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1.
Expert Opin Investig Drugs ; 30(10): 1025-1035, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34555978

RESUMO

INTRODUCTION: Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients. AREAS COVERED: The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an alternative thrombolytic drug to alteplase, nerinetide as a promising neuroprotective agent, and glibenclamide for reducing edema in malignant hemispheric infarction. We discuss the use of ticagrelor and the promising novel category of factor XI inhibitors in the subacute phase after stroke. We offer our insights on combined rivaroxaban and antiplatelet therapy, PCSK-9 inhibitors, and other non-statin hypolipidemic agents, as well as novel antidiabetic agents that have been shown to reduce cardiovascular events in the long-term. EXPERT OPINION: Current approaches in stroke treatment and stroke prevention have already transformed stroke care from a linear one-for-all treatment paradigm to a more individualized approach that targets specific patient subgroups with novel pharmaceutical agents. This tendency enriches the therapeutic armamentarium with novel agents developed for specific stroke subgroups. ABBREVIATIONS: IVT: intravenous thrombolysis; RCTs: randomized-controlled clinical trials; TNK: Tenecteplase; COVID-19: Coronavirus 2019 Disease; EXTEND-IA TNK: The Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke trial; AIS: acute ischemic stroke; NNT: number needed to treat; MT: mechanical thrombectomy; sICH: symptomatic intracranial hemorrhage; mRS: modified Rankin Scale; AHA/ASA: American Heart Association/American Stroke Association; ESO: European Stroke Organization; NA-1: Nerinetide; ENACT: Evaluating Neuroprotection in Aneurysm Coiling Therapy; CTA: CT angiography; TIA: transient ischemic attack; CHANCE: Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; LOF: loss-of-function; PRINCE: Platelet Reactivity in Acute Nondisabling Cerebrovascular Events; THALES: Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA [acetylsalicylic acid] for Prevention of Stroke and Death; CHANCE-2: Clopidogrel With Aspirin in High-risk Patients With Acute Non-disabling Cerebrovascular Events II; FXI: Factor XI; PACIFIC-STROKE: Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-NonCardioembolic Stroke study; COMPASS: Cardiovascular Outcomes for People Using Anticoagulation Strategies; CANTOS-ICAD: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease; SAMMPRIS: Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis; WASID: Warfarin-Aspirin Symptomatic Intracranial Disease; SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels; LDL-C: low-density lipoprotein cholesterol; TST: Treat Stroke to Target; IMPROVE-IT: Improved Reduction of Outcomes: Vytorin Efficacy International Trial; PCSK9: proprotein convertase subtilisin-kexin type 9; FOURIER: Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; CLEAR: Cholesterol Lowering via Bempedoic acid, an ACL-inhibiting Regimen; REDUCE-IT: Reduction of Cardiovascular Events With EPA Intervention Trial; STRENGTH: Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia; ACCORD: Action to Control Cardiovascular Risk in Diabetes; ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; VADT: Veterans Affairs Diabetes Trial; GLP-1R: Glucagon-like peptide-1 receptor; SGLT2: sodium-glucose cotransporter 2; CONVINCE: COlchicine for preventioN of Vascular Inflammation in Non-CardioEmbolic stroke; PROBE: Prospective Randomized Open-label Blinded Endpoint assessment.


Assuntos
Anticolesterolemiantes/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Fibrinolíticos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Fator XI/antagonistas & inibidores , Fator XI/metabolismo , Humanos , Pró-Proteína Convertase 9/antagonistas & inibidores , Pró-Proteína Convertase 9/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
2.
Neurology ; 97(17): e1717-e1726, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34588272

RESUMO

BACKGROUND AND OBJECTIVES: We evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes. METHODS: Patients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models. RESULTS: Of the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%-7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3-6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8-7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3-8.5]). DICUSSION: In patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%-7.0% and differed according to the ischemic stroke subtype.


Assuntos
Diabetes Mellitus , Hemoglobina A Glicada/metabolismo , Controle Glicêmico , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia
3.
Front Immunol ; 12: 720363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447386

RESUMO

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Assuntos
Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Inflamação/sangue , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Influenza Humana/complicações , Acidente Vascular Cerebral/sangue , Viroses
4.
Int J Mol Sci ; 22(16)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34445740

RESUMO

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.


