Introdução: A quantificação da isquemia miocárdica é um dado de grande auxílio na tomada de decisões clínicas ou intervencionistas no tratamento da doença arterial coronária (DAC) avançada. Dentre os métodos disponíveis para esta finalidade, se destacam a cintilografia de perfusão miocárdica (CPM) e a ressonância magnética cardíaca (RMC), que além de fornecerem informações quanto à alteração de motilidade entre o estresse e o repouso, são capazes de analisar a perfusão miocárdica. Neste estudo, investigamos a correlação e a concordância entre esses dois métodos em pacientes com DAC sintomática e avançada. Métodos e Resultados: Cinquenta e três pacientes com DAC avançada (padrão obstrutivo triarterial) não elegíveis para revascularização completa devido à extensão e caráter difuso das lesões foram submetidos à RMC e à CPM. A maioria (57%) apresentava sintomas limitantes (angina CCS 3 ou 4). Na quantificação da carga isquêmica, o percentual de miocárdio isquêmico total (%Mioisquêmico) foi significativamente maior na RMC do que na CPM (25,3±13,7% vs. 20,5±13,5%, respectivamente; P = 0,02). A RMC identificou baixa carga isquêmica em apenas 15% dos pacientes, enquanto pela CPM 53% dos pacientes foram assim classificados. Foram encontradas correlações fracas entre os métodos para o %Miofixo, no %Mioestresse e %Mioisquêmico (coeficiente de Spearman variando de 0,06 a 0,54), assim como uma fraca concordância (kappa de 0,11 e bias elavado de 9,3 para %Mioisquêmico). De um total de 159 territórios coronarianos, 18 (11%) apresentaram grandes discordâncias (%Mioisquêmico pela CPM < 10% e > 20% pela RMC) em regiões do ventrículo esquerdo com alta probabilidade pré-teste de possuírem isquemia importante (miocárdio viável em território irrigado por artéria coronária ocluída cronicamente). Conclusão: A quantificação da carga isquêmica estresse-induzida avaliada pela CPM e pela RMC possui fraca correlação e concordância em pacientes com DAC avançada e complexa, com a RMC demonstrando uma maior carga isquêmica do ventrículo esquerdo, principalmente nas regiões com infarto prévio / Introduction: The quantification of myocardial ischemia is a key element in the decision-making process in patients with advanced coronary artery disease (CAD). Single-photon emission computed tomography (SPECT) and cardiovascular magnetic resonance (CMR) are non-invasive tools for myocardial perfusion assessment. We investigated the correlation and agreement between these two methods in patients with symptomatic and complex CAD. Methods and Results: Fifty-three patients with advanced CAD (multivessel obstructive disease) not eligible for complete revascularization due the extension and diffuseness of the disease underwent both CMR and SPECT. The majority (57%) presented limiting symptoms (angina CCS 3 or 4). The quantification of the ischemic burden revealed that the mean percentage of total ischemic myocardium (%Myoischemic) was significantly higher as assessed by CMR compared with by SPECT (25.3±13.7% vs. 20.5±13.5%, respectively; P = 0.02). There were no significant correlations between CMR and SPECT regarding %Myostress (r = 0.23, p = 0.09), fixed (r = 0.20, p = 0.14), or ischemic (r = 0.11, p = 0.44). While SPECT classified 28 patients (53%) as having low ischemic burden (%Myoischemic < 10%), CMR classified only 8 patients (15%) in this category. Poor correlations between the two methods were found for %Myostress, %Myoischemic, and %Myofixed (Spearman\'s rho ranging from 0.06 to 0.54), depicting also slight agreement (kappa of 0.11 and bias as high as 9.3% for %Myoischemic). On a per-segment-based analysis, 18 coronary territories (11%) of the total 159, presented highly disagreements (%Myoischemic by SPECT < 10% and > 20% by CMR) in LV regions likely to have severe ischemia (viable myocardium supplied by chronically occluded vessels. Conclusion: The quantification of inducible myocardial ischemia by SPECT and CMR disagrees in patients with advanced and complex CAD, with CMR displaying greater left ventricular ischemic burden, particularly in patients with a previous myocardial infarction

