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1.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066757

RESUMO

Despite advances in diagnostic, prognostic, and treatment modalities, myocardial infarction (MI) remains a leading cause of morbidity and mortality. Impaired cellular signaling after an MI causes maladaptive changes resulting in cardiac remodeling. MicroRNAs (miRNAs/miR) along with other molecular components have been investigated for their involvement in cellular signaling in the pathogenesis of various cardiac conditions like MI. miRNAs are small non-coding RNAs that negatively regulate gene expression. They bind to complementary mRNAs and regulate the rate of protein synthesis by altering the stability of their targeted mRNAs. A single miRNA can modulate several cellular signaling pathways by targeting hundreds of mRNAs. This review focuses on the biogenesis and beneficial effects of cellular and circulating (exosomal) miRNAs on cardiac remodeling after an MI. Particularly, miR-1, -133, 135, and -29 that play an essential role in cardiac remodeling after an MI are described in detail. The limitations that will need to be addressed in the future for the further development of miRNA-based therapeutics for cardiovascular conditions will also be discussed.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular , Animais , Biomarcadores/sangue , MicroRNA Circulante/uso terapêutico , Humanos , Modelos Biológicos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Estabilidade de RNA/genética
2.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809145

RESUMO

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.


Assuntos
Arritmias Cardíacas/sangue , Infarto do Miocárdio/sangue , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Idoso , Animais , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/cirurgia , Feminino , Hemoglobina A Glicada/genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/genética , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Suínos , Resultado do Tratamento , Troponina/sangue
3.
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
4.
Medicine (Baltimore) ; 100(10): e24944, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725857

RESUMO

INTRODUCTION: The morbidity and mortality of acute myocardial infarction patients still remains high after percutaneous coronary intervention (PCI). Myocardial ischemia-reperfusion (MIR) injury is one of the important reasons. Although the phenomenon of MIR injury can paradoxically reduce the beneficial effects of myocardial reperfusion, there currently remains no effective therapeutic agent for preventing MIR. Previous studies have shown that Yiqi Liangxue Shengji prescription (YLS) is effective in improving clinical symptoms and ameliorating the major adverse cardiovascular events of coronary heart disease patients undergoing PCI. This study aims to evaluate the effectiveness and safety of YLS in patients with acute myocardial infarction (AMI) after PCI. METHODS: This study is a randomized, double-blinded, placebo-controlled, single-central clinical trial. A total of 140 participants are randomly allocated to 2 groups: the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with YLS and the placebo group will be treated with YLS placebo. All participants will receive a 8-week treatment and then be followed up for another 12 months. The primary outcome measures are N terminal pro B type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction. Secondary outcomes are plasma levels of microRNA-145, plasma cardiac enzyme, and Troponin I levels in blood samples, changes in ST-segment in ECG, Seattle Angina Questionnaire, the efficacy of angina symptoms, and occurrence of major adverse cardiac events. All the data will be recorded in case report forms and analyzed by SPSS V.17.0. DISCUSSION: The trial will investigate whether the postoperative administration of YLS in patients with AMI after PCI will improve cardiac function. And it explores microRNAs (miRNA)-145 as detection of blood-based biomarkers for AMI by evaluating the relation between miRNAs in plasma and cardiac function. TRIAL REGISTRATION: Chinese Clinical Trials Registry identifier ChiCTR2000038816. Registered on October 10, 2020.


Assuntos
Doença das Coronárias/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/cirurgia , Medicamentos de Ervas Chinesas/farmacologia , Eletrocardiografia , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Troponina I/sangue , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
6.
Clin Interv Aging ; 16: 465-474, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33758500

RESUMO

Background: Amino acids play essential roles in protein construction and metabolism. Our study aims to provide a profile of amino acid changes in the serum of patients with early-onset coronary artery disease (EOCAD) and identify potential disease biomarkers. Methods: Ultra-performance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry (UPLC-MRM-MS/MS) was used to determine the amino acid profile of patients with EOCAD in sample pools. In the validation stage, the serum levels of candidate amino acids of interest are determined for each sample. Results: A total of 128 EOCAD patients and 64 healthy controls were included in the study. Eight serum amino acids associated with disease state were identified. Compared with the control group, serum levels of seven amino acids (L-Arginine, L-Methionine, L-Tyrosine, L-Serine, L-Aspartic acid, L-Phenylalanine, and L-Glutamic acid) increased and one (4-Hydroxyproline) decreased in the patient group. Results from the validation stage demonstrate that serum levels of 4-Hydroxyproline were significantly lower in myocardial infarction (MI) patients (9.889 ± 3.635 µg/mL) than those in the controls (16.433 ± 4.562 µmol/L, p < 0.001). Elevated serum 4-Hydroxyproline levels were shown to be an independent protective factor for MI (OR = 0.863, 95% CI: 0.822-0.901). The significant negative correlation was seen between serum 4-Hydroxyproline levels and cardiac troponin I (r = -0.667) in MI patients. Conclusion: We have provided a serum amino acid profile for EOCAD patients and screened eight disease state-related amino acids, and we have also shown that 4-Hydroxyproline is a promising target for further biomarker studies in early-onset MI.


