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1.
Stroke ; : STROKEAHA119026872, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597550

RESUMO

Background and Purpose- Stroke and Alzheimer disease are 2 major causes of neurological disability in aged people and shared overlapping predictors. In recent prospective studies, high Lp(a) [lipoprotein(a)] level is associated with high risk of stroke but low risk of Alzheimer disease. Whether this reflects a causal association remains to be established. The aim of this study is to examine the causal associations of Lp(a) concentrations on ischemic stroke, ischemic stroke subtypes, and Alzheimer disease. Methods- We used 9 single-nucleotide polymorphisms associated with Lp(a) concentrations as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the Multiancestry Genome-Wide Association Study of Stroke consortium with European individuals ≤446 696 individuals. Summary-level data on Alzheimer disease were obtained from the International Genomics of Alzheimer Project With European individuals ≤54 162 individuals. Two-sample Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches, and MR-Egger regression was used to explore pleiotropy. Results- Genetically predicted 1-SD log-transformed increase in Lp(a) concentrations was associated with a substantial increase in risk of large artery stroke (odds ratio, 1.20; 95% CI, 1.11-1.30; P<0.001) and a reduce in risk of small vessel stroke (odds ratio, 0.92; 95% CI, 0.88-0.97; P=0.001) and Alzheimer disease (odds ratio, 0.94; 95% CI, 0.91-0.97; P<0.001) using inverse-variance weighted method. No significant association was observed for total ischemic stroke or cardioembolic stroke. MR-Egger indicated no evidence of pleiotropic bias. Results were broadly consistent in sensitivity analyses using penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches accounting for potential genetic pleiotropy or outliers. Conclusions- This study provides evidence to support that high Lp(a) concentrations was causally associated with an increased risk of large artery stroke but a decreased risk of small vessel stroke and Alzheimer disease. The mechanism underlying the double-edged sword effect of Lp(a) concentrations on neurological system requires further investigation.

2.
JAMA Neurol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424481

RESUMO

Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA. Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. Design, Setting, and Participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. Main Outcomes and Measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. Conclusions and Relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

3.
Neurol Res ; 41(10): 893-899, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31328681

RESUMO

Objectives: Although statin therapy is associated with lower recurrence in patients with acute ischaemic stroke, data-evaluating associations between inpatient statin use and stroke recurrence in diabetic patients after acute stroke onset are limited. Methods: This study was based on population data from the Chinese National Stroke Registry. Patients with acute ischaemic stroke and no history of statin therapy were selected. Individuals treated regularly with any type or dosage of statins during acute hospitalization were defined as having inpatient statin therapy. The subjects were divided into two groups according to statin use status during acute hospitalization. Multivariate logistic regression analysis was used to analyse the associations between statin use and stroke recurrence in patients with or without diabetes. Results: A total of 11,429 patients, 2341 (20.48%) with diabetes, were selected for analysis. Statin therapy during hospitalization was documented in 4982 (43.59%). Logistic analysis showed no significant associations between inpatient statin use and stroke recurrence in diabetic subjects at 3 months (OR = 0.90, 95% CI = 0.69-1.16, P = 0.40) or 1 year (OR = 0.92, 95% CI = 0.74-1.16, P = 0.48), but statin use was significantly associated with lower recurrence in non-diabetic patients at both 3 months (OR = 0.80, 95% CI = 0.69-0.92, P = 0.002) and 1 year (OR = 0.82, 95% CI = 0.72-0.93, P = 0.002) after discharge. Conclusion: Inpatient statin use was associated with lower stroke recurrence in non-diabetic patients after acute ischaemic stroke, but no definite association between inpatient statin use and stroke recurrence in patients with diabetes mellitus was found.

