D.Litt. et Phil. (Psychology) / It is an accepted fact that the incidence of coronary heart disease has reached endemic proportions in South Africa. One of the fastest growing clinical populations in this domain is that of the coronary artery bypass patient. As a result the facilities catering to the biomedical needs of this population are amongst the most sophisticated in the world. However, facilities for the effective psychosocial rehabilitation of these patients are relatively scarce. When they are addressed they tend to focus essentially on secondary emotional factors impeding reintegration back into society. A sadly neglected psychosocial factor and independent risk factor is that of the Type A behaviour pattern. Extensive research in this area has not only found this behaviour pattern to be detrimental to effective rehabilitation but has also found it to be instrumental in the reocclusion of grafted blood vessels resulting in an elevated re-operation rate as well as putting these patients at risk for a potentially fatal coronary event. In an attempt to address this problem a rehabilitation group intervention program adapted for South African conditions was launched. This program was based on the Recurrent Coronary Prone Prevention Project intended for the treatment of post-myocardial infarct patients in San Francisco. Essentially the aim of the project was to ascertain whether this intervention could be applied effectively to the coronary artery bypass population and whether its duration could significantly shortened so as to be more economically viable given the limited economic resources characteristic of the health care services in this country. The modified programme was administered to a group of 13 post-coronary artery bypass graft patients at two local cardiac rehabilitation centres. A second group of 10 patients at these same centres served as a no-treatment waiting list control group, while simultaneously undergoing an aerobic exercise and cardiovascular counselling programme. Results of the study indicate the modified programme to be highly successful in modifying Type A behaviour and its components within the South African context in the post coronary artery bypass patient samples exposed to it. Comparisons of the experimental and control groups after the intervention showed statistically significant differences on the majority of measures. Thus it was- concluded that the modified programme has the potential to be an invaluable aid in the treatment of .this population in South Africa. Presently, however, this sample is being monitored longitudinally in order to ensure that the treatment benefits remain.

The potential that telemedicine interventions may have in effectively delivering remote specialized cardiovascular care to large numbers of patients with heart diseases has recently come under question. In the first phase of this thesis, a systematic review and meta-analysis was conducted to compare the impact of a basic form of telemedicine that is regular patient follow-up by telephone, with usual care for individuals with coronary artery disease following their discharge. In the second phase of this thesis, a network meta-analysis, using Bayesian methods for multiple treatment comparisons, was conducted to compare the more complex forms of telemedicine for patients with heart failure. In the third and final phase of this thesis, a randomized controlled trial was designed to compare the impact of two forms of telemedicine, identified in the earlier two phases as being the most promising, on clinical outcomes, cardiac risk factors and patient reported outcomes.

Une augmentation de l’activité de la protéine de transfert des esters de cholestérol (CETP) est retrouvée associée à une élévation du développement de l’athérosclérose. L’apolipoprotéine C1 est l’inhibiteur physiologique de la CETP. Ses propriétés électrostatiques jouent un rôle important dans sa capacité d’inhibition de l’activité CETP. Aucune étude de ce potentiel inhibiteur de l’apoC1 n’a été réalisée chez des patients à haut risque cardio-vasculaire ou dyslipidémiques. Nous avons souhaité étudier la fonctionnalité de l’apoC1 par rapport à la CETP chez des patients coronariens normolipidémiques et hyperlipidémiques d’une part et chez des patients diabétiques de type 1 et de type 2 en comparaison à des sujets sains normolipidémiques d’autre part. Nous avons confirmé que l’apoC1 