A doença cardiovascular (DCV) é a principal causa de mortalidade e morbidade em pacientes portadores de diabetes mellitus tipo 2 (DM 2), estando associada com mais de 80% das mortes nesses pacientes. Portadores de DM 2 têm um risco três vezes maior em relação à indivíduos não diabéticos de desenvolver aterosclerose e suas complicações clínicas como infarto agudo do miocárdio (IAM), acidente vascular cerebral (AVC) e doença vascular periférica. O sistema endócrino da vitamina D regula a diferenciação e a proliferação de vários tipos celulares, além de possuir propriedades antiinflamatórias e antiangiogênicas. Assim, a vitamina D poderia ter um papel protetor contra as doenças degenerativas crônicas como a DCV. Estudos epidemiológicos sugerem que a deficiência de vitamina D está associada com doença arterial coronariana (DAC). As ações da 1,25(OH)2D3 são mediadas pela sua ligação ao seu receptor nuclear (VDR). O objetivo do presente estudo foi investigar as associações de polimorfismos de um único nucleotídeo (SNPs) no gene VDR com DAC em duas coortes de pacientes portadores de DM 2. Um total de 3.137 pacientes provenientes do estudo prospectivo DIABHYCAR (14,8% de incidência de DAC no seguimento) foi estudado. Uma outra coorte (NECKER - COCHIN) independente composta de 713 indivíduos portadores de DM 2 (32,3% dos quais tinham DAC) também foi avaliada. Três SNPs no gene VDR foram genotipados: rs1544410 (BsmI), rs7975232 (ApaI) e rs731236 (TaqI). Uma associação do alelo A de BsmI com casos incidentes de DAC (Hazard Ratio = 1,16; IC 95% = 1,05-1,29; p = 0,002) foi observada, assim como associações do alelo A de BsmI (p = 0,01) e do alelo C de TaqI (p = 0,04) com casos de DAC no início do estudo. O haplótipo AAC (BsmI / ApaI / TaqI) foi significantemente associado com aumento da prevalência de DAC no final do estudo, em comparação com o haplótipo GCT (Odds Ratio = 1,12; IC 95% = 1,02-1,28; p = 0,04). Associações do alelo A de ApaI (p = 0,009) e do alelo C de TaqI (p = 0,05) com DAC foram observadas no estudo transversal da coorte Necker - Cochin. Os resultados obtidos com os haplótipos também foram replicados nessa coorte (Odds Ratio = 1,33; IC 95% = 1,03-1,73; p = 0,03). Em conclusão, o haplótipo composto pelo alelo raro de BsmI, pelo alelo frequente de ApaI e pelo alelo raro de TaqI (AAC) foi associado a um maior risco de DAC em pacientes portadores de DM 2. Este efeito foi independente dos efeitos de outros fatores de risco cardiovasculares / Cardiovascular (CVD) disease is the leading cause of mortality and morbidity in patients with type 2 diabetes being associated with up to 80% of the deaths in these patients. Diabetic patients have a 3-fold higher risk than non diabetic individuals for developing atherosclerosis and its clinical complications such as myocardial infarction, stroke, and peripheral vascular disease. The vitamin D endocrine system regulates the differentiation and replication of several cell types and has antiangiogenic and antiinflammatory properties. Thus, it could have a protective role against chronic degenerative disorders such as CVD. Epidemiological studies suggested that vitamin D deficiency is associated with coronary heart disease. Actions of vitamin D are mediated by the binding of 1,25-(OH)2D3 to a specific cytosolic/nuclear vitamin D receptor (VDR). The present study investigated associations of VDR gene variants with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects. A total of 3,137 subjects participating in the 6-year prospective DIABHYCAR study (14.8% of CAD incidence at follow-up) were evaluated. An independent, hospital-based cohort (NECKER-COCHIN) of 713 diabetic subjects, 32.3% of whom had CAD, was also studied. Three single nucleotide polymorphisms (SNPs) in the VDR gene were genotyped: rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI). In the DIABHYCAR cohort, an association of the A-allele of BsmI with incident cases of CAD was found (Hazard Risk = 1.16; 95% C.I = 1.05-1.29; p = 0.002). Associations were also observed for the A- allele of BsmI (p=0.01) and C-allele of TaqI (p = 0.04) polymorphic variants with baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with increased CAD prevalence at the end of the study as compared with the GCT haplotype (Odds Ratio = 1.12; 95% C.I. = 1.02-1.28; p = 0.04). Associations of ApaI (p = 0.009) and TaqI (p = 0.05) alleles with CAD were observed in a cross-sectional study of the NECKER-COCHIN cohort. The haplotype results were also replicated (Odds ratio = 1.33; 95% C.I. = 1.03 - 1.73; p = 0.03). In conclusion, the haplotype composed by the minor allele of BsmI, the major allele of ApaI and the minor allele of TaqI (AAC) was associated with increased risk of CAD in type 2 diabetic patients. This effect was independent from effects of other known cardiovascular risk factors