Assuntos
Aminoácidos/sangue , Doença da Artéria Coronariana/sangue , Fatores de Risco de Doenças Cardíacas , Adulto , Idade de Início , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Medição de Risco , Espectrometria de Massas em Tandem/métodos
7.
Nutr Metab Cardiovasc Dis ; 31(5): 1467-1476, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33744039

RESUMO

BACKGROUND AND AIMS: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI). METHODS AND RESULTS: The analysis included 2329 Dutch post-MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002-2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m2). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR<60; 0.90, -0.09; 1.89). Weaker, non-significant associations with kidney function decline were observed for the other plasma FAs. CONCLUSION: Higher plasma LA may be a good predictor of less kidney function decline after MI, particularly in patients with diabetes. The Alpha Omega Cohort is registered with clinicaltrials.gov, NCT03192410.


Assuntos
Ácidos Graxos/sangue , Taxa de Filtração Glomerular , Rim/fisiopatologia , Infarto do Miocárdio/complicações , Insuficiência Renal Crônica/complicações , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Países Baixos , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
Medicine (Baltimore) ; 100(3): e23468, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545927

RESUMO

BACKGROUND: The G0/G1 switch 2 (G0S2) gene is closely related to lipolysis, cell proliferation, apoptosis, oxidative phosphorylation, and the development of a variety of tumors. The aim of the present study was to expand the sample size to confirm the relationship between the expression of the G0S2 gene in peripheral blood and acute myocardial infarction (AMI) based on previous gene chip results. METHODS: Three hundred patients were initially selected, of which 133 were excluded in accordance with the exclusion criteria. Peripheral blood leukocytes were collected from 92 patients with AMI and 75 patients with stable coronary atherosclerotic disease (CAD). mRNA expression levels of G0S2 in peripheral blood leukocytes was measured by RT-PCR, and protein expression levels by Western blot analysis. The results of these assays in the 2 groups were compared. RESULTS: mRNA expression levels of GOS2 in the peripheral blood leukocytes of patients with AMI were 0.41-fold lower than those of patients with stable CAD (P < .05), and GOS2 protein expression levels were 0.45-fold lower. Multivariate logistic regression analysis indicated that low expression levels of the G0S2 gene increased the risk of AMI by 2.08-fold in stable CAD patients. CONCLUSIONS: G0S2 gene expression in the peripheral blood leukocytes of AMI patients was lower than that of stable CAD patients. Low G0S2 gene expression in peripheral blood leukocytes is an independent risk factor for AMI in stable CAD patients.


Assuntos
Proteínas de Ciclo Celular/genética , Doença da Artéria Coronariana , Infarto do Miocárdio/genética , Estudos de Casos e Controles , Proteínas de Ciclo Celular/sangue , Feminino , Expressão Gênica , Marcadores Genéticos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , RNA Mensageiro/sangue , RNA Mensageiro/metabolismo , Estudos Retrospectivos
9.
Am J Cardiol ; 146: 1-7, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33539858

