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.

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.

No description available.

Les biomarqueurs plasmatiques constituent des outils essentiels, mais rares, utilisés pour diagnostiquer les maladies, comme les maladies cardiovasculaires (MCV), et stratifier le niveau de risque associé. L’identification de nouveaux biomarqueurs plasmatiques susceptibles d’améliorer le dépistage et le suivi des MCV représente ainsi un enjeu majeur en termes d’économie et de santé publique. Le projet vise à identifier de nouveaux biomarqueurs plasmatiques prédictifs ou diagnostiques des MCV, à déterminer le profil protéomique plasmatique de patients atteints de MCV et à développer des méthodes innovantes d’analyse d’échantillon plasmatique. L’étude a été effectuée sur une large banque de plasma provenant de 1006 individus de souche Canadienne-Française recrutés à différents stades de la MCV et qui ont été suivis sur une période de 5 ans. Des séries de déplétions ont été réalisées afin de dépléter les 14 protéines majoritaires (colonne IgY14TM) de l’échantillon avant son analyse par trois approches effectuées en parallèle: 1) Une chromatographie liquide (LC) en 2 dimensions qui fractionne les protéines selon le point isoélectrique puis selon le degré d’hydrophobicité, via le système PF2D, suivie par une chromatographie liquide couplée avec une spectrométrie de masse en tandem (LC-MS/MS). 2) Une séparation classique sur gel 1D-SDS-PAGE suivie d’une LC-MS/MS; 3) Par une déplétion plus poussée du plasma avec l’utilisation en tandem avec la colonne IgY14TM d’une colonne SupermixTM permettant de dépléter également les protéines de moyenne abondance, suivie d’une séparation sur gel 1D-SDS-PAGE et d’une analyse LC-MS/MS de la portion déplétée (3a) et de la portion liée à la SupermixTM (3b). Les résultats montrent que le système PF2D permet d’identifier plusieurs profils protéiques spécifiques au groupe MCV. Sur un total de 1156 fractions (équivalent à 1172 pics protéiques pour le groupe contrôle et 926 pics pour le groupe MCV) recueillies, 15 fractions (23 pics protéiques) présentaient des différences quantitativement significatives (p<0,05) entre les 2 groupes. De plus, 6 fractions (9 pics) sont uniquement présentes dans un groupe, représentant d’autres signatures protéomiques et biomarqueurs potentiellement intéressants. Les méthodes 2, 3a et 3b ont permis l’identification de 108, 125 et 91 protéines respectivement avec des chevauchements partiels (31% entre la méthode 2 et 3a, 61% entre 2 et 3b et 19% entre 3a et 3b). Les méthodes 2 et 3 ont permis l’identification de 12 protéines qui présentaient des différences quantitatives significatives entre les 2 groupes. L’utilisation de plusieurs approches protéomiques complémentaires nous ont d’ores et déjà permis d’identifier des candidats biomarqueurs des angines instables avec récidive d’infarctus du myocarde (IM). / Coronary artery disease (CAD) is a major cause of mortality in Canada. Biomarkers are precious tools to diagnosis and risk stratification, and the identification of new candidates may substantially impact on public health and health economics. Due to its complexity, the human blood proteome remains challenging to explore. Our study aims at combining various complementary methods to determine the plasma proteome signature of patients at various stages of CAD. The total cohort includes 1006 French-Canadian, 500 controls with a normal coronary angiography, and 506 patients with documented CAD. Two pools were reconstituted to represent the extremes of our population: 1) patients with a previous myocardial infarction (MI) and a recurrent MI over a 5 years follow-up and 2) controls without CAD and no events during follow-up matched for age and sex to the CAD pool (N=18). After a depletion of highly abundant proteins, pools were analyzed using 3 different proteomic methods: i) PF2D system followed by a liquid chromatography tandem mass spectrometry analysis (LC-MS/MS); ii) 1D-SDS-PAGE followed by LC-MS/MS; iii) Further depletion of proteins followed by 1D-SDS-PAGE and LC-MS/MS analysis of both flow through (3a) and retained fractions (3b). Methods 2, 3a, and 3b allowed identification of 108, 125 and 91 proteins respectively. Overlapping proteins (31% between methods 2 and 3a, 61% between 2 and 3b and 19% between 3a and 3b) showed significant absolute and relative expressions with various methods. A total of 12 proteins were significantly (p<0.05) different in amounts (number of peptides identified) between the 2 pools. Analyses with the PF2D elution spectra (method 1) displayed numerous different profiles between the two groups. Over a total of 1156 fractions (control: 1172 peaks ACS: 926 peaks) generated, 370 fractions (674 peaks) overlapped between the two pools. 15 fractions (23 peaks) differed significantly (p<0,05) in amounts while some other peaks were uniquely present in one pool, representing biomarkers of potential interest. We conclude that plasma proteome signatures are significantly modeled by the methods serving their recognition. Cost of analyses can be reduced with the PF2D method by performing a pre-selection before MS analysis. Detection of less abundant proteins can be improved by using further depletion. Taking profit of these finding, we are now testing in our population the hypothesis that a combination of methods will sharpen our ability to detect clinically relevant proteins tailored to various clinical situations and to disease staging.

