RESUMO
High-density lipoproteins' (HDL) stability is a determinant of their residence times in plasma and consequently an important parameter that influences the beneficial properties of these lipoproteins. Since there are no accessible procedures for this purpose, here, we describe the methodological conditions to assess the stability of the HDL based on the redshift of the fluorescence spectrum of tryptophans contained in the structure of HDL-apolipoproteins during incubation with urea 8M. Along the HDL denaturation kinetics, the main variations of fluorescence were observed at the wavelengths of 330, 344, and 365 nm at room temperature. Therefore, HDL denaturation was estimated using the tryptophan (Trp)-ratio of fluorescence intensity (rfi) at such wavelengths. By setting 100% of the measurable denaturation at 26 h, HDL reached 50% after 8 h of incubation with urea. Then, for further analyses we determined the percentage of HDL denaturation at 8 h as an estimation of the stability of these lipoproteins. To explore the potential usefulness of this test, we analyzed the stability of HDL isolated from the plasma of 24 patients diagnosed with acute coronary syndrome (ACS). These HDL presented significantly higher percentages of denaturation (64.9% (58.7-78.4)) than HDLs of healthy individuals (23.3% (20.3-27.0)). These results indicate that HDL in ACS are less stable than in control subjects. Moreover, the percentage of denaturation of HDL correlated with body mass index and aspartate transaminase plasma activity. Furthermore, apo-I, HDL-cholesterol, HDL-triglycerides, and apo A-I-to-triglycerides ratio correlated with the percentage of HDL denaturation, suggesting that the lipoprotein composition is a main determinant of HDL stability. Finally, the percentage of HDL denaturation is the parameter that predicted the presence of ACS as determined by a machine learning procedure and logistic regression analysis. In conclusion, we established the methodological conditions to assess the stability of HDL by a fluorescence-based method that merits exploration in prospective studies for evaluating the coronary artery disease risk.
Assuntos
Síndrome Coronariana Aguda/patologia , Fluorescência , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Triptofano/química , Síndrome Coronariana Aguda/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desnaturação Proteica , Estabilidade ProteicaRESUMO
Dyslipidemia has a substantial role in the development of acute coronary syndrome (ACS). Previous reports, including genome-wide associations studies (GWAS), have shown that some genetic variants of the proprotein convertase subtilisin-kexin type 7 (PCSK7) gene are associated with plasma lipid levels. In the present study, we evaluated whether PCSK7 gene polymorphisms are significantly associated with the plasma lipid profile and ACS. Three PCSK7 gene polymorphisms (rs508487 T/C, rs236911 C/A, and rs236918 C/G) were determined using TaqMan genotyping assays in a group of 603 ACS patients and 622 healthy controls. The plasma lipid profile was determined in the study groups by enzymatic/colorimetric assays. Under the recessive model, the rs236918 C allele was associated with a high risk of ACS (OR = 2.11, pC = 0.039). In the same way, under the recessive and additive models, the rs236911 C allele was associated with a high risk of ACS (OR = 1.95, pC = 0.037, and OR = 1.28, pC = 0.037, respectively). In addition, under the co-dominant model, the rs508487 T allele was associated with a higher risk of ACS (OR = 1.78, pC = 0.010). The CCC and TCC haplotypes were associated with a high risk of ACS (OR = 1.21, pC = 0.047, and OR = 1.80, pC = 0.001, respectively). The rs236911 CC and rs236918 CC genotypes were associated with lower high-density lipoproteins-cholesterol (HDL-C) plasma concentrations, whereas the rs236911 CC genotype was associated with a higher concentration of triglycerides, as demonstrated in the control individuals who were not receiving antidyslipidemic drugs. Our data suggest that the PCSK7 rs508487 T/C, rs236911 C/A, and rs236918 C/G polymorphisms are associated with the risk of developing ACS, and with plasma concentrations of HDL-C and triglycerides.