Assuntos
Aterosclerose/complicações , Biomarcadores/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Trombose/complicações , Animais , Humanos
5.
Medicine (Baltimore) ; 100(28): e26617, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260548

RESUMO

BACKGROUND: Stroke is the third leading cause of global year of life lost in all-age and second-ranked cause of disability adjusted life years in middle-aged and elder population. Therefore, it is critical to study the relationship between vascular-related risk factors and cerebrovascular diseases. Several cross-sectional studies have shown that Cystatin C (Cys C) is an independent risk factor for cerebrovascular diseases and levels of Cys C are significantly higher in stroke patients than in healthy individuals. In this meta-analysis, we introduce a Cox proportional hazards model to evaluate the causality between Cys C and the risk of cerebrovascular accident in the elderly. METHODS: We searched PubMed, EMBASE, the Web of Science, and the Cochrane Library from 1985 to 2019 for studies on the relationship between serum Cys C and incidence stroke with Cox proportional hazards models. We conducted a subgroup analysis of the selected studies to determine a connection between atherosclerosis and stroke. Finally, 7 research studies, including 26,768 patients without a history of cerebrovascular, were studied. RESULTS: After comparing the maximum and minimum Cys C levels, the hazard ratio for all types of stroke, including ischemic and hemorrhagic stroke, was 1.18 (95% confidence interval 1.04-1.31) with moderate heterogeneity (I2 = 43.0%; P = .119) in a fixed-effect model after pooled adjustment for other potential risk factors. In the subgroup analysis, the hazard ratio and 95% confidence interval for Cys C stratified by atherosclerosis was 1.85 (0.97-2.72). As shown in Egger linear regression test, there was no distinct publication bias (P = .153). CONCLUSION: Increased serum Cys C is significantly associated with future stroke events in the elderly, especially in patients with carotid atherosclerosis. Thus, serum levels of Cys C could serve as a predicted biomarker for stroke attack.


Assuntos
Aterosclerose/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Cistatina C/sangue , Acidente Vascular Cerebral/epidemiologia , Idoso , Aterosclerose/sangue , Doenças das Artérias Carótidas/sangue , Causalidade , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/epidemiologia , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/sangue
6.
Neurology ; 97(7): e695-e705, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34321360

RESUMO

OBJECTIVE: Because metabolic syndrome is a significant risk factor for cardio-cerebrovascular diseases and the relationship between metabolic syndrome (including its components) and the prognosis of stroke is controversial, this study was conducted to evaluate whether metabolic syndrome is associated with a high recurrence and mortality of stroke. METHODS: This study was registered in the PROSPERO database (CRD42020177118). We searched for relevant observational cohort studies published from inception to April 23, 2020, using PubMed, Embase, and the Cochrane Library. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. The primary and secondary outcomes were stroke recurrence and all-cause mortality, respectively. Leave-one-out sensitivity analyses and nonparametric trim-and-fill method were used to identify the stability of the results. RESULTS: Thirteen cohort studies comprising 59,919 participants >60 years of age were included for analysis. Overall, metabolic syndrome was significantly associated with stroke recurrence (relative risk [RR] 1.46, 95% CI 1.07-1.97, p = 0.02). Among the metabolic syndrome components, low levels of high-density lipoprotein cholesterol (HDL-C) (RR 1.32, 95% CI 1.11-1.57, p = 0.002) and ≥2 metabolic syndrome components (RR 1.68, 95% CI 1.44-1.94, p < 0.001) significantly predicted stroke recurrence, whereas elevated triglycerides, elevated waist circumference, hyperglycemia, and hypertension failed to account for risk factors for stroke recurrence. Moreover, metabolic syndrome, not its components, was significantly associated with all-cause mortality (RR 1.27, 95% CI 1.18-1.36, p < 0.001). The stability of these results was further confirmed by the leave-one-out sensitivity analyses and nonparametric trim-and-fill method. CONCLUSIONS: The present study indicates that metabolic syndrome and some of its components (low HDL-C and number of metabolic syndrome components) seem to be risk factors for stroke recurrence. Although metabolic syndrome is also associated with all-cause mortality, the role of its components in predicting all-cause mortality deserves further study.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco
7.
Nutr Metab Cardiovasc Dis ; 31(9): 2700-2706, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34218986