3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG CoA) reductase is a 97 kDa glycoprotein located in the endoplasmic reticulum responsible for cholesterol biosynthesis in mammalian liver and intestine. HMG CoA reductase inhibitors (statins) (e.g. simvastatin, mevastatin and parvastatin) are used clinically to treat and prevent coronary artery diseases by reducing plasma LDL-cholesterol level. Recent studies have demonstrated that statins can provide beneficial effects (pleiotropic effects) beyond its lipid-lowering activity. However, the modulatory effects of statins on ion channels activities have not been fully explored. Hence, this study is designed to demonstrate the existence of the HMG CoA reductase in various human isolate cardiovascular preparations and the modulatory effect(s) of simvastatin on both large-conductance calcium-activated (BKCa) and ATP-sensitive (IKATP) potassium channels of porcine isolated coronary vascular smooth muscle cells. / In conclusion, our results demonstrated the biochemical existence of HMG CoA reductase in various human isolated cardiovascular preparations and porcine isolated coronary artery. Simvastatin modulates the BKCa and IKATP channels of the porcine isolated coronary artery via different and multiple cellular mechanisms. / In this study, we demonstrated the biochemical existence of the HMG CoA reductase in various human isolated cardiovascular preparations and porcine isolated coronary artery. In addition, we demonstrated that simvastatin modulates both the BKCa channels and IKATP channels of porcine isolated coronary artery via different mechanisms. Acute application of simvastatin (100 nM) slightly enhanced whereas simvastatin (&ge; 1 muM) inhibited the BKCa amplitude of porcine coronary artery smooth muscle cells. The classical HMG CoA reductase-mevalonate cascade is important in mediating the inhibitory effect of simvastatin observed at low concentrations (1 and 3 muM), whereas an increased PKC-delta protein expression and activation is important in simvastatin (10 muM)-mediated inhibition of BKCa channels. In contrast, the basal activity of the IKATP channels was not affected by simvastatin (1, 3 and 10 muM). However, acute application of simvastatin (1, 3 and 10 muM) inhibited the opening of the IKATP channels by cromakalim and pinacidil in a PP2A-dependent manner (sensitive to okadaic acid, a PP2A inhibitor). The okadaic acid-sensitive, simvastatin-mediated inhibitory effect on IKATP channel is mediated by an activation of AMPK in a Ca2+-dependent manner. Activation of AMPK probably increased the activity of the Na+/K+ ATPase and subsequently caused an influx of glucose via the SGLT1 down the Na + concentration gradient for the ouabain-sensitive, glucose-dependent activation of PP2A. / Seto, Sai Wang. / Adviser: Yiu-Wa Kwan. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3456. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 221-254). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Introdução: A apneia obstrutiva do sono (AOS) é caracterizada por episódios recorrentes de colapso parcial ou completo da faringe responsáveis por roncos e eventos de hipopneia ou apneia, respectivamente, associados à queda de saturação de oxigênio e despertares frequentes durante o sono. A AOS está associada à doença arterial coronariana e é um fator de risco independente para complicações após cirurgia. Entretanto, a maioria dos pacientes com AOS submetidos à cirurgia não tem suspeita ou diagnóstico prévio de AOS. Objetivos: O principal objetivo do estudo foi determinar prevalência da AOS em candidatos à cirurgia de revascularização do miocárdio (RM) e compará-la à prevalência da AOS em candidatos à cirurgia abdominal eletiva (ABD-cirurgia). Como objetivo secundário, avaliamos os preditores clínicos e o desempenho do questionário de Berlin, que estratifica os pacientes em alto risco e baixo risco de AOS, como teste de triagem no pré-operatório, assim como os preditores clínicos de AOS em ambos os grupos. Métodos: Foram incluídos 40 pacientes consecutivos no grupo RM [29 homens; idade: 56±7 anos; índice de massa corporal (IMC): 30±4 kg/m2], e 41 pacientes no grupo ABD-cirurgia, que foram pareados para sexo, idade e IMC (28 homens; idade: 56±8 anos; IMC: 29±5 11 kg/m2). Todos os pacientes