Assuntos
Síndrome Coronariana Aguda , HDL-Colesterol/sangue , Dislipidemias , Subtilisinas/genética , Triglicerídeos/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/metabolismo , Idoso , Estudos de Casos e Controles , Dislipidemias/genética , Dislipidemias/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Acute coronary syndrome (ACS) is the leading cause of death in elderly patients worldwide. Due its participation in apoptosis, fibrosis, and angiogenesis, transforming growth factor-ß (TGF-ß) isoforms had been categorized as risk factors for cardiovascular diseases. However, due their contradictory activities, a cardioprotective role has been suggested. The aim was to measure the plasma levels of TGF-ß1, 2, and 3 proteins in patients with ACS. This was a case-control study including 225 subjects. The three activated isoforms were measured in serum using the Bio-Plex Pro TGF-ß assay by means of magnetic beads; the fluorescence intensity of reporter signal was read in a Bio-Plex Magpix instrument. We observed a significant reduction of the three activated isoforms of TGF-ß in patients with ACS. The three TGF-ß isoforms were positively correlated with each other in moderate-to-strong manner. TGFß-2 was inversely correlated with glucose and low-density lipoprotein (LDL)-cholesterol, whereas TGF-ß3 was inversely correlated with the serum cholesterol concentration. The production of TGF-ß1, TGF-ß2, and TGF-ß3 are decreased in the serum of patients with ACS. Further follow-up controlled studies with a larger sample size are needed, in order to test whether TGF-ß isoforms could be useful as biomarkers that complement the diagnosis of ACS.
Assuntos
Síndrome Coronariana Aguda/patologia , Fator de Crescimento Transformador beta/sangue , Síndrome Coronariana Aguda/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/sangue , Isoformas de Proteínas/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Introducción: La Troponina I (TnI) plasmática es el biomarcador "Gold" estándar utilizado en diagnóstico de Infarto Agudo al Miocardio (IAM), indicando necrosis cardíaca. Las microvesículas extracelulares (MVEC), participan en comunicación celular, por lo que estudiar su distribución entregaría información respecto del evento isquémico, antesala del infarto. Objetivo: Estudiar las MVECs plasmáticas en pacientes con Síndrome Coronario Agudo (SCA) y compararlas con los niveles de TnI. Métodos: Plasma de 22 pacientes controles se recolectó 0-2hrs post-ingreso a urgencia. Plasma de 45 pacientes SCA se recolectó 0-2, 6-8 y 10-14hrs post ingreso, junto con la toma de muestra para estudio de TnI. Las MVECs plasmáticas fueron enriquecidas mediante kit comercial. La determinación de la concentración y tamaño MVECs se realizó por NTA (Nanoparticles Tracking Assay) usando el equipo Nanosight. Resultados: La concentración promedio de MVECs 0-2 hrs post ingreso fue 7,2 veces superior en plasma de pacientes con SCA vs controles y la moda del tamaño disminuyó en pacientes con SCA. La TnI no mostró diferencias significativas en 0-2 hrs post ingreso en el grupo estudiado. La concentración de las MVEC disminuyó significativamente después de 10-14 hrs post ingreso, mientras que la concentración promedio TnI se mantuvo invariable demostrando el aumento de MVECs previo al incremento de TnI. Conclusión. El aumento de MVECs previo al incremento de la TnI en pacientes infartados, sugiere que las MVECs aumentan en la fase previa del IAM, como respuesta al daño tisular. Actualmente, estudiamos el contenido molecular de las MVECs, para establecer un método diagnóstico del Síndrome Coronario Agudo basado en MVECs.
Background: Troponin I (TnI) is the gold standard used to establish the diagnosis of myocardial infarction (AMI), indicating the presence of myocardial necrosis. Extracellular micro vesicles are involved in cellular communication. Their distribution may provide information relating to the development of AMI in patients with acute coronary syndromes (ACS) Aim: to study plasma levels of ECMV compared to those of TnI in patients with ACS. Methods: The plasma levels of TnI and ECMV from 22 control patients coming to the emergency units was compared to plasma from 45 patients with ACS. Levels of both parameters were determined 0-2, 6-8 and 10-14 hours post admission. ECMVs were enriched by means of a commercial kit. Concentration and size of ECMV was determined by NTA (Nanoparticles tracking assay) using the Nanosight equipment. Results: Plasma concentration of ECMV was 7.2 times higher than that of TnI 0-2 hrs post admission. The mode of ECMV size was lower in patients with ACS. Concentration of ECMV had decreased significantly 10-14 hrs post admission, whereas the TnI levees remained stable. Conclusion: The increase in ECMV earlier than TnI in AMI suggests that ECMV are elevated in the pre-AMI phase, as a response to early tissue damage. A study of cellular content of ECMV, being carried out, may lead to develop a method for the early diagnosis of AMI in patients with ACS.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Vesículas Extracelulares/fisiologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/metabolismo , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/metabolismo , Análise de Variância , Biomarcadores/sangue , Rastreamento de Células/métodos , Exossomos/fisiologia , NanopartículasRESUMO