était un inhibiteur physiologique de la CETP chez l’homme normolipidémique. Nous avons montré pour la première fois la perte de cette capacité d’inhibition en cas d’hyperlipidémie chez des sujets coronariens et en cas de diabète de type 1 ou de type 2.En cas d’hyperlipidémie, l’hypertriglycéridémie joue un rôle important en stimulant la réaction de transfert des esters de cholestérol. La possible modification de répartition de l’apoC1 entre HDL et VLDL secondaire à l’hyperlipidémie est probablement également impliquée dans cette perte de fonctionnalité. Au cours du diabète, notamment de type 1, nous avons démontré que l’hyperglycémie, à l’origine du phénomène de glycation, participe, au moins en partie, à cette perte de potentiel inhibiteur. Nous avons également mis en évidence que la glycation in vitro de l’apoC1 modifiait sa charge électrostatique, facteur déterminant de son potentiel inhibiteur. / High cholesteryl ester transfer protein (CETP) activity was found to accelerate the progression of atherosclerosis. Apolipoprotein C1 (apoC1) is a potent physiological inhibitor of CETP. ApoC1 operates as CETP inhibitor through its ability to modify the electrostatic charge at the lipoprotein surface. The inhibitory potential of apoC1 has never been studied in high risk patients or in patients with hyperlipidemia. Our aim was to address the functionality of apoC1 as CETP inhibitor in normo- and hyperlipidemic patients with documented coronary artery disease and in patients with type 1 and type 2 diabetes in comparison with normolipidemic-normoglycemic healthy subjects. We confirmed that apoC1 is a physiological inhibitor of CETP in normolipidemic subjects. We showed for the first time that this inhibitory potential is lost in hyperlipidemic patients with coronary artery disease and in patients with type 1 or type 2 diabetes. During hyperlipidemia, abundant triglyceride-rich lipoproteins, as preferential acceptors of HDL cholesteryl ester, probably drive the CETP-mediated cholesteryl ester transfer reaction. The modified distribution of apoC1 between HDL and VLDL might play a role in this loss of inhibitory property. During diabetes, especially in type 1, we showed that hyperglycemia, responsible for glycation, is involved, at least in part, in this loss of CETP inhibitory ability of apoC1. We also showed that in vitro glycation of apoC1 changed its electrostatic properties, which is recognized as a major determinant of its inhibitory ability.

Resumo: Doença cardiovascular (DCV) está entre as principais causas de morbimortalidade e obesidade é um de seus fatores de risco. O melhor prognóstico de pacientes obesos gerou um paradoxo e a investigação de outros indicadores de obesidade como preditores de doença arterial coronariana (DAC). A associação de razão cintura-quadril e circunferência da cintura, marcadores de obesidade central, com doença coronariana determinada angiograficamente ainda não respondeu essa questão adequadamente. Além disso, a associação com circunferência do pescoço, marcador de obesidade visceral, não foi avaliada. Nesse estudo, avaliou-se a associação de obesidade – central, visceral e geral - com gravidade e extensão da doença coronariana. Métodos e Resultados: Estudo caso-controle foi conduzido em 376 pacientes, com 40 anos ou mais, com doença coronariana crônica, submetidos à cineangiocoronariografia eletiva. Índice de Massa Corporal (IMC), circunferência cintura, razão cintura-quadril (RCQ) e circunferência do pescoço foram aferidos. Doença coronariana significativa foi definida na presença de pelo menos 50% de estenose coronariana em um dos vasos epicárdicos (casos). Controles foram selecionados entre aqueles sem doença coronariana significativa. Foram identificados 155 casos e 221 controles e calculada odds ratio e IC 95%, com e sem controle para fatores de confusão. Houve predomínio de homens entre os casos, assim como idade entre 50-59 e mais de 70 anos. Razão cintura-quadril foi o principal preditor independente de DAC, seguido de circunferência do pescoço. Razão cintura-quadril associou-se fortemente com DAC nas análises univariada (OR= 3,7; IC 95%1,4-10,1 p=0,02) e o efeito tornou-se mais evidente na multivariada (OR= 4,0 IC 95% 1,3-12,1 p=0,03). Circunferência do pescoço só tornou-se significativamente associada no modelo multivariado (OR= 2,4 IC 95% 1,1-5,3 p= 0,04), assim como a categoria de obesidade do índice de massa