4.
Platelets ; : 1-7, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357901

RESUMO

The study aimed to compare the efficacy and safety outcome associated with a short and a prolonged duration of thienopyridine therapy in patients with chronic kidney disease (CKD) after coronary stenting. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 January 2019 for studies comparing short and prolonged thienopyridine therapy in patients with CKD. Ischemic and bleeding events were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Seven studies comprising a total of 17,628 CKD patients were included in the evaluation. Prolonged duration of thienopyridine use, when compared to short-term thienopyridine, was associated with reduced risk of all-cause mortality (odds ratio 0.75, 95% confidence interval: 0.70-0.81, P< .001) and stent thrombosis (OR: 0.54, 95% CI 0.32 to 0.89; P< .001), but the odds of myocardial infarction (OR: 0.91, 95% CI: 0.77-1.07; P = .23) and stroke (OR: 0.91, 95% CI 0.73 to 1.13; P = .38) did not differ according to different duration of thienopyridine. As for bleeding events, long-term thienopyridine therapy did not significantly increase the bleeding (OR: 0.95, 95% CI 0.79 to 1.14; P = .58). In these patients with CKD following PCI, prolonged thienopyridine therapy compared with short-term therapy, was associated with reduced all-cause mortality and stent thrombosis, without any significant difference in myocardial infarction, stroke, and bleeding. Thienopyridine prolongation decisions for CKD patients should be individualized after careful consideration of the benefit-risk balance.

5.
BMJ ; 365: l2211, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171523

RESUMO

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Plaquetas/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
6.
Neurotox Res ; 36(4): 836-843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31127478

RESUMO

The "obesity paradox" was reported in patients with stroke. We aimed to evaluate the pattern and magnitude of association between body mass index (BMI) and prognosis of stroke in patients with minor ischemic stroke or transient ischemic attack (TIA). A total of 5163 patients with available BMI data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial were included. Patients were classified into three groups according to their BMI values: normal weight (< 23.9 kg/m2), overweight (24-27.9 kg/m2), and obese (≥ 28.0 kg/m2). The efficacy outcomes included a new stroke (ischemic or hemorrhagic), poor functional outcome defined as modified Rankin scale ≥ 2 points and death from any cause within 90 days. The interaction effects were determined using multivariable Cox or logistic regression models. After 90 days of follow up, there were 513 new strokes. Overweight (BMI 24-27.9 kg/m2) patients had a higher risk of recurrent strokes than those with normal weight (10.8% vs 8.8%; HR = 1.24, 95% CI 1.02-1.50) after adjusting for the baseline covariates, but no significant association was observed for those who were obese (P = 0.37). No significant association was found between being overweight or obese and poor functional outcome or death. For patients with a minor ischemic stroke or TIA, being overweight was associated with an increased risk of recurrent stroke compared to being of normal weight in our study.Trial registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00979589.

7.
Scand Cardiovasc J ; 53(2): 55-61, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30909763

RESUMO

BACKGROUND: The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD). METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23-1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p < 0.00001), myocardial infarction (RR1.74, 95% CI 1.29 to 2.33; p = 0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p = 0.004). CONCLUSIONS: Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.

9.
Neurol Res ; 41(5): 473-479, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822264

RESUMO

BACKGROUND: Recombinant tissue plasminogen activator (rt-PA) has been used as the standard treatment for acute ischemic stroke (AIS). The following study investigates whether low-dose rt-PA can decrease the incidence of symptomatic intracranial haemorrhage (sICH) in AIS patients with high-risk sICH compared to standard-dose rt-PA. MATERIALS AND METHODS: Data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) studies were assessed to explore risk factors for sICH after intravenous thrombolysis. For high-risk sICH patients (age ≧70 years old, or with diabetes, or serum glucose on admission >9.0 mmol/L, or NIHSS on admission>20, or with cardioembolism), standard-dose rt-PA (0.85 to 0.95 mg/kg) and low- dose rt-PA (0.5 to 0.7 mg/kg) were compared. Primary outcome measure was the incidence of sICH, and the secondary outcome measures were 7-day mortality and 90-day functional independence outcome (modified Rankin scale, 0-2). RESULTS: A total of 554 patients were enrolled (60 cases for low dose, and 494 cases for standard dose). Median rt-PA doses were 0.63 and 0.90 mg, respectively. After adjustment for the baseline variables, low-dose rt-PA did not decrease the incidence of sICH (per SITS-MOST criteria, 3.33% versus 2.23%, P = 0.3467) compared to low dose. The low-dose group revealed less functional independence outcomes (modified Rankin scale, 0-2) compared to standard-dose group (36.67% versus 52.43%; odds ratio = 0.49; p = 0.0204) at 90 days. CONCLUSIONS: Our study suggests that low-dose intravenous rt-PA for high-risk sICH stroke in Chinese patients may not decrease the incidence of sICH, and concomitant with a poor outcome compared to standard-dose rt-PA. ABBREVIATIONS: rt-PA: recombinant tissue plasminogen activator; AIS: acute ischemic stroke; sICH: symptomatic intracranial haemorrhage.