UNLABELLED: Psychosocial factors have been linked to cardiovascular diseases independently of traditional risk factors. The impact of psychosocial factors on plaque destabilizing factors, such as matrix metalloproteinases (MMPs) has been proposed although scarcely studied. OBJECTIVE: To evaluate the relationships between hostility, perceived stress and social support with MMPs activity in patients after an Acute Myocardial Infarction (AMI). METHODS: Blood samples were obtained from 76 patients on admission, post-angioplasty, 24h, 7 days and 3 months after AMI. Hostility, perceived stress and social support were evaluated by validated questionnaires. RESULTS: Social support was positively correlated with patients ejection fraction (r=0.453, p=0.009). Patients with higher infarct size presented increased MMP-2 activity at admission (p=0.04). Patients with one diseased vessel had more social support than those with three diseased vessels (p=0.05). The highest values of MMP-2 and MMP-9 activity were observed at the acute event, decreasing, with the lowest activity at 3 months post-AMI (p<0.001). Only in patients with low social support, hostility correlated with MMP-2 activity, from AMI onset (r=0.645, p=0.013), to 7 days post AMI (r=0.557, p=0.038). Hostility explained up to 28% of the variance in MMP-2 activity (R(2)=0.28, p=0.005). Finally, in patients with high hostility, MMP-9 was positively correlated with IL-1ß (r=0.468, p=0.02). CONCLUSIONS: This study adds weight to the idea that two psychosocial factors, namely hostility and social support, acting jointly, may affect MMP-2 activity. Moreover, in hostile patients, there is a link between IL-1ß and MMP-9. These findings support the role of psychosocial factors in plaque destabilization and in the inflammatory process in AMI.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Hostilidade , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Apoio Social , Estresse Psicológico/metabolismo , Síndrome Coronariana Aguda/psicologia , Síndrome Coronariana Aguda/terapia , Idoso , Angioplastia Coronária com Balão , Proteína C-Reativa/metabolismo , Estudos de Coortes , Creatina Quinase/metabolismo , Creatina Quinase Forma MB/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Interleucina-1beta/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Pessoa de Meia-Idade , Infarto do Miocárdio/psicologia , Infarto do Miocárdio/terapia , Estudos Prospectivos , Estresse Psicológico/psicologiaRESUMO
BACKGROUND: Microalbuminuria is a known risk factor for cardiovascular morbidity and mortality suggesting that it should be a marker of endothelial dysfunction. Albumin to creatinine ratio (ACR) is an available and rapid test for microalbuminuria determination, with a high correlation with the 24-h urine collection method. There is no prospective study that evaluates the prognostic value of ACR in patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS). The purpose of our study was to detect the long-term prognostic value of ACR in patients with NSTE-ACS. METHODS: Albumin to creatinine ratio was estimated in 700 patients with NSTE-ACS at admission. Median follow-up time was 18 months. The best cutoff point of ACR for death or acute myocardial infarction was 20 mg/g. Twenty-two percent of patients had elevated ACR. RESULTS: By multivariable Cox regression analysis, ACR was an independent predictor of the clinical endpoint: odds ratio 5.8 (95% confidence interval [CI] 2-16), log-rank 2 p < 0.0001 in a model including age > 65 years, female gender, diabetes mellitus, creatinine clearance, glucose levels at admission, elevated cardiac markers (troponin T/CK-MB) and ST segment depression. The addition of ACR significantly improved GRACE score C-statistics from 0.69 (95% CI 0.59-0.83) to 0.77 (95% CI 0.65-0.88), SE 0.04, 2 p = 0.03, with a good calibration with both models. CONCLUSIONS: Albumin to creatinine ratio is an independent and accessible predictor of long-term adverse outcomes in NSTE-ACS, providing additional value for risk stratification.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Albuminúria/urina , Creatinina/urina , Eletrocardiografia , Medição de Risco/métodos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/epidemiologia , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Argentina/epidemiologia , Biomarcadores/urina , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001). CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Endotelina-1/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/metabolismo , Idoso , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Imunoensaio de Fluorescência por Polarização , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Estatística como Assunto , TunísiaRESUMO
BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001. CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Endotelina-1/sangue , Hiper-Homocisteinemia/metabolismo , Síndrome Coronariana Aguda/metabolismo , Homocisteína/sangue , Espectrometria de Massas , Tunísia , Estudos de Casos e Controles , Fatores Sexuais , Estudos Prospectivos , Fatores de Risco , Estatística como Assunto , Imunoensaio de Fluorescência por Polarização , Cromatografia Líquida de Alta PressãoRESUMO
Background: Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events. Objective: To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days. Methods: Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test (Armitage) were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of <10% were submitted to multiple logistic regression model. Results: A total of 457 patients with a mean age of 62.1 years, of whom 63.7% were males, were included. Risk factors such as hypertension (85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics. In the evaluation of events at 180 days, there were 28 deaths (6.2%). The statistical analysis showed that the variables that interfered with troponin elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016). The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77. Conclusion: This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this ...