The objectives of this thesis are: a) To examine racial/ethnic differences in coronary artery calcification (CAC) and CAD, between symptomatic South Asians and Caucasians, matched for age, gender and conventional cardiovascular risk factors, b) To assess, using a meta-analysis model, the natural history of and stability of measurements of coronary artery calcium scoring (CACs) based on data collected from two large published trials: St Francis and EBEAT, c) To investigate the prevalence of coronary artery calcification in individuals with CT evidence for AVC, mitral valve calcification (MAC) or of both of them (AVC+MAC), d) To assess any potential association between premature CAD (&lt;55 years in first-degree male relatives and &lt;65 years in first-degree female relatives) and CAC in a large cohort of asymptomatic individuals. We found that coronary artery calcification is more extensive and diffuse in symptomatic patients of South Asian ethnic origin as compared to Caucasians, despite similar conventional risk factors for CAD. This is more evident in those &gt;50 years of age, suggesting potential genetic or other risk factors yet to be determined. The natural history of coronary artery calcification was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA brances are influenced by the branch allocation of the CACs. Valve calcification is not isolated but involve also and the coronary arteries. The presence of calcification in the aortic valve or combined aortic and mitral valves predicted coronary artery calcification. Additionally patients in whom both valves have become calcified tend to have severe coronary artery calcification. And finally, there is no relationship between the prevalence and extent of coronary artery calcification and the presence of family history of coronary heart disease in asymptomatic individuals with none of the conventional risk factors for atherosclerosis.

Research indicates that law enforcement officers (LEOs) have a higher prevalence of developing coronary artery disease (CAD) compared to the general population. Sleep deprivation and physical inactivity have been found to be related to many risk factors for CAD. This cross-sectional study examined the health status and the relationship between sleep and physical activity outcomes versus CAD risk factors among 27 University LEOs. The subjects’ health behaviors, and CAD and metabolic syndrome risk factors were described using basic statistics. Accelerometer derived sleep and physical activity outcomes were correlated to measures of health to identify potential relationships. 33% of LEOs were classified as moderate risk for CAD; 92% had dyslipidemia, 58% had elevated triglycerides, 23% had prediabetes, and 22% suffered from obesity. The administrators and first shift LEOs slept more compared to second or third shift LEOs. The LEOs were more sedentary while on-duty. In addition, sedentary time was correlated to systolic blood pressure. LEOs accumulated 24.4 min·d-1 of moderate-to-vigorous physical activity (MVPA), but only spent 9.3 min·d-1 in continuous bouts of MVPA. In conclusion, multiple CAD risk factors were present in these LEOs and achieving adequate amounts of physical activity and sleep may decrease their risk of developing chronic diseases.