Assuntos
Fibrinolíticos/administração & dosagem , Hemorragias Intracranianas/prevenção & controle , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Glicemia , Complicações do Diabetes/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Incidência , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Fatores de Risco , Resultado do Tratamento
10.
J Clin Endocrinol Metab ; 104(7): 3039-3048, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30896740

RESUMO

OBJECTIVE: The relationship between age at natural menopause and type 2 diabetes mellitus (T2DM) has yielded conflicting results, particularly when confounded by the presence of obesity. We therefore aimed to examine the association between age at natural menopause and development of T2DM and the influence of postmenopausal obesity status on this association. DESIGN: The data for this study was derived from one center (Beijing) of the REACTION study. After screening through our inclusion and exclusion criteria, 2689 postmenopausal women who completed a 3-year follow-up were included. Logistic regression analysis was conducted to clarify the association of the age at natural menopause with the development of T2DM. RESULTS: After adjustment for potential confounders, there was no significant association between the age at natural menopause and development of T2DM for all subjects. However, when subjects were stratified along the postmenopausal obesity status at baseline, in the presence or absence of obesity, we found a surprising contradictory association in two subgroups: late menopause (age >50 years) was associated with an increased risk (OR, 1.45; 95% CI, 1.02 to 2.05) of developing T2DM in the postmenopausal group without obesity, whereas we found a reduced risk (OR, 0.43; 95% CI, 0.27 to 0.71) in the postmenopausal group with obesity. Moreover, we found that early menopausal women (age ≤45 years) with postmenopausal obesity had the highest risk (OR, 2.10; 95% CI, 1.11 to 4.00) of developing T2DM compared with all other postmenopausal women. CONCLUSIONS: Postmenopausal obesity status may influence the association of age at natural menopause and the development of T2DM.