Fundamento: A doença cardiovascular é a maior causa de mortalidade no mundo ocidental, devendo seu tratamento ser otimizado, para a redução de eventos adversos graves. Objetivo: Determinar o efeito do uso prévio de inibidores da enzima de conversão da angiotensina na mensuração da troponina I cardíaca em pacientes com síndrome coronariana aguda sem supradesnivelamento do segmento ST (SCASST), e avaliar os desfechos clínicos em até 180 dias. Métodos: Estudo prospectivo, observacional, em um centro terciário, em pacientes com síndrome coronariana aguda sem supradesnivelamento do segmento ST (SCASST). Foram analisadas variáveis clínicas, eletrocardiográficas e laboratoriais, com ênfase no uso prévio de inibidores da enzima de conversão da angiotensina e dosagem de troponina I cardíaca. Foram usados os testes qui quadrado de Pearson ou exato de Fischer , além do teste não paramétrico de Mann-Whitney. Variáveis com níveis de significância < 10% foram submetidas a modelo de regressão logística múltipla. Resultados: Incluídos 457 pacientes, com idade média de 62,1 anos, dos quais 63,7% eram do sexo masculino. Fatores de risco como hipertensão arterial sistêmica (85,3%) e dislipidemia (75,9%) foram os mais prevalentes, com 35% de diabéticos. Na avaliação de eventos em 180 dias, observaram-se 28 óbitos (6,2%). Na análise estatística, as variáveis que interferiram no aumento de troponina (> 0,5 ng/mL) foram a glicemia de admissão elevada (p = 0,0034) e o infradesnivelamento do segmento ST ≥ 0,5 mm, em uma ou mais derivações (p = 0,0016). Relacionada com troponina ≤ 0,5 ng/mL, esteve o uso de inibidores da enzima de conversão da angiotensina prévio à internação (p = 0,0482). ...
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Troponina I/análise , Síndrome Coronariana Aguda/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Biomarcadores/análise , Coração/efeitos dos fármacos , Hospitalização , Modelos Logísticos , Estudos Prospectivos , Valores de Referência , Medição de Risco , Fatores de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events. OBJECTIVE: To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days. METHODS: Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test (Armitage) were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of <10% were submitted to multiple logistic regression model. RESULTS: A total of 457 patients with a mean age of 62.1 years, of whom 63.7% were males, were included. Risk factors such as hypertension (85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics. In the evaluation of events at 180 days, there were 28 deaths (6.2%). The statistical analysis showed that the variables that interfered with troponin elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016). The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77. CONCLUSION: This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Troponina I/análise , Síndrome Coronariana Aguda/metabolismo , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Biomarcadores/análise , Feminino , Coração/efeitos dos fármacos , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Medição de Risco , Fatores de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
Endothelial dysfunction plays an essential role in the development and progression of atherosclerotic lesions. Endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) are considered important molecules in the endothelial dysfunction process. The aim of the present study was to evaluate the role of eNOS and ET-1 (EDN1) gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS). Six polymorphisms (rs1799983, rs2070744, rs1800783, rs3087459, rs1800541, and rs5369) of eNOS and EDN1 genes were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 283 healthy controls. The results showed increased frequencies of the A allele of the END1-914 C>A (rs3087459) polymorphism in ACS patients when compared to controls (OR=1.56, Pc=0.01). Under an additive model, the "AA" genotype was associated with an increased risk of developing ACS, adjusted for gender, hypertension, dyslipidemia, alcohol consumption, smoking, and diabetes (OR=1.56, p=0.045). Linkage disequilibrium analysis showed one EDN1 haplotype (AT) with increased frequency in ACS patients when compared to healthy controls (OR=1.65, Pc=0.0015). The "AT" haplotype was associated with the risk of developing ACS after adjusting for cardiovascular risk factors using multiple logistic analysis. In this case, the adjusted OR was 1.73 for the AT haplotype (Pc=0.0018). In summary, resulting data suggest that the END1-914 C>A gene polymorphism could be involved in the risk of developing ACS in Mexican individuals.