RESUMO

BACKGROUND AND AIMS: Gender-specific differences were found in serum uric acid (SUA) levels and the risk of isolated distal deep vein thrombosis (IDDVT). This study aimed to explore the association among gender, SUA, and IDDVT in stroke patients. METHODS AND RESULTS: Finally, 3404 patients were recruited and divided into two groups: IDDVT (n = 1233) and Non-IDDVT (n = 2171) groups. Propensity score matching (PSM) was conducted to match the patients. Binary logistic regression was adopted to explore the association between SUA and IDDVT, with the SUA divided into quartiles. After PSM, 975 patients were included in each group. Non-IDDVT group had a larger proportion of male than IDDVT group (64.9% vs. 52.7%, p < 0.001). Moreover, males showed higher SUA levels than females (316.7 ± 102.1 vs. 261.8 ± 94.0 µmol/L, t = 12.1, p < 0.001). The highest quartile of SUA (≥346 µmol/L) showed a lower risk of IDDVT (OR = 0.629, p = 0.001), while the lowest quartile (≤225 µmol/L) showed a higher risk of IDDVT (OR = 1.361, p = 0.022). CONCLUSION: In patients with stroke, SUA played a protective role in IDDVT. Females had a higher risk of IDDVT, which may be owing to the lower SUA levels than males. In clinical practice, more attention should be paid to the risk of IDDVT in females, especially those with lower SUA levels.


Assuntos
Disparidades nos Níveis de Saúde , Acidente Vascular Cerebral/sangue , Ácido Úrico/sangue , Trombose Venosa/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/epidemiologia
8.
Cells ; 10(6)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207058

RESUMO

Increased sensitivity of methods assessing the levels of neurofilament light chain (NfL), a neuron-specific intermediate filament protein, in human plasma or serum, has in recent years led to a number of studies addressing the utility of monitoring NfL in the blood of stroke patients. In this review, we discuss that elevated blood NfL levels after stroke may reflect several different neurobiological processes. In the acute and post-acute phase after stroke, high blood levels of NfL are associated with poor clinical outcome, and later on, the blood levels of NfL positively correlate with secondary neurodegeneration as assessed by MRI. Interestingly, increased blood levels of NfL in individuals who survived stroke for more than 10 months were shown to predict functional improvement in the late phase after stroke. Whereas in the acute phase after stroke the injured axons are assumed to be the main source of blood NfL, synaptic turnover and secondary neurodegeneration could be major contributors to blood NfL levels in the late phase after stroke. Elevated blood NfL levels after stroke should therefore be interpreted with caution. More studies addressing the clinical utility of blood NfL assessment in stroke patients are needed before the inclusion of NfL in the clinical workout as a useful biomarker in both the acute and the chronic phase after stroke.


Assuntos
Biomarcadores/sangue , Proteínas de Neurofilamentos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia , Animais , Axônios/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/patologia , Prognóstico
9.
J Stroke Cerebrovasc Dis ; 30(10): 105993, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34325270

RESUMO

OBJECTIVE: Higher adiponectin concentration has been associated with the presence of sarcopenia in individuals with cardiovascular diseases. Post-stroke individuals presented higher adiponectin concentrations than non-stroke ones. However, no previous study has investigated the association between the adiponectin concentration and skeletal muscle mass in post-stroke individuals. On the other hand, higher adiponectin concentration has been associated with a more favorable lipid profile and the physical activity level might regulate adiponectin concentration. These associations have not been studied in this population. Thus, the main objective of this study was to determine whether the adiponectin concentration is associated with: (1) body composition; (2) lipid profile; and (3) physical activity level in chronic post-stroke individuals. MATERIALS AND METHODS: This study was a correlational, cross-sectional exploratory study. Data on body composition and lipid profile were collected using a bioelectrical impedance analyzer (InBody® 720) and an automated method analyzer (CELL-DYN Ruby), respectively. The physical activity level was measured by the StepWatch® Activity Monitor and the serum adiponectin concentration was analyzed using an enzyme-linked immunosorbent assay kit. Correlation analyses were made using Spearman's rank correlation coefficient (rs). RESULTS: Twenty-one post-stroke participants took part in the study. The adiponectin concentration was associated with the following: skeletal muscle mass (rs = -0.78), skeletal muscle mass index (rs = -0.75) and high-density lipoprotein (rs = 0.43). CONCLUSIONS: A greater adiponectin concentration is associated with a lower skeletal muscle mass and a higher high-density lipoprotein level in chronic post-stroke individuals, but not with physical activity levels.