11.
JAMA Neurol ; 76(5): 552-560, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30742211

RESUMO

Importance: Genetic variants of ABCB1 may affect intestinal absorption of clopidogrel bisulfate. However, it is unclear whether ABCB1 polymorphisms are associated with clopidogrel efficacy for minor ischemic stroke or transient ischemic attack (TIA). Objectives: To investigate the association between ABCB1 polymorphisms and clopidogrel efficacy for minor stroke or TIA. Design, Setting, and Participants: In this prespecified secondary analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, 3010 patients with minor stroke or TIA at 73 sites in China with experience in conducting genetic studies were included from October 1, 2009, to July 30, 2012. The analysis was conducted on March 20, 2018. Four single-nucleotide polymorphisms (ABCB1 -154T>C [rs4148727], ABCB1 3435C>T [rs1045642], CYP2C19*2 [681G>A, rs4244285], and CYP2C19*3 [636G>A, rs4986893]) were genotyped among 2836 patients treated with clopidogrel plus aspirin (n = 1414) or aspirin alone (n = 1422). The association of ABCB1 genetic variants (-154 TC/CC and 3435 CT/TT) with clopidogrel efficacy was evaluated in the context of CYP2C19 status, another gene associated with clopidogrel efficacy. Interventions: Patients in the CHANCE trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. Main Outcomes and Measures: Primary efficacy outcome was stroke recurrence after 3 months. The safety outcome was any bleeding risk after 3 months. Results: Among 2836 patients, the median age was 61.8 years (interquartile range, 54.4-71.1 years) and 1887 patients (66.5%) were male. A total of 2146 (75.7%) patients were carriers of ABCB1 -154 TC/CC (570 [20.1%]) or 3435 CT/TT (1851 [65.3%]) genotype. Clopidogrel plus aspirin treatment was associated with reduced risk of new stroke in patients with ABCB1 -154 TT and 3435 CC genotype (hazard ratio [HR], 0.43; 95% CI, 0.26-0.71) but not in those with ABCB1 -154 TC/CC or 3435 CT/TT genotype (HR, 0.78; 95% CI, 0.60-1.03) compared with aspirin (P = .04 for interaction). A combined association of ABCB1 and CYP2C19 polymorphisms with new stroke was observed. The risk of bleeding for clopidogrel plus aspirin treatment was not associated with the ABCB1 genotypes (2.3% and 1.3% vs 1.9% and 2.2%; P = .25 for interaction in patients with or without ABCB1 -154 TC/CC or 3435 CT/TT genotype). Conclusions and Relevance: The ABCB1 polymorphism was associated with the reduced efficacy of clopidogrel plus aspirin treatment compared with aspirin among patients with minor ischemic stroke or TIA. Genetic polymorphism of ABCB1 should be considered when prescribing clopidogrel for these patients. Trial Registration: ClinicalTrials.gov identifier: NCT00979589.

12.
BMC Neurol ; 19(1): 7, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621613

RESUMO

BACKGROUND: Single acute infarction (SAI) usually had lower risk of stroke recurrence than multiple acute infarctions (MAIs) in minor stroke. To evaluate whether all SAI had lower risk of stroke recurrence than MAIs in minor stroke. METHODS: We derived data from the imaging subgroup of the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Minor stroke were categorized into SAI and MAIs by infarction numbers in diffusion weighted imaging. SAI were classified as lacunar infarction and non-lacunar infarction. The outcome was stroke recurrence within one-year follow-up. We assessed the associations between infarction patterns and stroke recurrence using multivariable Cox regression models. RESULTS: Overall, 834 patients with minor stroke were included in this subgroup, 553 SAI (381 lacunar infarction, 172 non-lacunar infarction) and 281 MAIs. The rate of stroke recurrence was 7.6%, 15.1% and 15.3% in lacunar infarction of SAI, non-lacunar infarction of SAI and MAIs at one year, respectively. Compared with MAIs, lacunar infarction of SAI had lower risk of stroke recurrence (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.21-0.80, P = 0.009), but not in non-lacunar infarction of SAI (HR 1.01, 95% CI 0.60-1.69, P = 0.98). CONCLUSIONS: Lacunar infarction of SAI have lower risk of stroke recurrence than MAIs, while non-lacunar infarction of SAI might have similar risk as MAIs. Except for the number of infarctions, size and location should also be considered to stratify risk of stroke recurrence in minor stroke. TRIAL REGISTRATION: http://www.clinicaltrials.gov Unique identifier: NCT00979589 . Date of registration: September 2009.


Assuntos
Infarto Encefálico/patologia , Clopidogrel/administração & dosagem , Acidente Vascular Cerebral Lacunar/patologia , Acidente Vascular Cerebral/patologia , Idoso , Imagem de Difusão por Ressonância Magnética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Fatores de Risco , Resultado do Tratamento
13.
J Stroke Cerebrovasc Dis ; 28(3): 800-806, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30553646