Assuntos
Síndrome Coronariana Aguda/genética , Endotelina-1/genética , Polimorfismo de Nucleotídeo Único , Síndrome Coronariana Aguda/metabolismo , Idoso , Estudos de Casos e Controles , Dislipidemias/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genéticaRESUMO
BACKGROUND: Half of patients with acute heart failure syndromes (AHFS) have preserved left ventricular ejection fraction (PLVEF). In this setting, the role of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT), remains to be established. AIM: To evaluate the prevalence and long-term prognostic significance of cTnT elevations in patients with AHFS and PLVEF. PATIENTS AND METHODS: This retrospective, multicenter, collaborative study included 500 patients hospitalized for AHFS with PLVEF (ejection fraction ≥40%) between October 2000 and December 2006. Blood samples were collected within 12 hours after admission and were assayed for cTnT. MMD was defined as a cTnT value of ≥0.020 ng/mL. RESULTS: Mean age was 73 ± 12 years, 47% were female, 38% had an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 ± 0.7. Mean cTnT value was 0.149 ± 0.484 ng/mL, and cTnT was directly correlated with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P < .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001), higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class (P < .001), and higher natriuretic peptide levels (P < .001) as compared with patients without MMD. At 6-month follow-up, overall event-free survival was 55% and 75% in patients with and without MMD (P < .001), respectively. On multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and MMD (HR = 1.81; P = .001) were identified as predictors of events. CONCLUSIONS: Increased cTnT levels were detected in approximately 50% of patients with AHFS with preserved systolic function, and were found to correlate with clinical measures of disease severity. The presence of MMD was associated with a worse long-term outcome, lending support to cTnT-based risk stratification in the setting of AHFS.
Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Sístole/fisiologia , Troponina T/metabolismo , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Comportamento Cooperativo , Feminino , Seguimentos , Insuficiência Cardíaca/metabolismo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Síndrome , Tempo , Troponina T/biossíntese , Adulto JovemRESUMO
BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be a rapidly rising and sensitive biochemical marker especially for the diagnosis of myocardial ischemia. The aim of this study was to evaluate the influence of temperature on the capacity of cobalt binding to human albumin and the influence of this variable on IMA measurement. METHODS: The following temperatures of incubation were tested for human albumin standard 25 degrees C, 28 degrees C, 31 degrees C, 34 degrees C, and 37 degrees C and for patients with suspected acute coronary syndrome, room temperature and 37 degrees C. IMA was measured by cobalt-albumin binding assay. RESULTS: There was a strong positive correlation (r = 0.98, p < 0.001) between IMA and the assay temperatures. IMA levels were 0.68 +/- 0.25 absorbance units (ABSU) at room temperature and 0.92 +/- 0.33 ABSU (p < 0.001) at 37 degrees C in the study participants. CONCLUSIONS: IMA values were influenced by the assay temperature.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Cobalto/metabolismo , Erros de Diagnóstico/prevenção & controle , Temperatura Alta , Albumina Sérica/metabolismo , Síndrome Coronariana Aguda/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Humanos , Ligação Proteica , Sensibilidade e Especificidade , Albumina Sérica HumanaRESUMO
Currently, the wide variety of antithrombotic agents as adjunctive pharmacological therapy for non-ST-segment elevation acute coronary syndromes (ACS) in the setting of contemporary percutaneous coronary intervention (PCI) available for clinical use has made choosing the optimal drug therapy a complex and difficult task. In the stent era, bivalirudin, a semisynthetic direct thrombin inhibitor, has recently been shown to provide similar efficacy with less bleeding compared with unfractionated heparin plus platelet glycoprotein IIb/IIIa inhibitors in ACS patients treated with PCI. Although there are some controversial results and limitations in the studies with bivalirudin, this drug certainly is a plausible option in the treatment of ACS. With current findings in contemporary PCI, there may be a steady increase in the utilization of bivalirudin. On the other hand, in the real world, there may be reinforcement in the sole use of unfractionated heparin confining glycoprotein IIb/IIIa inhibitors and other intravenous antithrombotics to bailout therapy for periprocedural PCI complications in ACS patients.