Assuntos
Adiponectina/sangue , Composição Corporal , Exercício Físico , Lipídeos/sangue , Músculo Esquelético/fisiopatologia , Acidente Vascular Cerebral/sangue , Idoso , Biomarcadores/sangue , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Regulação para Cima
10.
J Stroke Cerebrovasc Dis ; 30(8): 105896, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34144337

RESUMO

OBJECTIVES: French national guidelines recommend searching for anti-SS-A antibodies during the second-line assessment of stroke in adults < 55 years of age in the absence of an identified etiology. We aimed to assess the impact of finding anti-SS-A antibodies during the etiological investigations of stroke in young adults. METHODS: Medical files from all patients ≤ 55 years of age admitted to a single stroke unit during a five-year period and for whom anti-SS-A antibodies were positive were retrospectively analyzed. RESULTS: Twelve patients were included (9 women; median age 48.5 years), with a rate of anti-SS-A antibody positivity of 1.6% (95% confidence interval [0.71-2.55] %; 12/735 admissions). The etiologies of the 12 ischemic events based on the TOAST classification were large-artery atherosclerosis (n = 1), cardioembolism (n = 1), small-vessel disease (n = 1), other determined etiology (n = 3), multiple etiology (n = 1), and no determined etiology (n = 5). A connective tissue disease (CTD) was discovered in 8/12 patients (1 primary Sjögren's Syndrome, 1 mixed CTD, 1 systemic sclerosis, 2 antiphospholipid syndromes, 1 undetermined CTD, 2 lupus). Anti-SSA antibodies were not directly responsible for the stroke in any of the 12 cases. A link between the autoimmune disease and the neurological vascular episode could be hypothesized for four patients, but it never influenced the therapeutic decision. CONCLUSIONS: Finding anti-SS-A antibodies during the etiological assessment of a stroke of young adults is rare. However, it may be worthwhile to refer the patient to a rheumatologist/an internist because CTD may be discovered and may require specific follow-up.


Assuntos
Anticorpos Antinucleares/sangue , Autoimunidade , Acidente Vascular Cerebral/sangue , Adulto , Fatores Etários , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
11.
J Am Coll Cardiol ; 77(24): 3046-3057, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34140109

RESUMO

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology's (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC's Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
12.
Sci Rep ; 11(1): 11523, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075142

RESUMO

This pilot, randomized, open-label controlled study compared the basal-bolus regimens of insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in stroke patients with hyperglycemia receiving intensive care. The study recruited acute stroke patients requiring intensive care within 72 h (h) of onset and had blood glucose > 200 mg/dL. 50 patients received IG (n = 26) or NPH (n = 24) with added short-acting prandial regular insulin over a 72-h period. The primary end point was the percentage of glucose within 80-180 mg/dL assessed through continuous glucose monitoring. The baseline characteristics were comparable, except the IG had higher glucose pre-randomization than the NPH (290.69 ± 82.31 vs. 246.04 ± 41.76 mg/dL, P = 0.021). The percentage of time with glucose between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH (P = 0.341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH (P = 0.374). The percentage of time with glucose < 60 mg/dL was 0.14 ± 0.49% in the IG and 0.47 ± 1.74% in the NPH. Poststroke outcomes were not significantly different. In conclusion, IG is safe and equally effective as an NPH-based basal-bolus regimen for acute stroke patients with hyperglycemia receiving intensive care.Trial registration ClinicalTrials.gov, NCT02607943. Registered 18/11/2015, https://clinicaltrials.gov/ct2/show/NCT02607943 .


Assuntos
Cuidados Críticos , Hipoglicemia , Insulina Glargina/administração & dosagem , Acidente Vascular Cerebral , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/complicações , Hipoglicemia/tratamento farmacológico , Insulina Glargina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
13.
Biomed Res Int ; 2021: 5549796, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977104