foram submetidos à polissonografia completa noturna (PSG) e à avaliação clínica e laboratorial pré-operatória, incluindo avaliação da sonolência diurna com a escala de sonolência Epworth (ESS) e com o questionário de Berlin. Resultados: A prevalência de AOS (índice de apneia hipopneia na PSG 15 eventos/hora) no grupo RM e ABD-cirurgia foi alta e semelhante (52% e 41%, respectivamente, p=0,32). O grupo RM apresentou menor nível de sonolência (ESS: 6±3 e 9±5; RM vs. ABD-cirurgia, respectivamente, p=0,008). A sensibilidade e a especificidade do Berlin no grupo RM foi 67% e 26%, e no grupo ABD-cirurgia, 82 e 62%, respectivamente. O IMC, as circunferências abdominal e cervical, a pressão arterial sistólica, a pressão arterial diastólica, os triglicerídeos, a lipoproteína de alta densidade sérica (HDL-c), a Diabetes Mellitus e o risco alto de AOS (de acordo com questionário de Berlin) se correlacionaram com a AOS na análise univariada. No entanto, a circunferência abdominal foi o único preditor independente associado à presença de AOS após regressão logística múltipla. Conclusão: A AOS é extremamente comum entre pacientes candidatos à cirurgia cardíaca e cirurgia abdominal. O questionário de Berlin apresentou baixa sensibilidade para detecção AOS em pacientes do grupo RM, mas a sensibilidade e a especificidade no grupo ABD-cirurgia foram semelhantes aos valores encontrados na literatura. A sonolência diurna não está associada à presença de AOS entre portadores de doença arterial coronariana com indicação de tratamento cirúrgico e entre candidatos à cirurgia abdominal eletiva, o que pode ajudar a explicar o subdiagnóstico de AOS na nossa população / Background: The obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete collapse of the pharynx account for snoring and apnea or hypopnea events, respectively, associated with the decrease of oxygen saturation and frequent arousals during sleep. OSA is associated with coronary artery disease and is an independent risk factor for complications after surgery. However, most patients with OSA undergoing surgery is not suspected or previously diagnosed OSA. Objectives: The main objective of this study was to determine the prevalence of OSA in candidates for coronary arterial bypass grafting surgery (CABG) and compare it with the prevalence of OSA in candidates for elective abdominal surgery (ABD-surgery). As a secondary objective, we evaluated the clinical predictors and performance of the Berlin questionnaire, which stratifies patients into high risk and low risk for OSA, as a screening test in the preoperative as well as clinical predictors of OSA in both groups. Methods: We included 40 consecutive patients in the CABG group [29 men, age: 56 ± 7 years, body mass index (BMI): 30 ± 4 kg/m2] and 41 patients in the ABD-surgery, who were matched for gender, age and BMI (28 men, age: 56 ± 8 years, BMI: 29 ± 5 kg/m2 ¬). All patients underwent full nocturnal polysomnography (PSG) and clinical and laboratory pre-operative evaluation, 14 including assessment of daytime sleepiness with the Epworth Sleepiness Scale (ESS) and the Berlin questionnaire. Results: The prevalence of OSA (apnea hypopnea index in PSG 15 events/hour) in the RM group and ABD-surgery was high and similar (52% and 41% respectively, p = 0.32). Patients submitted to CABG presented lower levels of daytime somnolence than ABD-surgery patients (ESS: 6±3 vs. 9±5; p=0.008, respectively). The sensitivity and specificity of Berlin in the RM group was 67% and 26%, and ABD-surgery group, 82 and 62% respectively. The BMI, waist and neck circumference, systolic blood pressure, diastolic blood pressure, triglycerides, serum high density lipoprotein (HDL-C), Diabetes Mellitus and the high risk of OSA (according to questionnaire Berlin) correlated with OSA in univariate analysis. However, waist circumference was the only independent predictor associated with the presence of OSA after multiple logistic regression. Conclusion: OSA is extremely common among patients who are candidates for CABG and abdominal surgery. The Berlin questionnaire showed low sensitivity for detecting OSA in patients in the RM group, but the sensitivity and specificity in ABD-surgery group were similar to those found in the literature. Daytime sleepiness is not associated with the presence of OSA among patients with coronary artery disease with indication for surgical treatment and patients with indication for elective abdominal surgery, which may help explain the underdiagnosis of OSA in our population