RESUMO

BACKGROUND: We aimed to externally validate the Get With the Guidelines (GWTG) risk model for all stroke types to predict in-hospital stroke mortality in Chinese patients and moreover to explore its prognostic value in predicting 3-month mortality after stroke. METHODS: The prognostic model was applied to patients with acute stroke from China National Stroke Registry II (CNSR II) to predict in-hospital and 3-month mortality. Model discrimination was estimated by calculating c-statistic and 95% confidence intervals (CIs). Calibration was assessed by Pearson correlation coefficient and Hosmer-Lemeshow test. RESULTS: Date from 21,684 stroke patients with complete data for in-hospital mortality prediction and 20,348 stroke patients with complete data for 3-month mortality prediction in the CNSR II were abstracted. The in-hospital and 3-month mortality were 1.4% and 5.6%, respectively. The c-statistics in the CNSR II were .86 (95% CI, .84-.88) and .83 (95% CI, .81-.84) for in-hospital and 3-month mortality, respectively. Calibration plot presented high correlation between the observed and predicted mortality rates (Pearson correlation coefficient, .996 for in-hospital and .998 for 3-month mortality; both P < .001). The Hosmer-Lemeshow statistics for the prediction of in-hospital and 3-month mortality were 0.21 and less than .001, respectively. The model performed nearly as well in each stroke type as in the overall model including all types. CONCLUSIONS: The GWTG risk model for all stroke types is a valid clinical tool to predict in-hospital and 3-month mortality in Chinese patients with acute stroke of any type.


Assuntos
Mortalidade Hospitalar , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo
14.
Artigo em Inglês | MEDLINE | ID: mdl-30497898

RESUMO

BACKGROUND: The association of prediabetes and outcome of patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between prediabetes and outcome of ischemic stroke or TIA. METHODS: We comprehensively searched the PubMed and Excerpt Medica Database(EMBASE) from their inceptions to August 25, 2017. Studies that reported outcomes of patients with ischemic stroke or TIA and with information on prediabetic states at baseline were included. The end points were new stroke, mortality, and poor outcome (modified Rankin Scale score of 3-6 or 2-6). RESULTS: A total of 8 studies with 10,975 patients with ischemic stroke or TIA were included in this meta-analysis, among which 4 studies reported the endpoint of new stroke, 5 studies reported mortality, and 6 studies reported poor outcome. Prediabetes was at increased risk of stroke compared with normal glucose metabolism (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.13-1.80; P = .003). Poor outcome was also more frequent in patients with prediabetes compared with normal glucose metabolism (odds ratio: 1.33, 95%CI: 1.11-1.59; P = .002), while mortality was not significant (HR: 1.69, 95%CI: 0.84-3.40; P = .14). There was no evidence of statistical heterogeneity among the included studies for stroke and poor outcome, but for mortality. CONCLUSIONS: Prediabetes was associated with an increased risk of new stroke and poor outcome, compared with normal glucose metabolism among patients with ischemic stroke or TIA.

15.
Biomed Pharmacother ; 110: 203-212, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30476721

RESUMO

The role of OPA1-related mitochondrial fusion in brain reperfusion stress has remained elusive. The aim of our study is to explore whether melatonin alleviates cerebral IR injury by modulating OPA1-related mitochondrial fusion. We found that melatonin reduced infarct area and suppressed neuron death during reperfusion stress. Biological studies have revealed that IR-inhibited mitochondrial fusion was largely reversed by melatonin via upregulated OPA1 expression. Knocking down OPA1 abrogated the protective effects of melatonin on mitochondrial energy metabolism and mitochondrial apoptosis. In addition, we also found that melatonin modified OPA1 expression via the Yap-Hippo pathway; blockade of the Yap-Hippo pathway induced neuron death and mitochondrial damage despite treatment with melatonin. Altogether, our data demonstrated that cerebral IR injury is closely associated with defective OPA1-related mitochondrial fusion. Melatonin supplementation enhances OPA1-related mitochondrial fusion by activating the Yap-Hippo pathway, ultimately reducing brain reperfusion stress.