RESUMO

Objective: The role of trimethylamine N-oxide (TMAO) in cardiovascular diseases has been highlighted. Nevertheless, the associations of large-artery atherosclerotic (LAA) stroke with TMAO and blood lipid-related indices are little investigated. Methods: A cross-sectional comparative study was performed on 50 patients with LAA stroke and 50 healthy controls. Basic demographic data, common vascular risk factors, and blood lipid-related indices were collected. Plasma TMAO was detected through liquid chromatography tandem mass spectrometry. Multivariable unconditional logistic regression analyses were run to assess the associations of LAA stroke with plasma TMAO level and blood lipid-related indices. The area under the curve (AUC) of the receiver operating characteristic (ROC) was computed to assess the diagnostic performance of plasma TMAO level and blood lipid-related indices for LAA stroke. Results: Compared with healthy controls, the elevated plasma TMAO level (odds ratio [OR], 7.03; 95% confidence interval [CI], 2.86, 17.25; p < 0.01) and Apo-B (OR, 1.74; 95% CI, 1.06, 2.85; p = 0.03) were observed in LAA stroke patients, while lower Apo-A1 (OR, 0.56; 95% CI, 0.34, 0.91; p = 0.02), Apo-A1 to Apo-B ratio (OR, 0.29; 95% CI, 0.15, 0.56; p < 0.01), and HDL-C (OR, 0.56; 95% CI, 0.35, 0.91; p = 0.02) were found in LAA stroke patients after adjusted for age and gender. Moreover, plasma TMAO (AUC, 0.89; 95% CI, 0.83, 0.95), Apo-A1 (AUC, 0.81; 95% CI, 0.72, 0.89), Apo-B (AUC, 0.81; 95% CI, 0.73, 0.90), Apo-A1 to Apo-B ratio (AUC, 0.85; 95% CI, 0.78, 0.93), and HDL-C (AUC, 0.81; 95% CI, 0.72, 0.89) showed good diagnostic values for LAA stroke in adjusted models. Conclusions: The plasma TMAO level, Apo-A1, Apo-B, and HDL-C are important biomarkers for LAA stroke patients.


Assuntos
Aterosclerose/complicações , Lipídeos/sangue , Metilaminas/sangue , Acidente Vascular Cerebral , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
14.
J Clin Neurosci ; 88: 191-196, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992183

RESUMO

Stroke remains a major factor causing death and disabilities such as cognitive impairment. There is conflicting evidence on the role and dynamics of high sensitivity C-reactive protein (hsCRP), an acute phase pro-inflammatory protein, in post-stroke cognitive impairment. This study evaluated cognitive impairment and examined its relationship with serum hsCRP in the first three months following stroke. Cognition was assessed using Montreal Cognitive Assessment test, while serum hsCRP concentrations were assessed using enzyme link immunosorbent assay kit. Data were processed using SPSS Statistics version 20.0. Sixty subjects, comprising of 30 stroke patients and 30 healthy subjects, matched for age, sex and level of education were studied. Cognitive impairment was observed among the stroke patients, while the healthy subjects showed normal cognitive function; and the difference in the cognitive scores of the two groups was highly significant (P = 0.001). There was higher prevalence of cognitive impairment among the stroke survivors compared to the non-stroke subjects. Serum hsCRP was significantly higher among the stroke survivors compared to the healthy subjects (P = 0.001). The high hsCRP level correlates well with duration of stroke and working memory domain of cognition. The data revealed a high prevalence of cognitive impairment and concurrent high serum hsCRP levels among stroke survivors in the first three months following stroke, in contrast with normal subjects. The high hsCRP level correlates with duration of stroke and working memory domain of cognition. The data suggest a role for serum hsCRP and inflammation in the development of post-stroke cognitive impairment.


Assuntos
Proteína C-Reativa/metabolismo , Disfunção Cognitiva/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Adulto , África/epidemiologia , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sobreviventes
15.
Neurology ; 97(6): e619-e628, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34031205

RESUMO

OBJECTIVE: To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke. METHODS: Using a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals. RESULTS: During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%-27.7%) and 13.6% (95% CI 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%-49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%). CONCLUSIONS: Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that metaPRS is predictive of stroke risk.


Assuntos
Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Modelos Estatísticos , Herança Multifatorial , Reprodutibilidade dos Testes , Medição de Risco/métodos , Medição de Risco/normas , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/prevenção & controle
16.
Prev Chronic Dis ; 18: E45, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33988499

RESUMO

INTRODUCTION: Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS: We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION: A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.