Objetivo: A doença cardiovascular é umas das principais causas de mortalidade tardia não relacionada ao fígado após o transplante hepático. O objetivo deste estudo foi avaliar os efeitos a longo prazo do transplante hepático sobre o perfil metabólico e o sistema cardiovascular. Métodos: Trinta e seis receptores de fígado foram avaliados um ano após o transplante hepático para avaliar a prevalência da síndrome metabólica e outros preditores de doenças cardiovasculares. Foram coletados dados antropométricos, exames bioquímicos, biomarcadores de aterosclerose e calculado o escore de Framingham. Quatro anos após o transplante, essa avaliação foi repetida e todos os participantes foram submetidos a uma tomografia de coronárias para obtenção do escore de cálcio coronariano. Os dados obtidos foram comparados para estimar a progressão do risco cardiovascular. Resultados: A população era constituída na sua maioria por indivíduos do sexo masculino, de cor branca e transplantados por hepatite C. Observou-se um aumento estatisticamente significativo na circunferência abdominal e na prevalência de dislipidemia, obesidade e síndrome metabólica ao longo do tempo. Todos os biomarcadores de aterosclerose estudados apresentaram aumento importante dos seus níveis no quarto ano (p < 0,001) após o transplante. Quanto ao escore de cálcio, 25% dos pacientes apresentaram calcificação coronariana moderada a grave, conferindo maior risco de evento cardíaco. A mediana do escore de Framingham aumentou substancialmente do primeiro ao quarto ano (p=0,022), alterando a estratificação de baixo para alto risco. Isso se refletiu em um aumento significativo de eventos cardiovasculares após quatro anos de transplante hepático. Conclusões: A prevalência de síndrome metabólica e risco cardiovascular aumenta significativamente do primeiro ao quarto ano após transplante hepático. O escore de cálcio coronariano e os biomarcadores de aterosclerose podem melhorar a estratificação de risco e ajudar a prevenir a progressão de doenças cardiovasculares / Objective: Cardiovascular diseases are a major non-liver-related contributor to late mortality after liver transplantation. The aim of this study was to assess the long-term effects of liver transplantation on the metabolism and cardiovascular system. Methods: Thirty-six liver recipients were assessed one year after transplantation to evaluate the prevalence of metabolic syndrome and other predictors of cardiovascular diseases. The data collected included anthropometric features, biochemical test results, Framingham risk score and atherosclerosis biomarkers. This evaluation was repeated four years after transplantation, and a coronary artery calcium score was obtained from all participants. Data were compared to estimate cardiovascular risk progression. Results: The population consisted mostly of white male subjects who underwent transplantation for hepatitis C. Significant increases were observed in waist circumference and the prevalence of dyslipidemia, obesity and metabolic syndrome over time. All biomarkers of atherosclerosis studied showed increased levels at the fourth year (p < 0.001). Regarding the calcium score, 25% of patients had moderate to severe coronary artery calcification, conferring an enhanced risk of a cardiac event. The median Framingham risk score substantially increased from the first to fourth year (p=0.022), changing the stratification from low to high risk. This change was reflected in a significant increment of cardiovascular events four years after liver transplantation. Conclusions: The prevalence of metabolic syndrome and cardiovascular risk significantly increased from the first to fourth year after liver transplantation. Coronary artery calcium scores and atherosclerosis biomarkers may improve risk stratification and help prevent symptomatic cardiovascular disease