16.
Brain Behav ; : e01154, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30456898

RESUMO

BACKGROUND: It has been shown that intracranial artery stenosis (ICAS) plays a key role in Chinese ischemic stroke or transient ischemic attack (TIA) patients. Many vascular diseases can lead to ICAS, such as atherosclerosis, dissection, vasculitis, moyamoya disease, and reversible cerebral vasoconstriction syndrome (RCVS). In addition, progression of intracranial atherosclerotic disease (ICAD) will increase the risk of ischemic cerebrovascular events. The ICASMAP study primarily aims to determine the etiology and disease distribution of ICAS using noninvasive magnetic resonance (MR) imaging and evaluate the rate for progression of ICAD in symptomatic population. METHODS: The ICASMAP study is a prospective, observational, and multicenter study by recruiting 300 subjects (18-80 years old) with recent stroke or TIA (within 2 weeks after onset of symptoms) in China. All the subjects will undergo MR imaging examination including brain and intracranial artery MR imaging at baseline. In addition, the clinical risk factors will be collected and blood biomarkers will be tested. A subgroup of more than 200 subjects who were diagnosed with ICAD according to baseline MR imaging will be followed up for 2 years. During the follow-up study, MR imaging examination will be performed at 12 and 24 months. The primary end point is presence of progression of intracranial artery atherosclerotic plaques. CONCLUSIONS: The ICASMAP study investigates the etiology of ICAS and progression of ICAD in Chinese stroke patients and may help to improve the precise diagnosis and intervention of ICAS and stroke prevention.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30418583

RESUMO

Context: Elevated blood triglyceride levels are known to increase the risk of diabetes and prediabetes. However, it is still unclear whether elevated triglyceride levels are associated with inadequate glycemic control in type 2 diabetic patients. Objective: To investigate the association between elevated triglyceride levels and inadequate glycemic control among insulin-treated patients with type 2 diabetes. Design, Setting, and Patients: We recruited 20,108 type 2 diabetic patients who were treated with a sufficient dose of insulin. These patients were from the 2013 China National HbA1c Surveillance System study, which was a multi-center study conducted in Mainland China. Multivariate logistic regressions were used to assess the association of the triglyceride level with the inadequate glycemic control. Results: Overall, 56.0% of the included study subjects had elevated triglyceride levels (≥1.70mmol/L), and prevalence of HbA1c ≥7.0% (53 mmol/mol) and ≥6.5% (48 mmol/mol) was 67.2% and 83.4%, respectively. The adjusted odds ratios of HbA1c ≥7.0% were 1.06 (0.98-1.15), 1.35 (1.23-1.48) and 3.12 (2.76-3.53), respectively, for those with triglyceride levels in ranges of 1.70-2.29, 2.30-3.39 and ≥3.40 mmol/L compared to those with triglyceride levels of <1.70 mmol/L. There was a similar association between triglyceride levels and HbA1c ≥6.5%. This positive association was confirmed by subgroup analyses among different subpopulations. There was also a strong nonlinear dose-response relationship between the triglyceride level and inadequate glycemic control. Conclusions: Elevated triglyceride levels were strongly associated with inadequate glycemic control, thus suppressing triglyceride levels might benefit in attaining a more optimal glycemic control in type 2 diabetic patients.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30420835

RESUMO

Background: Basal and premixed insulin have been widely used for insulin therapy of type 2 diabetes mellitus (T2DM) in China. The aim of this study is to compare the sustained efficacy of basal and premixed insulin therapies in T2DM outpatients with insulin monotherapy. Materials and Methods: The survey was conducted in 602 hospitals across China from April to June in 2013. The participants included outpatients who were receiving basal or premixed insulin monotherapy for more than 3 months, and the outcome was attaining a glycated hemoglobin A1C (HbA1c) of <7.0% as a measure of sustained glycemic control. Results: A total of 49,119 T2DM outpatients on basal (n = 11,967) or premixed insulin (n = 37,152) monotherapy were included in the final analyses. Using multivariable model analysis, patients using premixed insulin exhibited a better glycemic control, with more outpatients achieving the target HbA1c level than those using basal insulin (model 1, OR 0.695, 95%CI 0.664-0.728; model 2, OR 0.708, 95%CI 0.676-0.742; model 3, OR 0.717, 95%CI 0.684-0.752; model 4, OR 0.750, 95%CI 0.715-0.787). Using subgroup analysis stratified by age, sex, duration of diabetes, duration of insulin treatment, and complications, still more outpatients in every subgroup treated with premixed insulin achieved the target HbA1c (HbA1c < 7%) than those receiving basal insulin. Conclusions: Premixed insulin monotherapy had a better glycemic control (HbA1c < 7.0%) than basal insulin monotherapy for Chinese T2DM outpatients in daily.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30366863

