TG/HDLC ratio had a higher risk of developing CMM.


Assuntos
HDL-Colesterol , Depressão , Multimorbidade , Triglicerídeos , Humanos , Masculino , Feminino , China/epidemiologia , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Triglicerídeos/sangue , Depressão/epidemiologia , Depressão/sangue , Estudos Longitudinais , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/sangue , Modelos de Riscos Proporcionais , Incidência
18.
J Clin Neurosci ; 125: 43-50, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38749330

RESUMO

BACKGROUND: The D-dimer-to-fibrinogen ratio (DFR) is a good indicator of thrombus activity in thrombotic diseases, but its clinical role in acute ischaemic stroke (AIS) patients with different etiologies has not been studied. We evaluated the diagnostic value of the DFR for different subtypes of AIS. METHODS: We conducted a single-center retrospective study of 269 patients with AIS who were referred to our stroke center within 4.5 h from Jan 2017 to Oct 2019. Coagulation data including DFRs were compared among the different stroke subtypes, and a separate retrospective validation sample was utilized to evaluate the prediction efficiency of the DFR for subtype diagnosis. RESULTS: A higher DFR was observed in patients with cardioembolism than in those with large artery atherosclerosis (LAA) (odds ratio (OR) per 0.1 increase of the DFR: 1.49 [1.01-2.18]) after we adjusted for vascular risk factors. The diagnostic value of the DFR for detecting cardioembolism (AUC = 0.722, 95 % CI = 0.623-0.820) exceeded that of isolated D-dimer or fibrinogen. The validation sample (n = 117) further supported the notion that a diagnosis of cardioembolism was more common in patients with a DFR > 0.11 (multivariable risk ratio = 3.11[1.33-7.31], P = 0.009). CONCLUSION: High DFRs were associated with cardioembolism in patients with AIS. The utilization of DFR can be beneficial for distinguishing a cardiac embolic source from atherosclerotic stroke.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio , Humanos , Feminino , Masculino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/análise , Fibrinogênio/metabolismo , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Aterosclerose/complicações , Aterosclerose/sangue , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/complicações , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Biomarcadores/sangue , AVC Embólico/etiologia , AVC Embólico/sangue , AVC Embólico/diagnóstico
19.
Clin Chim Acta ; 560: 119730, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38810671

RESUMO

BACKGROUND: The association between S-adenosylhomocysteine (SAH) and stroke has not been confirmed due to the specialized equipment and time requirements necessary for S-adenosylhomocysteine testing. We aimed to explore the association between SAH and stroke. METHODS: A nested, case-control study drawn from the China Stroke Primary Prevention Trial of rural adults with hypertension, including 557 first stroke cases and 557 matched controls was conducted. Serum SAH was measured by stable-isotope dilution liquid chromatography-tandem mass spectrometry using 4500MD. Multiple conditional logistic regression models were used to evaluate the association between SAH and first stroke. RESULTS: In females, SAH levels were significantly higher in the stroke population than in the control group (16.0 ng/mL vs. 14.6 ng/mL). When SAH was assessed as quartiles, the odds of stroke were 1.78 (95 % CI: 1.02-3.09) in Quartile 2, 1.31 (95 % CI: 0.73-2.33) in Quartile 3, and 1.93 (95 % CI: 1.03-3.62) in Quartile 4, compared to Quartile 1. When Quartiles 2-4 were combined, the adjusted odds ratio of first stroke was 1.64 (95 % CI: 1.03-2.62) compared with Quartile 1. In subgroup analysis, a significant SAH-stroke association was observed in the lower vitamin D3 group (OR = 3.35, 95 % CI:1.72-6.53; P interaction, 0.035). In males, higher levels of SAH were associated with an increased risk of stroke in those under age 60. Compared with the reference group, the adjusted odds ratio of total stroke was 2.40 (95 % CI: 1.02-5.91) in the combined group (Quartile 2-4). In contrast, no significant association between SAH and stroke was found in males aged 60 or older. CONCLUSIONS: This study reveals that SAH is associated with a higher risk of stroke independently of homocysteine, especially in females. SAH may be a second predictor of stroke in the metabolic pathway of methionine, after homocysteine.


Assuntos
Hipertensão , S-Adenosil-Homocisteína , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , S-Adenosil-Homocisteína/sangue , Estudos de Casos e Controles , Hipertensão/sangue , Hipertensão/complicações , China/epidemiologia , Idoso , Adulto , Povo Asiático , População do Leste Asiático
20.
Sleep Med ; 119: 518-525, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38805859

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is increasingly recognized as a common condition in the general population and causes significant OSA-associated morbidities including cardiovascular and cerebrovascular events such as cerebral small vessel disease (CSVD) and stroke. METHODS: In this study, using sensitive ELISA immunoassays, we measured subset of endothelial/vascular and inflammatory biomarkers as well as neurofilament light chain (NfL), a sensitive marker for neuroaxonal injury, using plasma from OSA patients post-stroke (Acute Cerebral Infarction (ACI), N = 26) to determine their usefulness as potential prognostic markers in disease progression. RESULTS: Our results showed significantly increased plasma TNFα and NfL concentrations and decreased concentrations of platelet derived growth factor (PDGF-AA) in post-stroke OSA patients with more severe white matter hyperintensities (WMHs). And after separating the patients based on sex, compared to females, male post-stroke OSA patients with severe WMHs have increased circulating levels of inflammatory chemokine CXCL10 and cytokine Interleukin-10 (IL-10) and significantly decreased levels of Angiopoietin-1 (Ang-1) an important protein responsible for endothelial/vascular integrity functions. Importantly, in a subset of newly diagnosed OSA patients (without prior history of stroke), significantly increased plasma CXCL10 levels and decreased plasma Ang-1 levels were also readily observed when compared to healthy controls, indicating possible altered endothelial integrity and ongoing vascular inflammation in these newly diagnosed OSA patients. CONCLUSIONS: In summary, our study has identified a novel set of plasma biomarkers including PDGF-AA, CXCL10 and Ang-1 for their potential prognostic value for disease outcomes pre- and post-stroke in OSA patients and use as surrogate markers to measure efficacy of treatment modalities.


Assuntos
Biomarcadores , Apneia Obstrutiva do Sono , Acidente Vascular Cerebral , Humanos , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Masculino , Biomarcadores/sangue , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Idoso , Fator de Crescimento Derivado de Plaquetas/análise , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas de Neurofilamentos/sangue , Fator de Necrose Tumoral alfa/sangue , Quimiocina CXCL10/sangue , Angiopoietina-1/sangue , Inflamação/sangue , Interleucina-10/sangue
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