Introdução: O diagnóstico infarto do miocárdio (IAM) Tipo 5 é bastante complexo, especialmente após o surgimento de ensaios com a troponina de alta sensibilidade. Objetivo: Mensurar a liberação de biomarcadores de necrose miocárdica após cirurgia de revascularização (RM) utilizando a circulação extracorpórea (CEC) na ausência de novo realce tardio pelo gadolínio (RTG). Métodos: Neste estudo, avaliamos pacientes com doença arterial coronária estável, multiarterial, função do ventrículo esquerdo preservada, biomarcadores cardíacos basais normais e indicação formal para a cirurgia de revascularização eletiva com CEC. Eletrocardiograma, coleta de amostras de sangue para a mensuração de troponina e CKMB, e ressonância magnética cardíaca (RMC) com realce tardio pelo gadolíneo (RTG) foram efetuadas antes e após o procedimento. O diagnóstico de IM foi definido como acima de 10 vezes o percentil 99 URL, para troponina e CK-MB, respectivamente, e novo RTG pela RMC. Resultados: De 75 pacientes selecionados para RM com CEC, 69 foram analisados; destes, 54 não apresentaram RTG (IAM tipo 5 na RMC). 39 pacientes eram do sexo masculino (72,2%), com idade média de 61,3 (±8,3) anos. A pontuação média do SYNTAX Score foi de 28 (±10). Após a cirurgia, 54 (100%) pacientes tiveram um pico de troponina acima do percentil 99; destes, em 52 (96%) este pico foi maior do que 10 vezes o percentil 99. Por outro lado, 54 (100%) pacientes alcançaram pico de CK-MB acima do limite do percentil 99 e em apenas 13 (24%) foi maior do que 10 vezes o percentil 99. A troponina apresentou mediana do pico de 3,15 (2,0 - 4,9) ng/mL, 78,75x superior ao percentil 99. Conclusão: Nesta amostra estudada, a CKMB, diferentemente da troponina, teve níveis de liberação dentro dos padrões recomendados pelas diretrizes e coincidiu com ausência de realce na RMC. Estes dados permitem sugerir um maior ponto de corte de troponina para o diagnóstico do IAM relacionado ao procedimento / Background: The diagnosis of periprocedural myocardial infarction is complex, especially after the emergence of high-sensitive markers of myocardial necrosis. Methods: In this prospective study, patients with stable multivessel coronary disease, preserved left ventricular function, normal baseline cardiac biomarkers, and formal indication for elective on-pump coronary bypass surgery (ONCAB) were evaluated. Electrocardiograms, cardiac biomarkers CKMB and troponin I (cTnI), and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement were performed before and after procedures. Myocardial infarction (MI) was defined as more than ten times the upper reference limit of the 99th percentile for cTnI and for CKMB and by the findings of new late gadolinium enhancement on CMR. We assessed the release of cardiac biomarkers in patients with no evidence of myocardial infarction on CMR. Results: From 75 patients referred to ONCAB, 69 were analyzed in this study. From these, 54 patients did not have evidence of MI on CMR. This group had 39 men (72.2%), mean age of 61.3 (± 8.3) years and a mean SYNTAX Score of 28 (± 10). After CABG, all 54 (100%) patients had a peak cTnI above the 99th percentile, and 52 (96%) had an elevation 10 times higher than the 99th percentile. Regarding CKMB, 54 (100%) patients had a peak CKMB above the 99th percentile limit, and only 13 (24%) had an elevation greater than 10 times the 99th percentile. The median value of cTnI peak was 3.15 (2.0 to 4.9) ng/mL. This represented 78.75 times the 99th percentile. Conclusion: In this sample, CKMB, unlike cTnI, had levels of release within the standards recommended by the guidelines and coincided with lack of enhancement in CMR. These data suggest a higher troponin cutoff point for the diagnosis of MI related to the procedure

A doença arterial coronariana (DAC) pode alterar o balanço simpato-vagal do Sistema Nervoso Autônomo (SNA) e aumentar os riscos de arritmias fatais e morte súbita. O exercício físico pode reverter essa condição, porém poucos estudos analisam o ajuste hemodinâmico ao exercício dinâmico resistido, especialmente em portadores de DAC. Além disso, exercícios de membros superiores podem induzir diferentes repostas comparado aos de membros inferiores, porém os estudos comparando os dois tipos de exercícios são escassos. O objetivo do estudo foi analisar as respostas cardiovasculares no exercício resistido de membros superiores e compará-las com o exercício resistido de membros inferiores, em idosos saudáveis e em portadores de DAC. Para a realização do estudo, foram selecionados 20 indivíduos do sexo masculino, sendo 10 idosos saudáveis e 10 idosos portadores de DAC, não etilistas, não tabagistas, e sem distúrbios respiratórios, neurológicos, metabólicos e articulares. Foram realizados: teste de 1RM em exercício resistido no supino inclinado e no leg-press 45°; teste de esforço físico dinâmico resistido