Assuntos
Síndrome Coronariana Aguda/terapia , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/prevenção & controle , Heparina , Hirudinas , Fragmentos de Peptídeos , Inibidores da Agregação Plaquetária , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/metabolismo , Angioplastia Coronária com Balão/métodos , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Antitrombinas/farmacocinética , Terapia Combinada , Eletrocardiografia , Hemorragia/induzido quimicamente , Hemorragia/metabolismo , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/farmacocinética , Hirudinas/administração & dosagem , Hirudinas/efeitos adversos , Hirudinas/farmacocinética , Humanos , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/farmacocinética , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Equivalência TerapêuticaRESUMO
The acute coronary syndrome (ACS) is characterized by a spectrum of arterial diseases that include unstable angina and myocardial infarction. In the last 10 years, ACS has become the cause of up to 29% of deaths in the industrialized countries, becoming the main cause of death, and it will most probably stay that way for the year 2020. The physiopathogenesis of ACS include oxidative, inflammatory, and thrombotic processes. Diverse molecules participate in the processes, increasing of decreasing the damage. The genes that encode these molecules have been associated with the disease. However, in some cases inconsistent results in different populations have been reported. In this review the physiopathogenesis and the role of several candidate genes involved in the pathogenesis of ACS are discussed.
Assuntos
Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/metabolismo , HumanosRESUMO
INTRODUCTION: Clinical nonresponse to clopidogrel has been associated with variability in response. This has led to the development of other P2Y12 receptor inhibitors, such as prasugrel and ticagrelor, with different pharmacokinetic characteristics that influence their pharmacodynamics. AREAS COVERED: Clopidogrel response variability is attributable to its complex pharmacokinetics and is vulnerable to genetic polymorphisms in genes involved in absorption, metabolism and drug-drug interactions (i.e., proton pump inhibitors). Prasugrel which has a simpler metabolism, leading to greater bioavailability, seems to be less affected by genetic or drug-drug interactions and achieves a greater antiplatelet effect. Ticagrelor is the most novel compound approved with a simpler metabolism. Both prasugrel and ticagrelor reached their antiplatelet effect faster and to a much greater extent than clopidogrel. All these differences observed in kinetics explain, to some degree, the efficacy and safety profile observed in clinical trials for these molecules associated with other antiplatelet agents (aspirin, gpIIb/IIIa inhibitors) and anticoagulants. EXPERT OPINION: Clopidogrel is still the best standard of care. However, the pharmacokinetic advantages of both prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for the appropriate subject.
Assuntos
Adenosina/análogos & derivados , Piperazinas/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Tiofenos/farmacocinética , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/metabolismo , Adenosina/farmacocinética , Adenosina/uso terapêutico , Clopidogrel , Humanos , Piperazinas/uso terapêutico , Cloridrato de Prasugrel , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Padrão de Cuidado , Tiofenos/uso terapêutico , Ticagrelor , Ticlopidina/farmacocinética , Ticlopidina/uso terapêutico , Resultado do TratamentoRESUMO
Metabolic syndrome (MS) identifies cardiovascular risk; however, there is little information regarding the evolution of patients with MS after stent implantation. The aim of this single-center study is to evaluate the possible association between MS and clinical restenosis, after adjustment for highsensitivity C-reactive protein (hs-CRP) and angiographic predictors of restenosis. In a longitudinal study, 159 patients (89 with and 70 without MS) were studied. Criteria for MS were: elevated blood pressure (systolic >or=130 mmHg, diastolic >or=85 mmHg or drug treatment for hypertension; elevated fasting glucose (>100 mg/dl) or drug treatment for elevated glucose; reduced HDL-cholesterol (<40 mg/dl in men and <50 mg/dl in women) or drug treatment for reduced HDL-cholesterol; elevated triglycerides (>or=150 mg/dl) or drug treatment for elevated triglycerides; and obesity (body mass index >28.8 kg/m2). The primary end point was the rate of major adverse clinical events (MACE): cardiovascular death, myocardial infarction, or target lesion revascularization (TLR) during the 12-month follow-up period. The secondary end point was the rate of TLR. MS was neither identified as predictor of MACE [hazard ratio (HR): 0.844; 95% CI: 0.41-1.74; p=0.648], nor TLR (HR: 1.05; 95% CI: 0.44-2.50; p=0.91), even when controlled for hs-CRP levels and angiographic predictors of restenosis. Also, no significant interaction between MS and hs-CRP was found (p=0.135 and p=0.194, for MACE and TLR, respectively). This study shows that patients with MS do not have an additional risk of MACE, even when controlled for angiographic predictors of restenosis and hs-CRP.