RESUMO

Comparisons of the outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA) and patients with nonobstructive coronary artery disease (CAD) without myocardial infarction (MI) are limited. Here we compare the outcomes of patients with MINOCA and patients with nonobstructive CAD without MI and assess the influence of medical therapy on outcomes in these patients. Veterans who underwent coronary angiography between 2008 to 2017 with nonobstructive CAD were divided into those with or without pre-procedural troponin elevation. Patients with prior revascularization, heart failure, or who presented with cardiogenic shock, STEMI, or unstable angina were excluded. After propensity matching, outcomes were compared between groups. The primary outcome was major adverse cardiovascular events (MACE: mortality, myocardial infarction, and revascularization) within one year: 3,924 patients with nonobstructive CAD and a troponin obtained prior to angiography were identified (n=1,986 with elevated troponin) and restricted to 1,904 patients after propensity-matching. There was a significantly higher risk of MACE among troponin-positive patients compared with those with a negative troponin (HR 2.37; 95% CI, 1.67 to 3.34). Statin (HR 0.32; 95% CI, 0.22 to 0.49) and ACE inhibitor (HR 0.49; 95% CI, 0.32 to 0.75) therapy after angiography was associated with decreased MACE, while P2Y12 inhibitor, calcium-channel and beta-blocker therapy were not associated with outcomes. In conclusion, Veterans with MINOCA are at increased risk for MACE compared with those with nonobstructive CAD and negative troponin at the time of angiography. Specific medications were associated with a reduction in MACE, suggesting an opportunity to explore novel approaches for secondary prevention in this population.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Infarto do Miocárdio/etiologia , Sistema de Registros , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Troponina/sangue
10.
Nutr Metab Cardiovasc Dis ; 31(4): 1016-1026, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33612380

RESUMO

AIM: Bilirubin has potential predictive and prognostic value for myocardial infarction (MI), but the clinical evidence remains controversial. We performed this meta-analysis to systematically quantify the relationships between circulating bilirubin levels and the incidence of MI and post-MI adverse events. DATA SYNTHESIS: We searched the PubMed, Cochrane Library, Embase, and Web of Science databases for ad-hoc studies, published up to October 17, 2020, recording bilirubin before MI (predictive analyses) or adverse events (prognostic analyses). Relative risks (RR) were pooled by a random-effects model. The dose-response analysis was conducted by restricted cubic splines. In patients without previous MI, increased total bilirubin (TB) reduced the risk of long-term (>3 year) first MI by 22% (95% confidence interval [CI]: 0.69-0.88, n = 4). The dose-response analysis indicated that the RR for first MI decreased by 2.7% per each 2 µmol/L increment of TB (three studies, 95% CI: 1.3%-4.1%, P < 0.001), with a cut-off value of 12.60 µmol/L for RR > 1.00. Elevated bilirubin reduced the incidence of first and recurrent MI by 36% (95% CI: 0.42-0.98, n = 7). However, after suffering MI, higher TB concentrations could not decrease the risk of recurrent MI (RR: 1.02, 95% CI: 0.67-1.55, n = 5) and increased the incidence of short-term (<1 year) post-MI major adverse cardiovascular events, all-cause mortality, and cardiovascular mortality, but not long-term (≥1 year). CONCLUSION: Higher TB levels within a physiological range reduced the incidence of long-term first MI, with a cut-off value of 12.60 µmol/L.


Assuntos
Bilirrubina/sangue , Infarto do Miocárdio/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco , Regulação para Cima
11.
Nutr Metab Cardiovasc Dis ; 31(3): 880-885, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33546945

RESUMO

BACKGROUND AND AIMS: It remains unclear whether serum PCSK9 levels can predict the severity of the disease and the risk of future events in patients with coronary artery disease (CAD). We aimed to evaluate the association between PCSK9 levels, metabolic parameters, severity of CAD on coronary angiography (SYNTAX score), and the risk of in-hospital events and at one-year follow-up. METHODS AND RESULTS: From September 2015 to December 2016, serum PCSK9 levels were measured on admission in patients not previously receiving statin therapy, and admitted for an acute myocardial infarction (MI), in an intensive care unit from a university hospital. In a total of 648 patients (mean age: 66 years, 67% male), median PCSK9 was 263 ng/ml, higher for females compared with males (270 vs 256 ng/ml, p = 0.009). Serum PCSK9 was associated with LDL cholesterol (r = 0.083, p = 0.036), total cholesterol (r = 0.136, p = 0.001) and triglycerides (r = 0.137, p = 0.001). A positive association was also observed in the subgroup of patients with CRP >10 mg/L (p < 0.001), but not with NT-proBNP, troponin and creatine kinase. PCSK9 levels were similar whatever the SYNTAX score or the number of significant coronary lesions. PCSK9 levels were not associated with in-hospital events (death, recurrent MI and stroke) and events (cardiovascular death, cardiovascular events, recurrent MI) at one-year follow-up. CONCLUSIONS: In this large cohort of patients hospitalized for acute MI and not previously receiving statin therapy, PCSK9 levels was not associated with the severity or the recurrence of cardiovascular events. The clinical utility of measuring PCSK9 levels for this category of patients therefore appears limited.