com diferentes percentuais de 1RM, com carga inicial de 10% da 1RM e increntos de 10% da 1RM, e a partir de 30% os incrementos passaram a ser de 5% da 1RM. No supino inclinado, houve diminuição significativa do índice rMSSD a partir de 30% da 1RM (GC: de 20±2 ms para 11 ±3 ms; GDAC: de 19±3 ms para 9±1 ms) em ambos os grupos, semelhantemente ao índice SD1 (GC: de 14±2 ms para 8±1; GDAC: 14±2 ms para 7±1 ms). O índice RMSM se manteve sem diferenças entre as cargas no grupo controle (GC) (de 28±3 ms para 45±9 ms), porém aumentou significativamente no grupo DAC (GDAC)(22±2 ms para 79±33 ms). A FC aumentou significativamente a partir de 30% da 1RM em ambos os grupos (GC: de 69±3 bpm para 93±6 bpm; GDAC: 59±3 bpm para 75±4 bpm). No leg-press 45º, houve diminuição do índice rMSSD a partir de 30% da 1RM em ambos os grupos (GC: 29±5 ms para 12±2 ms; GDAC: 28±4 ms para 18±3 ms). O índice SD1 diminuiu no GC a partir de 30% da 1RM (de 23±4 mas para 7±1) e no GDAC a partir de 20% da 1RM (de 16±3 para 11±1). O índice RMSM diminuiu a partir de 30% da 1RM no GC (34±5 ms para 14±3 ms) e aumentou a partir de 35% da 1RM no GDAC (28±4 ms para 43±5 ms). A FC aumentou a partir de 30% da 1RM no GC (65±3 bpm para 92±4 bpm) e a partir de 35% da 1RM no GDAC (61±1 para 76±3). Comparando as variáveis entre os equipamentos, observaram-se menores valores do índice SD1 no GDAC a partir de 35% da 1RM no supino. Também se observaram maiores valores do índice RMSM no GDAC a partir de 30% da 1RM no supino inclinado. Como conclusão, pode-se inferir que houve diminuição parassimpática e aumento da modulação simpática a partir de 30% da 1RM em ambos os equipamentos, sendo que o supino inclinado produziu marcada atenuação parassimpática associada a maior modulação simpática. / Coronary artery disease (CAD) can alter the balance of the sympatho-vagal autonomic nervous system (ANS) and increase the risk of fatal arrhythmias and sudden death. Exercise can reverse this condition, but few studies analyze the hemodynamic adjustment to dynamic resistance exercise, especially in patients with CAD. In addition, upper exercise may induce different responses compared with the lower limbs, but studies comparing the two conditions of resistance exercise are scarce. The objective of the study was to assess the cardiovascular responses in resistance of the upper and compare them with the lower limb resistance exercise in healthy elderly and in patients with CAD. We selected 20 males, 10 healthy elderly and 10 elderly patients with CHD, non-alcohol drinkers, non-smokers, and without respiratory, neurological and metabolic diseases. Were performed: 1RM test in the bench press inclined and leg-press 45 °, and an incremental dynamic resistance test different percentages of 1RM, with initial load of 10% of 1RM and increments of 10% of 1RM, and from 30 % increments was 5% of 1RM. On the bench press inclined, there was significant decrease in RMSSD index from 30% of 1RM (CG: 20 ± 2 ms to 11 ± 3 ms; GDAC: 19 ± 9 ms to 3 ± 1 ms) in both groups, similarly SD1 index (CG: 14 ± 2 to 8 ± 1 ms; GDAC: 14 ± 2 ms to 7 ± 1 ms). The RMSM index remained no differences between the loads in the control group (CG) (28 ± 3 ms to 45 ± 9 ms), but increased significantly in the CAD group (GDAC) (22 ± 2 ms to 79 ± 33 ms). The HR increased significantly from 30% of 1RM in both groups (CG: 69 ± 3 bpm to 93 ± 6 bpm; GDAC: 59 ± 3 bpm to 75 ± 4 bpm). In the leg-press 45º, the RMSSD index decreased from 30% of 1RM in both groups (CG: 29 ± 5 ms to 12 ± 2 ms; GDAC: 28 ± 4 ms to 18 ± 3 ms). The SD1 index decreased in GC from 30% of 1RM (23 ± 4 ms to 7 ± 1 ms) and GDAC from 20% of 1RM (16 ± 3 ms to 11 ± 1 ms). The RMSM index decreased from 30% of 1RM in the GC (34 ± 5 ms to 14 ± 3 ms) and increased from 35% of 1RM in the GDAC (28 ± 4 ms to 43 ± 5 ms). The HR increased from 30% of 1RM in the GC (65 ± 3 bpm to 92 ± 4 bpm) and from 35% of 1RM in the GDAC (61 ± 1 to 76 ± 3). Comparing the variables between the equipment, there were lower values for SD1 from GDAC in 35% of 1RM on the bench press. Also observed higher values in the index RMSM in GDAC from 30% of the 1RM bench press inclined. It can be inferred that decreased parasympathetic and increased in sympathetic modulation from 30% of 1RM in both equipments, and the bench press inclined produced marked attenuation in parasympathetic modulation with an increased in sympathetic modulation.