Assuntos
Síndrome Coronariana Aguda/terapia , Proteína C-Reativa/metabolismo , Reestenose Coronária/complicações , Síndrome Metabólica/complicações , Stents , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/patologia , Reestenose Coronária/patologia , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , PrognósticoRESUMO
Objetivo: Descrever as características pessoais, clínicas, de tratamento, evolução para óbito e correlacionar escore TIMI ao número de internaçõesem UTI e transferência para cineangicoronariografia. Métodos: estudo prospectivo transversal empacientes internados no Hospital Nossa Senhora da Conceição em Tubarão-SC, nos períodos de novembro de 2006 a abril de 2007. Resultados: A média foi de idade de 62 anos, com predominância do sexo masculino (61,9%). Da amostrade 42 pacientes, 54,8% apresentou angina instável e 45,2%; infarto agudo do miocárdio sem supra de ST. Osfatores de risco prevalentes foram em ordem decrescente de freqüência: hipertensão arterial (78,6%),hereditariedade (57,1%), tabagismo (52,4%), dislipidemia (50%) e diabetes (38,1%). A angina prévia estava presente em 42,8% dos pacientes, o IAM em 33,3% e arevascularização miocárdica prévia em 7,1%. A maioria dos pacientes apresentou o ECG normal (35,7%) e umescore TIMI de alto, moderado e baixo risco respectivamente em 4,7%, 57,1% e 38%. Os medicamentos usados na emergência em ordem decrescente de freqüência foram: Nitrato (89,7%), AAS(87,2%), oxigênio (48,7%) e morfina (37,8%). E durante a internação os resultados foram: AAS (97,6%),clopidogrel (92,8%), nitrato (87,8%), HBPM (85,7%), IECA (78,5%), betabloqueador (54,7%), estatina (52,8%), bloqueador de cálcio (11,9%) e HNF (9,5%). O escore de TIMI foi referido no prontuário de 1 paciente apenas. Conclusão: O escore TIMI foi pouco registrado nos prontuários. A taxa de mortalidade foi inferior àapresentada pela literatura. Os IECA, estatina, o clopidogrel, a heparina e o AAS durante a internação foram bem utilizados enquanto que o AAS na admissão, o betabloqueador e a estatina podem estar sendo subutilizados. Os pacientes de alto risco pelo escoreTIMI receberam atendimento intensivo na UTI mesmo não havendo significância estatística.
Objective: to describe the personal characteristic, clinical treatment, grown to death and correlate TIMI score to ICU internment or transference to the cardiaccatheterization. Methods: Was made transversal study in intern patients of the Nossa Senhora da Conceição Hospital, between November 2006 to April 2007. Results: The mean rate of age was 62 years old, with predominance of male (61,9%). From the sample 42 patients, 54,8% showed UA and 45,2% NSTEMI. The prevalence of risk factor in decrease attendance order were: arterial hypertension (78,6%), heredity (57,1%), abusive smoking ou tabagysm (52,4%),hyperlipidemia (50%), diabetes (38,1%) The previous angine was present in 42,8% of the patients, the IAM in 33,3% and the previous miocardic revascularization in 7,1%. High, moderate and low TIMI score, respectively in 4,7%, 57,1% and 38%. The medicaments used in emergence in decrease attendance order were: Nitrate(89,7%), SAA (87,2%), Oxygen (48,7%), and Morphine (37,8%), During the internment the results were: SAA (97,6%), clopidogrel (92,8%), nitrate (87,8%), LMWH (85,7%), ACEI (78,5%), â blocker (54,7%), statin(52,8%), calcium blocker (11,9%) and HNF (9,5%). Only one patient had reference to TIMI. Conclusion: The TIMI score was little register in the medical record. The mortality rate was lower than showed in the literature. The use of de ACEI, statin, o clopidogrel, heparin and the SAA during the internmentwere used, however SAA in entrance/admission, the â blocker and a statin can be poor available. The patientswith high risk by means of TIMI score received intensive attendance in the UTI service in spite of no statistic significance.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/prevenção & controle , Síndrome Coronariana Aguda/reabilitaçãoRESUMO
BACKGROUND: Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE: This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS: A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (DeltaI30/DeltaG30). RESULTS: Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION: High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Síndrome Metabólica/metabolismo , Síndrome Coronariana Aguda/terapia , Adulto , Idoso , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/fisiologia , Masculino , Síndrome Metabólica/terapia , Pessoa de Meia-IdadeRESUMO