corporal. Conclusões: Obesidade central, determinada por RCQ, é fator de risco independente para doença coronariana significativa, assim como circunferência do pescoço. / Introduction: Cardiovascular Disease is one of the main causes of morbimortality while the obesity is one of its risk factors. The best prognosis of obese patients has led to a paradox and the investigation of other obesity indicators as the coronary artery disease predictors (CAD). The association of waist-hip ratio and waist circumference, which are markers of central obesity with angiographically determined coronary disease has not yet answered that question adequately. In addition to that, the association with neck circumference as a marker of visceral obesity has not been evaluated. In this study, we have evaluated the association of central, visceral and general obesity with severity and extent of coronary artery disease. Methods and Results: A case-control study was conducted in 376 patients, aged 40 years or more, with chronic coronary disease, undergoing the elective cineangiography. Body Mass Index (BMI), waist circumference, waist-hip ratio (WHR), and neck circumference have been measured. Significant coronary disease was defined in the presence of at least 50% of coronary stenosis in one of the epicardial vessels or their branches, with diameter greater than three mm (cases). Controls have been selected among those without significant coronary disease. At the enrolment, 155 cases and 221 controls were identified. Odds ratios and the confidence intervals of 95% (95%CI) were calculated in the crude and multivariate analysis. There was a predominance of men in the cases, as well as aged 50-59 and over 70 years. The WHR was the main independent predictor of CAD, followed by the neck circumference. The waist-hip ratio was strongly associated with CAD in univariate analysis (OR= 3.7; 95%CI 1.4-10.1; P=0.02) and the effect became more evident controlling for confounding factors (OR = 4.0 95%CI 1.3-12.1; P=0.03). The neck circumference became significantly associated with CAD in the multivariate model (OR = 2.4 95% CI 1.1-5.3; P = 0.04), as well as obesity, in the category of BMI. Conclusions: Central obesity, as determined by WHR, was an independent risk factor for significant coronary disease, as well as the neck circumference.

Placas ateroscleróticas podem ser estáveis ou vulneráveis à formação de trombo, e os dois processos mais comumente envolvidos a este grave desfecho de trombose luminal são ruptura e erosão de placa. O conhecimento deste estado de vulnerabilidade pode ser importante na prática clínica. A parede arterial é um importante local de modificação proteica em resposta ao estresse. Proteínas em placas ateroscleróticas podem ser nitradas e seu acúmulo durante a aterogênese pode estar relacionado à captação de lipídios. Entre as consequências da nitração proteica, um importante marcador de estresse oxidativo, estão alterações na estrutura, atividade e susceptibilidade a proteólise e estas mudanças podem estar relacionadas a estabilidade da placa. Assim, este estudo teve como objetivo a quantificação e a verificação da distribuição tecidual de proteínas nitradas em segmentos de diferentes graus de vulnerabilidade de um mesmo indivíduo, e a correlação destes marcadores com o perfil histopatológico da placa. Segmentos de diferentes ramos coronários de 30 indivíduos, após infarto agudo do miocárdio fatal, foram estudados. Cinco tipos de placas ateroscleróticas de cada indivíduo foram selecionados, considerando o percentual de estenose e a presença ou não de trombo. Proteínas nitradas totais, linfócitos e macrófagos foram avaliados pela técnica de imuno-histoquímica. Os segmentos apresentando ruptura de placa demonstraram maior número de linfócitos e macrófagos nas camadas adventícia e íntima quando comparados a outros segmentos. A nitração estava relacionada com marcadores histológicos de vulnerabilidade da placa. Além disso, proteínas nitradas estavam diferentemente distribuídas nas camadas do vaso e altos níveis destas proteínas não foram implicados em todos os casos de formação de trombo, já que foi detectado em maior quantidade somente em rupturas de placa e não em casos de erosão de placa. Estes resultados mostram que estresse oxidativo é um importante atributo na diferenciação destes estados patológicos / Atherosclerotic plaques may be stable or vulnerable to thrombus