<p>Tissue factor (TF) is the initiator of the coagulation cascade. Monocytes do not normally express TF, but can be induced to do so by certain stimuli. Aberrant TF expression is important in the thrombotic complications of bacterial sepsis, certain malignancies and coronary artery disease (CAD). In this thesis, regulation of monocyte TF by cytokines and by interactions with other vascular cells were studied, as well as the activation of blood cells, inflammation and coagulation in CAD patients and the association of the pro-inflammatory cytokine interleukin (IL)-6 with prognosis in unstable CAD. </p><p>In a whole blood experimental system, the anti-inflammatory cytokine IL-10 was shown to suppress lipopolysaccharide-induced TF expression in monocytes, whereas IL-4 and IL-13 did not, contrary to previous in vitro findings. Activated platelets also induced monocyte TF in whole blood in a P-selectin-dependent manner, causing a rapid surface exposure of TF independent of mRNA formation. The differentiated monocytic cell line U-937 displayed different kinetics of platelet-stimulated TF induction.</p><p>In co-culture with cytokine-activated human coronary artery endothelial cells, U-937 cells expressed TF, and also IL-6. The endothelial cells up-regulated their production of IL-10. Simvastatin, enalapril and dalteparin, all commonly used drugs in CAD treatment, suppressed TF induction but did not alter cytokine expression in co-cultures.</p><p>In unstable CAD, there was an activation of both coagulation and inflammation compared to stable CAD that coincided with an increased activation of platelets and leukocytes. Women had different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms.</p><p>Plasma levels of IL-6 above 5 ng/L proved to be a strong, independent marker for increased risk of death in a 6-12 month perspective in patients with unstable CAD. This risk was significantly reduced by an early invasive strategy.</p>

Tissue factor (TF) is the initiator of the coagulation cascade. Monocytes do not normally express TF, but can be induced to do so by certain stimuli. Aberrant TF expression is important in the thrombotic complications of bacterial sepsis, certain malignancies and coronary artery disease (CAD). In this thesis, regulation of monocyte TF by cytokines and by interactions with other vascular cells were studied, as well as the activation of blood cells, inflammation and coagulation in CAD patients and the association of the pro-inflammatory cytokine interleukin (IL)-6 with prognosis in unstable CAD. In a whole blood experimental system, the anti-inflammatory cytokine IL-10 was shown to suppress lipopolysaccharide-induced TF expression in monocytes, whereas IL-4 and IL-13 did not, contrary to previous in vitro findings. Activated platelets also induced monocyte TF in whole blood in a P-selectin-dependent manner, causing a rapid surface exposure of TF independent of mRNA formation. The differentiated monocytic cell line U-937 displayed different kinetics of platelet-stimulated TF induction. In co-culture with cytokine-activated human coronary artery endothelial cells, U-937 cells expressed TF, and also IL-6. The endothelial cells up-regulated their production of IL-10. Simvastatin, enalapril and dalteparin, all commonly used drugs in CAD treatment, suppressed TF induction but did not alter cytokine expression in co-cultures. In unstable CAD, there was an activation of both coagulation and inflammation compared to stable CAD that coincided with an increased activation of platelets and leukocytes. Women had different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms. Plasma levels of IL-6 above 5 ng/L proved to be a strong, independent marker for increased risk of death in a 6-12 month perspective in patients with unstable CAD. This risk was significantly reduced by an early invasive strategy.

The initial treatment options for patients with stable coronary artery disease include optimal medical therapy alone, or coronary revascularization with optimal medical therapy. The most common revascularization modality is percutaneous coronary intervention (PCI) with either bare metal stents (BMS) or drug-eluting stents (DES). PCI is believed to reduce recurrent angina and thereby decrease the need for additional procedures compared to optimal medical therapy alone. It remains unclear if these benefits are sufficient to offset the increased costs and small increase in adverse events associated with PCI. The objectives of this thesis were to determine the degree of angina relief afforded by PCI and develop a tool to provide contemporary estimates of the impact of angina on quality of life. In addition, we sought to develop a comprehensive state-transition model, calibrated to real world costs and outcomes to compare the cost-effectiveness of initial medical therapy versus PCI with either BMS or DES in patients with stable coronary artery disease. ii We performed a systematic search and meta-analysis of the published literature. Although PCI was associated with an overall benefit on angina relief (odds ratio [OR] 1.69; 95% Confidence Interval [CI] 1.24-2.30), this benefit was largely attenuated in contemporary studies (OR 1.13; 95% CI 0.76-1.68). Our meta-regression analysis suggests that this observation was related to greater use of evidence-based medications in more recent trials. Using simple linear regression, we were able to create a mapping tool that could accurately estimate utility weights from data on the Seattle Angina Question, the most common descriptive quality of life instrument used in the cardiovascular literature. In our economic evaluation, we found that an initial strategy of PCI with a BMS was cost- effective compared to medical therapy, with an incremental cost-effectiveness ratio (ICER) of $13,271 per quality adjusted life year gained. In contrast, DES had a greater cost and lower survival than BMS and was therefore a dominated strategy.