FUNDAMENTO: Pacientes com síndrome metabólica (SM) têm alto risco coronariano e a disfunção da célula beta ou resistência à insulina pode prever um risco adicional de eventos cardiovasculares precoces. OBJETIVO: Avaliar as alterações glicometabólicas precoces em pacientes com SM, mas sem diagnóstico de diabete tipo 2, após síndrome coronariana aguda. MÉTODOS: Um total de 114 pacientes foi submetido ao teste oral de tolerância à glicose (TOTG), 1-3 dias da alta hospitalar, após infarto agudo do miocárdio ou angina instável. Baseado no TOTG, definimos três grupos de pacientes: tolerância normal à glicose (TNG; n=26), tolerância alterada à glicose (TAG; n=39) ou diabetes mellitus (DM; n=49). O Modelo de Avaliação da Homeostase (HOMA-IR) foi usado para estimar a resistência à insulina; a responsividade da célula beta foi avaliada através do índice insulinogênico de 30 minutos (ΔI30/ΔG30). RESULTADOS: Baseado no HOMA-IR, os pacientes com DM eram mais insulino-resistentes do que aqueles com TNG ou TAG (p<0,001). De acordo com o índice insulinogênico, a responsividade da célula beta também estava alterada em indivíduos com DM (p<0,001 vs TNG ou TAG). CONCLUSÃO: Altas taxas de alterações glicometabólicas foram encontradas após síndrome coronariana aguda em pacientes com SM. Como essas anormalidades acentuadamente aumentam o risco de desfechos adversos, o TOTG precoce pode ser utilizado em pacientes com SM para identificar aqueles que apresentam maior risco coronariano.
BACKGROUND: Patients with metabolic syndrome (MetS) are at high coronary risk and beta-cell dysfunction or insulin resistance might predict an additional risk for early cardiovascular events. OBJECTIVE: This study aimed to evaluate early glucometabolic alterations in patients with MetS, but without previously known type 2 diabetes, after acute coronary syndrome. METHODS: A total of 114 patients were submitted to an oral glucose tolerance test (OGTT) 1-3 days after hospital discharge due to myocardial infarction or unstable angina. Based on the OGTT, we defined three groups of patients: normal glucose tolerance (NGT; n=26), impaired glucose tolerance (IGT; n=39), or diabetes (DM; n=49). The homeostasis model assessment (HOMA-IR) was used to measure insulin resistance; beta-cell responsiveness was assessed by the insulinogenic index at 30 min (ΔI30/ΔG30). RESULTS: Based on the HOMA-IR, patients with DM were more insulin-resistant than those with NGT or IGT (p<0.001). According to the insulinogenic index, the beta-cell responsiveness was also impaired in subjects with DM (p<0.001 vs NGT or IGT). CONCLUSION: High rates of glucometabolic alterations were found after acute coronary syndrome in patients with MetS. As these abnormalities markedly increase the risk for adverse outcomes, early OGTT among MetS patients might be used to identify those at the highest coronary risk.
FUNDAMENTO: Pacientes con síndrome metabólico (SM) tienen alto riesgo coronario y la disfunción de la célula beta o la resistencia a la insulina puede prever un riesgo adicional de eventos cardiovasculares precoces. OBJETIVO: Evaluar las alteraciones glucometabólicas precoces en pacientes con SM, pero sin diagnóstico de diabetes tipo 2, tras el síndrome coronario agudo. MÉTODOS: Un total de 114 pacientes fue sometido a la prueba oral de tolerancia a la glucosa (POTG), de un a tres días tras el alta hospitalaria, y luego de infarto agudo de miocardio o angina inestable. Basado en el POTG, definimos tres grupos de pacientes: tolerancia normal a la glucosa (TNG; n=26), tolerancia alterada a la glucosa (TAG; n=39) o diabetes mellitus (DM; n=49). Se utilizó el Modelo de Evaluación de la Homeostasis (HOMA-IR) para estimarse la resistencia a la insulina; se evaluó la responsividad de la célula beta a través del índice insulinogénico de 30 minutos (ΔI30/ΔG30). RESULTADOS: Basado en el HOMA-IR, los pacientes con DM se mostraban más insulinoresistentes que los individuos con TNG o TAG (p<0,001). De acuerdo con el índice insulinogénico, la responsividad de la célula beta también estaba alterada en individuos con DM (p<0,001 vs. TNG o TAG). CONCLUSIONES: Se encontraron altas tasas de alteraciones glucometabólicas tras el síndrome coronario agudo en pacientes con SM. Como esas anormalidades incrementan acentuadamente el riesgo de desenlaces adversos, el POTG precoz se puede utilizar en pacientes con SM para identificar a los que presentan mayor riesgo coronario.