Assuntos
Infarto do Miocárdio/sangue , Pró-Proteína Convertase 9/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Angiografia Coronária , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Recidiva , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
12.
Med Sci Monit ; 27: e928864, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635854

RESUMO

BACKGROUND Although progranulin was recently proposed as an adipokine that may be involved in glucose metabolic and inflammatory diseases, the role of serum progranulin in cardiovascular disease is elusive and remains disputed. The aim of our research was to determine the concentration of serum progranulin in Chinese patients with cardiovascular disease, notably in acute myocardial infarction (AMI), and its relationship to other cardiometabolic risk factors. MATERIAL AND METHODS This prospective observational study included 342 Chinese AMI patients and 255 healthy control subjects. Serum progranulin concentrations and various cardiometabolic risk factor levels were investigated. We assessed the relationship between progranulin and other cardiometabolic risk factors. Logistic regression analysis was applied to evaluate risk factors in patients with AMI. RESULTS Progranulin levels were obviously elevated in AMI patients compared to control subjects (P=0.0001). Correlation analysis showed that progranulin levels were positively associated with coronary artery disease severity (r=0.380, P=0.0001), glucose (r=0.195, P=0.015), and myeloperoxidase (r=0.198, P=0.014). In logistic regression analysis, serum progranulin (Exp(B)=1.104, 95% CI=1.043-1.168, P=0.001), myeloperoxidase (Exp(B)=1.006, 95% CI=1.003-1.008, P=0.0001), and uric acid (Exp(B)=1.020, 95% CI=1.009-1.032, P=0.0001) were independent risk factors in AMI patients. CONCLUSIONS Patients with AMI had significantly higher serum progranulin concentrations than control subjects. This study suggests that serum progranulin is an independent risk predictor in Chinese patients with AMI.


Assuntos
Infarto do Miocárdio/sangue , Progranulinas/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
14.
Am J Cardiol ; 147: 129-136, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617816

RESUMO

Cardiac Troponin (hs-TnT) elevation has been reported in unselected patients hospitalized with COVID-19 however the mechanism and relationship with mortality remain unclear. Consecutive patients admitted to a high-volume intensive care unit (ICU) in London with severe COVID-19 pneumonitis were included if hs-TnT concentration at admission was known. Kaplan-Meier survival analysis performed, with cohorts classified a priori by multiples of the upper limit of normal (ULN). 277 patients were admitted during a 7-week period in 2020; 176 were included (90% received invasive ventilation). hs-TnT at admission was 16.5 (9.0 to 49.3) ng/L, 56% had concentrations >ULN. 56 patients (31.8%) died during the index admission. Admission hs-TnT level was lower in survivors (12.0 (8.0-27.8) vs 28.5 (14.0 to 81.0) ng/L, p = 0.001). Univariate predictors of mortality were age, APACHE-II Score and admission hs-TnT (HR 1.73, p = 0.007). By multivariate regression, only age (HR 1.33, CI: 1.16.to 1.51, p < 0.01) and admission hs-TnT (HR 1.94, CI: 1.22 to 3.10, p = 0.006) remained predictive. Survival was significantly lower when admission hs-TnT was >ULN (log-rank p-value<0.001). Peak hs-TnT was higher in those who died but was not predictive of death after adjustment for other factors. In conclusion, in critically ill patients with COVID-19 pneumonitis, the hs-TnT level at admission is a powerful independent predictor of the likelihood of surviving to discharge from ICU. In most cases, hs-TnT elevation does not represent major myocardial injury but acts as a sensitive integrated biomarker of global stress. Whether stratification based on admission Troponin level could be used to guide prognostication and management warrants further evaluation.


Assuntos
COVID-19/epidemiologia , Cuidados Críticos , Hospitalização/estatística & dados numéricos , Infarto do Miocárdio/sangue , Troponina T/sangue , Biomarcadores/sangue , Comorbidade , Feminino , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , SARS-CoV-2
15.
JAMA Netw Open ; 4(2): e2037930, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620444