formation. The two processes most commonly involved in this serious outcome of luminal thrombosis are rupture and erosion of the plaque. The knowledge of this vulnerable state of the plaque could be important in clinical practice. The artery wall is an important site of protein modification in response to stress. Proteins in atherosclerotic plaques may be nitrated, and its accumulation during atherogenesis may be related to lipid uptake. The consequences of protein nitration, an important marker of oxidative stress, are changes in its structure, activity and susceptibility to proteolysis and these changes may be related to plaque stability. Thus, this study aimed to quantify and investigate tissue distribution of nitrated proteins in coronary segments of different degrees of vulnerability from the same individual, and correlate these markers with plaque histopathological profile. Segments of coronary branches from 30 patients (after fatal acute myocardial infarct) were studied. Five different types of coronary atherosclerosis plaques from each subject were selected, considering the stenosis percentage and the presence or not of thrombus. Total nitrated protein, lymphocytes and macrophages were assessed by immunohistochemistry. The group presenting disrupted plaque exhibits higher macrophages and lymphocytes content in adventitia an intima layer when compared with other segments. Nitration was related with histological markers of plaque vulnerability. Furthermore, protein nitration was differently distributed in arteries layers and high levels of nitrated proteins were not implicated in all cases of thrombus formation, since it was detected in higher amounts only in ruptured and not in eroded plaques. These findings demonstrates that oxidative stress is an important characteristic in the differentiation of these pathophysiologic states

INTRODUÇÃO: Historicamente, os procedimentos de revascularização do miocárdio (cirúrgicos ou percutâneos) foram admitidos como opções terapêuticas efetivas para a proteção, em curto e médio prazo, do miocárdio isquêmico em pacientes portadores de doença arterial coronária. Todavia, não está estabelecido se tais procedimentos são essenciais para a preservação da função ventricular, nem se a ausência dos mesmos contribui para sua piora. OBJETIVOS: Avaliar a evolução da fração de ejeção (FEVE) em pacientes portadores de doença multiarterial coronariana crônica estável, e com função ventricular esquerda preservada, dez anos após terem sido submetidos a três diferentes estratégias terapêuticas: revascularização cirúrgica do miocárdio (RM), angioplastia coronária percutânea (ATC) ou tratamento medicamentoso (TM) isoladamente (subestudo do MASS II). MÉTODOS: Realizou-se o ecocardiograma transtorácico com doppler para avaliação da FEVE em pacientes portadores de DAC multiaterial estável no início do estudo e após dez anos das intervenções. O cálculo da FEVE foi realizado pelos métodos de Teichholz ou bidimensional. RESULTADOS: Dos 611 pacientes integrantes do estudo MASS II, 422 pacientes estavam vivos ao término de 10,32 (±1,43) anos de seguimento; destes, 108 pacientes do grupo TM, 111 do RM e 131 do ATC realizaram reavaliação ecocardiográfica da função ventricular. As principais características demográficas, clínicas e angiográficas foram semelhantes nos 3 grupos, bem como a ocorrência de infarto agudo do miocárdico (IAM). A FEVE foi semelhante entre os grupos no início do estudo (0,61 + 0,07, 0,61 + 0,08 e 0,61 + 0,09, respectivamente, para os grupos ATC, RM e TM [p=0,675]) e ao término do seguimento (0,56 + 0,11, 0,55 + 0,11 e 0,55 + 0,12, respectivamente, para os grupos ATC, RM e TM [p=0,675]). Observou-se redução da função ventricular (p<0,001) nos três grupos terapêuticos de forma semelhante (p=0,641). Outras variáveis, como gênero, diabetes, idade, padrão arterial, necessidade de ATC ou RM adicionais, não influenciaram a evolução da FEVE. Porém, a ocorrência de IAM foi responsável por acentuada queda da FEVE (delta de decréscimo de 18,29 + 21,22% e 6,63 + 18,91% para pacientes com e sem IAM, respectivamente [p=0,001]). Além disso, a presença de IAM prévio à randomização e IAM durante o seguimento foram associadas a desenvolvimento de disfunção ventricular, definida como FEVE < 45%. CONCLUSÃO: Pacientes do grupo clínico portadores de DAC multiarterial desprotegida pelas estratégias de revascularização não apresentaram