Assuntos
HDL-Colesterol/sangue , Acidente Vascular Cerebral/sangue , Feminino , Humanos , Masculino , Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia
17.
Cardiovasc Diabetol ; 20(1): 113, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039351

RESUMO

BACKGROUND: Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and subsequent cardiovascular disease (CVD). However, the effect of longitudinal changes in TyG index on the risk of CVD remains uncertain. This study aimed to investigate the association between change in TyG index and the risk of CVD in the general population. METHODS: The current study included 62,443 Chinese population who were free of CVD. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and change in TyG index was defined as the difference between the TyG index in 2010 and that in 2006. Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to examine the association between change in TyG index and the risk of CVD. RESULTS: During a median follow-up of 7.01 years, 2530 (4.05%) incident CVD occurred, including 2018 (3.23%) incident stroke and 545 (0.87%) incident myocardial infarction (MI). The risk of developing CVD increased with the quartile of change in TyG index, after adjustment for multiple potential confounders, the hazard ratios for the Q4 group versus the Q1 group were 1.37 (95% confidence interval [CI], 1.21-1.54) for the overall CVD, 1.38 (95% CI, 1.19-1.60) for stroke, and 1.36 (95% CI, 1.05-1.76) for MI. Restricted cubic spline analysis also showed a cumulative increase in the risk of CVD with increases in the magnitude of change in TyG index. The addition of change in TyG index to a baseline risk model for CVD improved the C-statistics (P = 0.0097), integrated discrimination improvement value (P < 0.0001), and category-free net reclassification improvement value (P < 0.0001). Similar results were observed for stroke and MI. CONCLUSIONS: Substantial changes in TyG index independently predict the risk of CVD in the general population. Monitoring long-term changes in TyG may assist with in the early identification of individuals at high risk of CVD.


Assuntos
Glicemia/análise , Doenças Cardiovasculares/sangue , Triglicerídeos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Adulto Jovem
18.
Neurology ; 97(2): e203-e214, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986139

RESUMO

OBJECTIVE: To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers. METHODS: Consecutive patients with PFO-related stroke were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood pre- and post-PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. RESULTS: Patients with PFO-related stroke (n = 254) were recruited and followed up to 4 years (median 2.01; interquartile range 0.77-2.54). Metabolite profiling in the discovery cohort (n = 12) identified homocysteine as the most significantly decreased factor in intracardiac plasma after PFO closure (false discovery rate 0.001). This was confirmed in a validation cohort (n = 181), where intracardiac total homocysteine (tHcy) was immediately reduced in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (ß 0.115; 95% confidence interval [CI] 0.047-0.183; p = 0.001). tHcy reduction was more dramatic in left atrium than right (p < 0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n = 61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (ß -0.208; 95% CI -0.375∼-0.058; p = 0.007). Residual shunting was again independently associated with persistently elevated tHcy (ß 0.184; 95% CI 0.051-0.316; p = 0.007). CONCLUSIONS: PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.


Assuntos
Forame Oval Patente/sangue , Forame Oval Patente/complicações , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Adulto , Biomarcadores/sangue , Feminino , Homocisteína/sangue , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808453

RESUMO

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.


Assuntos
Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/metabolismo , Biomarcadores/sangue , Humanos , Inflamação , Estimativa de Kaplan-Meier , Extremidade Inferior/irrigação sanguínea , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações
20.
Clin Interv Aging ; 16: 505-511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790545

RESUMO

Objective: Pneumonia is a common complication in patients with stroke. There was a close relationship between serum iron and inflammatory response. This study aimed to explore the relationship between serum iron levels and stroke-associated pneumonia (SAP). Methods: Patients with acute stroke were recruited from the First Affiliated Hospital of Wenzhou Medical University and divided into SAP group and Non-SAP group. The demographic and clinical data of the patients were collected via the medical records, and the blood samples were collected within 24 hours after admission. The predictive value of serum iron to SAP was evaluated by receiver operating characteristic curve (ROC) and binary Logistic regression models. A restricted cubic spline (RCS) was used to furtherly clarify the relationship between serum iron and the risk of SAP. Results: A total of 906 participants were enrolled, including Non-SAP group (n = 755) and SAP group (n = 151). Serum iron levels in the SAP group were significantly lower than those in the Non-SAP group (9.77±5.61 vs 14.01±6.80, P < 0.001). Logistic regression showed that patients with high serum iron levels (≥7.8µmol/L) showed a lower risk of SAP (OR=0.43, 95% CI, 0.27-0.69, P < 0.001). Besides, the RCS model showed that there was an L-shaped relationship between the serum iron and risk of SAP (P for non-linearity: 0.014). Conclusion: Low serum iron level was a risk factor for SAP, and there was an L-shaped relationship between them. Stroke patients with low serum iron levels should be alert to the risk of SAP.


Assuntos
Ferritinas/sangue , Pneumonia/sangue , Acidente Vascular Cerebral/complicações , Idoso , Biomarcadores/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pneumonia/etiologia , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue
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