RESUMO

Importance: Chest pain is among the most common reasons for emergency department (ED) presentations. However, most patients are at low risk for acute coronary syndrome (ACS), with low cardiac adverse outcomes rates. Biomarker testing with troponin levels is key in the initial assessment for ACS. Although serial troponin testing can improve the diagnosis of ACS in clinical practice, some patients deemed to be low risk are discharged after a single negative troponin test result. Objective: To report the clinical outcomes of patients discharged after a single negative troponin test result compared with patients discharged after serial troponin measurements. Design, Setting, and Participants: This is a retrospective cohort study of ED encounters from May 5, 2016, to December 1, 2017, across 15 community EDs within an integrated health care system in southern California. The study cohort includes 27 918 adult ED encounters in which patients were evaluated for suspected ACS with a HEART (history, electrocardiogram, age, risk factors, and troponin) score and an initial conventional troponin-I measurement below the level of detection (<0.02 ng/mL). Statistical analysis was performed from December 1, 2019, to December 1, 2020. Exposure: Single troponin test vs multiple troponin tests. Main Outcomes and Measures: The primary outcome was acute myocardial infarction or cardiac mortality; secondary outcomes included coronary artery bypass graft, percutaneous coronary intervention, invasive coronary angiography, and unstable angina within 30 days of discharge. A multivariable logistic regression model was performed to evaluate the association between testing strategies and clinical outcomes. Results: A total of 27 918 patient encounters (16 212 women [58.1%]; mean [SD] age, 58.7 [15.2] years) were included in the study. Of patients with an initial troponin measurement below the level of detection, 14 459 (51.8%) were discharged after a single troponin measurement, and 13 459 (48.2%) underwent serial troponin tests. After adjustment for cardiac risk factors and comorbidities, there was no statistically significant difference in the primary outcome of acute myocardial infarction or cardiac mortality within 30 days between the 2 groups (single troponin, 56 [0.4%] vs serial troponin, 52 [0.4%]; adjusted odds ratio, 1.41 [95% CI, 0.96-2.07]). Patients discharged after a single troponin test had lower rates of coronary artery bypass graft (adjusted odds ratio, 0.24 [95% CI, 0.11-0.48]) and invasive coronary angiography (adjusted odds ratio, 0.46 [95% CI, 0.38-0.56]). Conclusions and Relevance: This study suggests that patients are routinely discharged from the ED after a single negative troponin test result, and when compared with serial troponin testing, a single troponin test appears safe based on current physician decision-making, with no difference in rates of 30-day cardiac mortality and acute myocardial infarction, which are low in both groups.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Tomada de Decisão Clínica , Cardiopatias/mortalidade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Angina Instável/epidemiologia , Angiografia Coronária/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Razão de Chances , Alta do Paciente , Intervenção Coronária Percutânea/estatística & dados numéricos , Medição de Risco
16.
JAMA ; 325(6): 552-560, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560322

RESUMO

Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019. Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy. Main Outcomes and Measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome. Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups. Conclusions and Relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm. Trial Registration: ClinicalTrials.gov Identifier: NCT02648113.


Assuntos
Anemia/terapia , Transfusão de Sangue , Infarto do Miocárdio/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Hemoglobinas/análise , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações
17.
Clin Biochem ; 91: 1-8, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33610525

RESUMO

The measurement of cardiac troponin (cTn) by a high sensitivity method now represents the standard method for cTn measurement in the laboratory. High sensitivity method are not measuring a novel form of troponin but have undergone methodological improvement in assay sensitivity to allow both very low level detection and repeat measurements at low levels with very low degrees of analytical imprecision. The methods identify additional patients with myocardial injury who would benefit from evidence-based interventions. Rapid predictive algorithms utilising measurement on admission as well as short sampling periods (1-2 h) allow much more rapid categorisation of patients to appropriate clinical pathways. The shift in the diagnosis from traditional "cardiac enzymes" to troponin based on the 99th percentile has accounted for the majority of the detection of myocardial injury in patients without acute coronary syndromes. These patients have a worse prognosis irrespective of the underlying cause of their hospital admission. The appropriate management strategy in this group, beyond managing the underlying problem, remains to be defined. Measurement of cTn in otherwise asymptomatic individuals may have a role for patient selection for preventive treatment or for patients monitoring. Clinical trials in this area are awaited.


Assuntos
Síndrome Coronariana Aguda , Algoritmos , Infarto do Miocárdio , Troponina C/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Biomarcadores/sangue , Humanos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico
18.
Clin Biochem ; 91: 16-25, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33636187