prejuízo adicional na função ventricular em comparação ao observado nos grupos cirúrgico e angioplastia. Além disso, qualquer que tenha sido a estratégia terapêutica aplicada, a função ventricular permaneceu preservada na ausência de infarto agudo do miocárdio / BACKGROUND: Historically, myocardial revascularization procedures, either by coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), are assumed as effective therapeutic options for the protection of the ischemic myocardium. However, it is not established if those procedures are responsible for left ventricular function preservation, or even if their absence may contribute for the deterioration of left ventricular ejection fraction (LVEF). OBJECTIVES: to evaluate the evolution of LVEF in patients with chronic multivessel coronary heart disease and left ventricular function initially preserved, submitted to CABG, PCI or medical treatment (MT), after ten years of follow-up (MASS II substudy). METHODS: Transthoracic echocardiography was performed in patients with multivessel coronary heart disease, participants of MASS II trial, previously to randomization for one of the three possible therapeutic strategies (CABG, PCI and MT), and after 10 years of follow-up. LVEF was measured by the biplane method (Simpson) or alternatively by the Teichholz method. RESULTS: Of the 611 patients participants of MASS II trial, 422 were alive after a follow-up of 10.32 (±1.43) years. 350 had LVEF reassessed: 108 patients in MT group, 111 in CABG group and 131 in PCI group. Main baseline characteristics were similar among the three groups, including demographic, angiographic and laboratorial findings. The occurrence of acute myocardial infarction (AMI) was also similar among the 3 groups. There was no difference of LVEF either at the beginning (0.61 + 0.07, 0.61 + 0.08 e 0.61 + 0.09 respectively for PCI, CABG and MT, p=0.675) and the end of follow up (0.56 + 0.11, 0.55 + 0.11 e 0.55 + 0.12 respectively for PCI, CABG and MT groups, p=0.675). However, there was a slight, but significant reduction (P<0.001) of LVEF, similar on the three therapeutic groups (p=0.641). The impact of other variables over LVEF evolution, such as gender, age, diabetes, arterial pattern (including, left anterior descending coronary artery commitment) and additional revascularization, were also analyzed, with no influence on the evolution of LVEF. However, the presence of previous AMI (OR 2.50, 95% CI 1.40-4.45; p= 0.0007) and the occurrence of AMI during follow up (OR 2.73, 95% IC 1.25- 5.92; p=0.005) were associated with an increased risk of developing LVEF < 45%. Also, AMI during follow-up was responsible for a greater reduction of LVEF (reduction delta of 18.29 ± 21.22% and 6.63 ± 18.91%, respectively for patients with and without AMI during follow-up, p=0.001). CONCLUSION: Compared with PCI or CABG, the Medical group, with unprotected coronary disease by mechanical revascularization, showed no differences in left ventricular function after 10 years of follow-up. Moreover, regardless of therapeutic strategy applied, ventricular function remained preserved without AMI

Introdução:O diabetes mellitus tipo 2 (DM2) está associado ao aumento da mortalidade por doença arterial coronária (DAC). O DM2 afeta o metabolismo de lípides, levando à dislipidemia, caracterizada por hipertrigliceridemia e baixa concentração plasmática de HDL-colesterol. Transferências de lípides entre HDL e outras lipoproteínas são passos cruciais no metabolismo e função da HDL. Objetivo: Investigar se o desenvolvimento de DAC em pacientes com DM2 está associado com alterações na transferência de lípides para HDL. Métodos: Foram estudados 79 pacientes com DM2 portadores de DAC obstrutiva (DM2-DAC) e 76 pacientes com DM2 e artérias coronárias angiograficamente normais (DM2). Foram avaliados o perfil lipídico, apolipoproteínas, composição lipídica da HDL, dosagem de CETP e LCAT. No ensaio de transferência, as amostras de plasma foram incubadas por 1h a 37º com uma nanoemulsão artificial marcada com 3H-éster de colesterol e 14Cfosfolípides ou 3H -triglicérides e 14C-colesterol não esterificado. A quantificação da transferência de lípides da nanoemulsão doadora para a HDL foi feita após a precipitação da fração não HDL. O tamanho da HDL foi medido por laser light scattering. Resultados: Os pacientes DM2-DAC apresentaram maior concentração de colesterol total (DM2-DAC=218±48; DM2=193±36; p < 0,001), LDL-C (147±44 vs 124±33; p < 0,001) e apoB (103,1±20,4 vs 96,0 ± 19,5; p = 0,03) que o grupo sem DAC. Os grupos não mostraram diferença com relação à concentração plasmática de triglicérides (DM2-DAC=171 ± 73; DM2=154 ± 70; p=0,1) e HDL-C (41±9 vs 38±8; p=0,07). A transferência de éster de colesterol (4,0 ± 0,6 vs 4,3 ± 0,7; p=0,005) e de colesterol não esterificado (7,6 ± 1,2 vs 8,2±1,5; p=0,006) foi menor no grupo com DAC, porém esse grupo teve maior concentração de colesterol não esterificado no plasma (36,3 ± 8,0 vs 33,6±6,5 ;p=0,02). A concentração de CETP foi menor no grupo DM2DAC (2,1±1,0 vs 2,5 ±1,1; p=0,02 ). O diâmetro das partículas de HDL não diferiu entre os grupos (8,9 ± 1,2 vs 9,0±0,6; p=0,4), nem a composição lipídica da HDL (éster de colesterol: 52,2 ± 10,8 vs 50,6 ± 10,7; p=0,38; colesterol não esterificado: 9,0 ± 2,8 vs 8,4 ± 2,7; p=0,19; triglicérides: 13,4 ± 3,9 vs 12,4 ± 3,9; p=0,11e fosfolípides:77,2 ± 16,7 vs 78,8 ± 20,5; p=0,60). A atividade da enzima LCAT não diferiu entre os grupos (1,34 ± 0,12 vs 1,33 ± 0,10; p=0,9). As transferências de todos os lípides apresentaram correlação entre si. Na análise multivariada, a presença de DAC influenciou a transferência de éster de colesterol, quando ajustado para HDL-C, apoA1, CETP massa e LDL-C (r2=0,5, p=0,03) e a transferência de colesterol não esterificado, quando ajustado para apoA1, apoB, LCAT, glicemia, idade e sexo (r2 = 0,7, p = 0,003). Conclusão: Na amostra estudada, pacientes diabéticos portadores de DAC apresentam menor transferência de colesterol para HDL comparados com os pacientes diabéticos sem DAC obstrutiva / Aim: Type 2 diabetes mellitus (DM2) is associated with morbidity and mortality secondary to coronary artery disease (CAD). DM2 affects lipid metabolism, and diabetic dyslipidemia is characterized by increased levels of tryglicerides and reduced levels of HDL-cholesterol. Lipid transfer between HDL and the other lipoproteins is a crucial step in HDL function and metabolism. Objective: The purpose of this study was investigate whether the susceptibility of patients with type 2 diabetes mellitus to develop CAD is related with alterations in lipid transfers to HDL. Methods: 79 patients with DM2 and obstructive CAD (DM2- CAD) and 76 with DM2 (DM2 group) and angiographic normal coronary arteries were studied. Lipid profile, apolipoproteins, HDL lipid composition, CETP and LCAT activity were evaluated. In the lipid transfer assay, fasting plasma samples were incubated for 1h at 37°C with a donor artificial nanoemulsion labeled with 3H -cholesteryl-esters and 14C-phospholipids or 3H-triglycerides and 14C-unesterified cholesterol. Radioactive lipids transferred from the donor nanoemulsion to HDL were quantified in the supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. HDL size was measured by laser light scattering. Results: In DM2-CAD, total cholesterol (DM2- DAC=218 ± 48; DM2=193±36; p < 0,001), LDL-C (147 ± 44 vs 124±33; p < 0,001) and apoB (103,1±20,4 vs 96,0±19,5; p=0,03) were higher than in DM2 group. The groups showed no differences with respect to plasma triglycerides levels (DM2-DAC=171± 73; DM2=154 ± 70; p=0,1) nor HDL-C (41 ± 9 vs 38±8; p=0,07). DM2-CAD showed diminished transfer to HDL of esterified cholesterol (4,0±0,6 vs 4,3 ± 0,7; p = 0,005) and unesterified cholesterol (7,6 ± 1,2 vs 8,2 ± 1,5; p=0,006). However, the DM2-CAD group showed higher levels of plasmatic unesterified cholesterol (36,3±8,0 vs 33,6±6,5 ;p=0,02). CETP mass was lower in the DM2- CAD group (2,1 ± 1,0 vs 2,5 ± 1,1; p=0,02 ). HDL particle diameter was not different between groups (8,9±1,2 vs 9,0 ± 0,6; p=0,4) neither its lipid composition (esterified cholesterol: 52,2 ± 10,8 vs 50,6 ± 10,7; p=0,38; unesterified cholesterol: 9,0 ± 2,8 vs 8,4 ± 2,7; p=0,19; triglycerides: 13,4 ± 3,9 vs 12,4 ± 3,9; p=0,11; phospholipids: 77,2 ± 16,7 vs 78,8 ± 20,5; p=0,60). LCAT activity was not different in the two groups (1,34±0,12 vs 1,33±0,10; p=0,9). In multivariate analysis, DAC influenced cholesteryl ester transfer, when adjusted to HDL-C, apoA1, CETP mass and LDL-C (r2=0,5, p=0,03), and unesterified cholesterol transfer, when adjusted to apoA1, apoB, LCAT, glycemia, age and sex (r2=0,7, p=0,003). Conclusion: In these sample, DM2-CAD patients show diminished cholesterol transfer to HDL particles when compared to diabetic patients without obstructive CAD

No description available.