RESUMO

BACKGROUND: The intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) therapy is safe and efficient during the treatment of acute ischemic stroke. Nonetheless, the different outcomes among various stroke subgroups have limited data with regard to the safety and efficacy of cryptogenic stroke (CS). The present study compared the safety and efficacy when IVT with rt-PA was used for the treatment of CS and the other stroke subtypes. METHODS: This study classified the IVT with rt-PA patients within 4.5 hours after stroke onset, based on the trial of ORG 10172 in acute stroke treatment criteria in terms of diagnostic evaluation. The data were obtained from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database, a large multicenter prospective registry. A multivariable logistic regression model was employed to compare the differences between the subtypes in symptomatic intracerebral hemorrhage (sICH) within 7 days and studied the mortality and the outcome during 90 days. RESULTS: In total, 1118 patients were recruited; of these, 131 (11.7%) suffered from CS and 987 (88.3%) with the other etiology. In the CS group, patients were younger than those in the other etiology groups (P < .001). Moreover, it had a lower prevalence of previous stroke (P = .0117), receiving antiplatelet drug in 24 hours prior to thrombolysis (P = .0017), and functional independence (mRS > 1 before stroke, P = .003). The CS group had lower blood pressure (systolic blood pressure P = .0001; diastolic blood pressure; P = .0212) before thrombolysis, atrial fibrillation (P < .001), and diabetes mellitus (P = .0005). Transient ischemic attack, hypertension, hyperlipidemia, blood glucose, receiving anticoagulants in 24 hours prior to thrombolysis, and standard dosage of rt-PA were equally distributed in both groups. After the adjustment of confounders between the CS and the other subgroups, no obvious differences were observed in sICH rate and mortality (P > .05) The CS patients exhibited excellent recovery (mRS, 0-1; 63.78%) and functional independence (mRS, 0-2; 74.8%) than the large artery atherosclerosis patients. CONCLUSIONS: IVT with rt-PA is a safe and effective method for the treatment of CS patients.

20.
Front Neurol ; 9: 827, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30333790

RESUMO

Background and Purpose: A large body of literature reported the association of particulate matter (PM) with stroke in high-income countries. Few studies have examined the association between PM and stroke in middle- and low-income countries and considered the types of stroke. In this study, we examined the short-term effects of particulate matter <2.5 µm in diameter (PM2.5) and particulate matter <10 µm in diameter (PM10) on ischemic stroke mortality and hemorrhagic stroke mortality in Beijing, China. Methods: We used an ecological study design and quasi-Poisson generalized additive models to evaluate the association of PM2.5 and PM10 and cerebrovascular diseases mortality, as well as ischemic- and hemorrhagic stroke mortality. In the model, we controlled long-term and season trends, temperature, and relative humidity, the day of the week and air pollution. For cerebrovascular diseases mortality, we examined the effects stratified by sex and age with different lag days. Results: A total of 48,122 deaths for cerebrovascular disease (32,799 deaths for ischemic stroke and 13,051 deaths for hemorrhagic stroke) were included in the study. PM2.5 was associated with stroke mortality. The 10 µg/m3 increase of PM2.5 was associated with the increase of mortality, 0.27% (95% CI, 0.12-0.43%) for cerebrovascular diseases, 0.23% (95% CI, 0.04-0.42%) for ischemic stroke and 0.37% (95% CI, 0.07-0.67%) for hemorrhagic stroke -. The associations between PM10 and mortality were also detected for cerebrovascular diseases and ischemic stroke, but not in hemorrhagic stroke. The stratified analysis suggested age and gender did not modify the effects of PM on mortality significantly. Conclusions: Our study suggested that short-term exposure to ambient PM was associated with the risk of stroke mortality.

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