RESUMO

BACKGROUND: Combining high-sensitivity cardiac troponin (hs-cTn) with estimated glomerular filtration rate and glucose within the Clinical Chemistry Score (CCS) could help in the assessment of patients with suspected acute myocardial infarction (AMI). METHODS: In patients presenting with suspected AMI to the emergency department, we aimed to externally validate the performance of the CCS in a prospective international multicenter study and to directly compare the diagnostic and prognostic performance of the CCS with hs-cTnT and hs-cTnI baseline levels alone using a single cut-off approach. The diagnostic endpoint was diagnostic accuracy for AMI as centrally adjudicated by two independent cardiologists including cardiac imaging and serial hs-cTnT/I measurements. The prognostic endpoint was 30-day AMI or death. RESULTS: AMI was the final diagnosis in 620/3827 patients (16.2%) adjudicated with hs-cTnT and 599 patients (15.7%) adjudicated with hs-cTnI. The CCS resulted in high diagnostic accuracy for AMI and prognostic accuracy for 30-days AMI/death as quantified by the area under the receiver-operating characteristic curve (AUC), using hs-cTnT 0.90 (95%CI 0.89-0.91) and 0.89 (95%CI 0.88-0.90), using hs-cTnI 0.91 (95%Cl 0.90-0.92) and 0.90 (95%CI 0.89-0.91) respectively. E.g. a CCS of 0 points resulted in a sensitivity of 99.8% (95%CI 99.1-100%) for rule-out of index AMI and 99.5% (95%CI 98.5-100%) for AMI/death at 30 days for hs-cTnT and 99.8% (95%CI 98.9-100%) and 99.6% (95%CI 98.6-100%) using hs-cTnI. Overall, the single hs-cTnT/I measurement approach provided comparable diagnostic (sensitivity 99.5-99.7%) and prognostic (sensitivity 98.9-99.5%) performance versus the CCS. INTERPRETATION: The CCS provided high diagnostic and prognostic performance also in this independent large validation cohort. A single hs-cTnT/I measurement approach for rule-out MI yielded similar estimates.


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Troponina C/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
19.
Am Heart J ; 234: 60-70, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33460579

RESUMO

BACKGROUND: CODE-MI is a pan-Canadian, multicentre, stepped-wedge, cluster randomized trial that evaluates the impact of using the female-specific 99th percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department (ED) with symptoms suggestive for myocardial ischemia. A feasibility study was conducted to estimate the number of eligible patients, the rate of the study's primary outcome under control conditions, and the statistical power to detect a clinically important difference in the primary outcome. METHODS: Using linked administrative data from 11 hospitals in Ontario, Canada, from October 2014 to September 2017, the following estimates were obtained: number of women presenting to the ED with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (ie, primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. RESULTS: Overall, 2,073,849 ED visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. CONCLUSIONS: This feasibility study greatly enhanced the design of CODE-MI, allowed accurate evaluation of the study power, and demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina/sangue , Dor no Peito/etiologia , Estudos de Coortes , Dispneia/etiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Ontário/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea , Projetos de Pesquisa , Fatores Sexuais , Avaliação de Sintomas , Resultado do Tratamento
20.
Medicine (Baltimore) ; 100(1): e23949, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429753

RESUMO

BACKGROUND: The sensitivity and specificity of the routine detection of acute myocardial infarction (AMI) in early diagnosis are not high, which can not meet the clinical needs. Copeptin combined with hypersensitive cardiac troponin T (hs-cTnT) is a new detection scheme, and its value in the early diagnosis of acute myocardial infarction is still unclear. Accordingly, the aim of this study is to evaluate the diagnostic value of copeptin combined with hypersensitive troponin T detection in early acute myocardial infarction. METHODS: This is a prospective, randomized; double-blind diagnostic trial to investigate the diagnostic value of copeptin combined with hypersensitive troponin T detection in early acute myocardial infarction. Approved by the clinical research ethics of our hospital. Patients were randomly divided into one of 2 test protocols: (A) copeptin combined with hs-cTnT group and (B) cardiac troponin I (cTnI) group. Patients, doctors, nurses, inspectors, and data-gathering assistants were blinded to group allocation. We will focus on the sensitivity comparison of the 2 detection methods at different time periods and the sensitivity and specificity comparison of the two detection methods. Data were analyzed using the statistical software package SPSS version 25.0 (Chicago, IL). DISCUSSION: The purpose of this study is to evaluate the diagnostic value of copeptin combined with hypersensitive cardiac troponin T detection in early acute myocardial infarction. The results of this study will establish clinical evidence for the detection of high sensitivity cardiac troponin T in the early diagnosis of acute myocardial infarction. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6TE5Z.


Assuntos
Protocolos Clínicos , Glicopeptídeos/análise , Infarto do Miocárdio/diagnóstico , Troponina T/análise , Biomarcadores/análise , Biomarcadores/sangue , Método Duplo-Cego , Glicopeptídeos/sangue , Humanos , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Troponina T/sangue
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