Les nucléotides cycliques (NC) apparaissent comme des régulateurs majeurs du tonus vasculaire. Produits dans les cellules musculaires lisses (CMLs) par les cyclases, les NC agissent par l’intermédiaire des protéines effectrices qui modulent de nombreux mécanismes régulateurs de la vasomotricité. Les phoshodiestérases (PDEs) qui dégradent les NC assurent le contrôle spatiotemporel de leur réponse biologique. L’objectif de mon travail était de préciser les mécanismes par lesquels le tonus artériel est contrôlé par certaines PDEs. J’ai réalisé cette exploration en utilisant des artères coronaires ou mésentériques de rat, en situation physiologique puis dans un modèle d’insuffisance cardiaque (IC) chronique.Dans la première partie de mon travail, nous nous sommes intéressés au mécanisme par lequel les PDE3 et PDE4 régulent le tonus de l’artère coronaire.Par une approche expérimentale plus intégrée de réactivité vasculaire sur artère coronaires isolées, nous avons montré l’importance du canal potassique BK(Ca) dans l’effet relaxant des inhibiteurs de PDE3 et PDE4. De plus, nous avons constaté une contribution différentielle de ces canaux selon le mode de stimulation de la génération d’un NC, l’AMPc. A l’échelle de la CML, notre étude a permis de suggérer l’existence d’un signalosome impliquant les PDE3/PDE4 et du canal potassique BK(Ca), indiqué par la technique de Proximity Ligation Assay. En accord avec cette hypothèse, le contrôle des BK(Ca) par ces PDEs a pu être mis en évidence par la technique du Patch-Clamp. De manière intéressante, la contribution du couplage fonctionnel entre le canal BKCa et les PDE3 et PDE4 n’a pas été retrouvée dans les artères isolées de rats atteints d’IC. Ceci pourrait être expliqué par une diminution de l’expression des canaux BK(Ca) ainsi que, au moins partiellement, par une raréfaction de leur localisation à proximité de la PDE4B.Dans la deuxième partie de mon travail nous avons exploré les rôles des PDE3, PDE4 et de la PDE2 en particulier, dans la régulation du tonus de l’artère mésentérique de rats atteints d’IC, en comparaison aux rats contrôles. En effet, la contribution de la PDE2 est suggérée par la capacité d’un inhibiteur sélectif de cette enzyme à diminuer la réponse des artères isolées à une stimulation vasocontractante. Nous avons ensuite exploré les effets de cet inhibiteur dans d’autres types de réponses impliquant les NC.L’ensemble de ces travaux ajoute un niveau de complexité à la compréhension des mécanismes de la régulation de la vasomotricité des artères de résistance par les PDEs. Les altérations de cette voie de signalisation que nous avons mises en évidence dans l’IC pourraient contribuer à la dysfonction vasculaire qui accompagne la maladie. / Cyclic nucleotides (CN) appears to be important regulator of vascular tone. Produced in smooth muscle cells (SMCs) by cyclases, CN act through activation of key effectors involved in the regulation of vascular tone. Phoshodiesterases (PDEs), which degrade CN, provide spatiotemporal control of their biological responses. The aim of my work was to understand how vascular tone is controlled by some PDEs and how it is altered during heart failure (HF). For this, I used rat coronary and mesenteric arteries.In the first part of my work, we were interested in defining the contribution of PDE3 and PDE4 in the regulation of coronary tone. Using vascular reactivity technique, we demonstrate the importance of large-conductance Ca2+-activated potassium channel (BK(Ca)) channel in the relaxant effect of PDE3 and PDE4 inhibitor. Moreover, their contribution was different depending on the mode of cAMP production, a type of CN. At the cellular level, Proximity Ligation Assay experiments suggest the existence of a signalosome that involves PDE3/PDE4 andBK(Ca). According to this result, the control of BK(Ca) activity by these PDEs was demonstrated using the Patch-Clamp technique. Interestingly, the contribution of the functional coupling involving the BK(Ca) and PDE3/PDE4 is lost during HF. This may be explained by the decrease of BK(Ca) expression and [BK(Ca)-PDE4B] duplex signal in coronary arteries isolated from HF rat.In the second part of my work, we investigated the role of PDE3, PDE4 and PDE2 particularly, in the regulation of rat mesenteric artery tone during HF. In fact, PDE2 selective inhibitor, decreased the contractile response of isolated arteries. Then, we investigated the effect of PDE2 inhibition in other pathway that involve CN.Our findings underline the complexity of PDEs in the regulation of resistance artery tone. During HF, some CN signaling pathway are impaired leading to vascular dysfunction which can aggravate the pathology.

Hjärt- och kärlsjukdomar är den största dödsorsaken i världen. En av behandlingarna som kan ges vid detta är koronar bypass operation. Väntan inför denna operation kan upplevas oviss och skapa oro hos patienten. Syftet med litteraturstudien var att undersöka patientens upplevelse i väntan på koronar bypass operation. Metod: Studien genomfördes som en allmän strukturerad litteraturstudie med induktiv ansats där sex kvalitativa, en kvantitativ samt en artikel med mixad metod erhölls. Data bearbetades genom en innehållsanalys. Resultat: Resultatet visade att patienter upplever såväl emotionell som somatisk påfrestning i väntan på koronar bypass operation. De mest framträdande upplevelserna var att patienterna upplevde ängslan och oro, ovisshet, rädsla och fysiska restriktioner. Dessa upplevelser mynnade ut till två teman den emotionella väntan och den somatiska väntan. Konklusion: I väntan på koronar bypass operation var de mest framträdande upplevelserna ovisshet samt ängslan och oro. För att reducera ovissheten, ängslan och oron var det av största vikt att sjuksköterskan arbetade personcentrerat. En sjuksköterskeledd intervention samt möjlighet att prata med tidigare koronar bypass operation patienter visade en signifikant reducering av den emotionella påfrestningen. En ökad förståelse för patienters upplevelse i väntan på koronar bypass operation är av stor vikt för att möjliggöra personcentrerad omvårdnad. / Cardiovascular disease is the leading cause of death in the world. One of the treatments for this is to undergo a coronary artery bypass graft. The waiting time before surgery causes uncertainty and worry in some patients. The aim was to examine patients’ experience while waiting for coronary artery bypass. The Method used was a general structured literature study with an inductive approach, where sixarticles with a qualitative approach, one quantitative and one with mixed method were found. The data was processed through a content analysis. The Result showed that patients experience both emotional and somatic stress while waiting for coronary artery bypass surgery. The most dominant experiences and emotions that patients felt were anxiety, uncertainty, fear, and physical restrictions. These experiences and emotions resulted in two themes Emotional waiting and Somatic waiting. TheConclusion showed to reduce uncertainty and anxiety it was of the utmost importance that the nurse applied person-centered care. A nurse-led intervention as well as the opportunity to talk with former coronary artery bypass patients showed a significant reduction in emotional strain. An increased understanding of patient´s experience while waiting for coronary artery bypass is of great importance to enable person-centered care.