Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

Made available in DSpace on 2014-07-29T15:29:19Z (GMT). No. of bitstreams: 1 Dissertacao CARLA FERREIRA.pdf: 3775197 bytes, checksum: bdad663383a24c725cbe0056da09f27e (MD5) Previous issue date: 2009-12-08 / Introduction: cardiovascular risk factors (CVRFs) are highly prevalent in and have an impact on elderly people s morbidity and mortality which is still unknown among elderly users of the National Health System (SUS). Objective: to investigate the prevalence of CVRFs in elderly basic care users in the Goiânia, Goiás SUS. Methodology: a cross-sectional study with multi-stage sampling; a household survey of 418 people over 60 years old who were SUS basic care users in Goiânia. Socio-economic, demographic, lifestyle, weight, height, waist circumference, blood pressure and medication use data were collected. The CVRFs under investigation were arterial hypertension, diabetes mellitus, total obesity, central obesity, dyslipedemias, smoking, sedentarism and alcohol consumption. The Chi-square test was used to analyze associations at a 5% level of significance. Results: the prevalences for CVRFs were 80.4% for arterial hypertension, 83.3% for central obesity, 59.8% for sedentarism, 32.2% for total obesity, 23.4% for dyslipidemias, 19.1% for diabetes mellitus, 10.0% for smoking and 5.9% for alcohol consumption. As far simultaneity is concerned, 2.4% of the elderly did not present any CVRFs. The simultaneity of three or more CVRFs occurred in 65% of the elderly people in the study and was more frequent among women. Conclusion: the CVRFs occurred simultaneously in more than half of the elderly under study. The most prevalent CVRFs were arterial hypertension, central obesity and sedentarism. It is necessary to intensify health promotion and cardiovascular disease prevention strategies among elderly users of SUS basic care in Goiânia, mainly among those with CVRF simultaneity. / Introdução: os fatores de risco cardiovascular (FRCV) apresentam alta prevalência e causam impacto na morbimortalidade de idosos, ainda desconhecido entre idosos usuários do Sistema Único de Saúde. Objetivo: investigar a prevalência de FRCV em idosos usuários da atenção básica do Sistema Único de Saúde (SUS) de Goiânia-Goiás. Metodologia: estudo transversal com amostragem em múltiplos estágios, realizado por meio de inquérito domiciliar com 418 idosos acima de 60 anos, usuários do SUS da atenção básica de Goiânia. Foram coletados dados socioeconômicos, demográficos, estilo de vida, peso, altura, circunferência da cintura, pressão arterial e uso de medicamentos. Os FRCV investigados foram: hipertensão arterial, diabetes mellitus, obesidade total, obesidade central, dislipidemias, tabagismo, sedentarismo e consumo de bebida alcoólica. Utilizou-se o teste do Qui quadrado para análises das associações, com significância de 5%. Resultados: as prevalências dos FRCV foram 80,4% de hipertensão arterial, 83,3% de obesidade central, 59,8% de sedentarismo, 32,2% de obesidade total, 23,4% de dislipidemias, 19,1% de diabetes mellitus, 10,0% de tabagismo e 5,9% de consumo de bebida alcoólica. Quanto à simultaneidade 2,4% dos idosos não apresentaram nenhum FRCV. A simultaneidade de três ou mais FRCV ocorreu em 65% dos idosos, sendo mais freqüente entre as mulheres. Conclusão: os FRCV ocorrem de forma simultânea em mais da metade dos idosos, sendo que os mais prevalentes foram hipertensão arterial, obesidade central e sedentarismo. É preciso intensificar as estratégias de promoção da saúde e prevenção de agravos cardiovasculares em idosos usuários da atenção básica do SUS de Goiânia, principalmente entre aqueles com simultaneidade de FRCV.

Introdução: A hipertensão arterial é de causa multifatorial, envolvendo hábitos de vida e estilos de vida inadequados como o consumo excessivo de bebida alcoólica que propiciam a elevação dos níveis pressóricos. Além disso, os sintomas relacionados ao transtorno mental comum também podem se associar ao estado de saúde, provocando mais danos ao sujeito com hipertensão arterial. Diante disso, o presente estudo teve como objetivo principal identificar associação entre a ocorrência de hipertensão arterial com o consumo de bebidas alcoólicas e a presença de transtorno mental comum em indígenas das aldeias Muras, residentes em região rural e urbana. Casuística e Métodos: Estudo transversal, de base populacional, com 455 indígenas Mura residentes no município de Autazes, Amazonas, Brasil. Foi aplicada a entrevista semi-estruturada com questões referentes aos dados socioeconômicos e educacionais, hábitos de vida, história clínica, histórico familiar, além dos questionários Alcohol Use Disorders Identification Test (AUDIT) e Self-Reporting Questonnaire (SRQ-20), para avaliar o consumo de álcool e presença de transtorno mental, respectivamente. A pressão arterial foi medida com aparelho automático de braço validado. Foram realizadas três medidas e usada a média das duas últimas medidas. Realizaram-se ainda, medida do peso, altura, circunferência do pescoço, circunferência da cintura, avaliação de bioimpedância; glicemia, triglicérides e colesterol com medida capilar. Na análise bivariada, foi testada a associação entre hipertensos, separadamente, com os dois desfechos: consumo de bebidas alcoólicas e a presença de transtorno mental comum explorando especialmente, os aspectos relacionados à hipertensão arterial. Foi ajustada a regressão de Poisson com variância robusta, para ambos os desfechos, com modelagem em stepwise backward automatizado, tendo como critério de entrada, p<0,20 e de significância no modelo final, p0,05. Utilizou-se como estimativa, as razões de prevalência e respectivos intervalos de confiança de 95%. Resultados: A maioria dos participantes era do sexo feminino (57,8%), com 42,10 (16,74) anos, vivendo com companheiro (74,7%) e cerca de quatro filhos por família, baixo nível de escolaridade Analfabeto/Fundamental incompleto (41,1%) e renda até dois salários mínimos (85,0%). A prevalência de hipertensão arterial foi de 26,6%, tabagismo (20,4%) e ser sedentário/irregularmente ativo (52,8%). O consumo de bebida alcoólica foi de 40,2%, sendo 13,4% classificados como alto risco para dependência alcoólica, e maior na área rural em comparação à urbana (57,3% vs 22,2%) p<0,001. Destacam-se os seguintes aspectos do uso abusivo de álcool: sentimento de culpa/remorso (45,9%); amnésia repentina por não lembrar o ocorrido na noite em que bebeu (31,7%); além de machucar-se ou sentir-se prejudicado por causa da bebida (29,6%); preocupação por parte de parentes, amigos ou profissionais de saúde, que aconselharam o entrevistado a interromper o consumo (51,5%). Não houve associação entre a presença e consumo de bebida alcoólica (23% e 26%). Os indígenas com diagnóstico de hipertensão referida, faziam menos uso de bebida alcoólica (14,2%vs 85,8%, p=0,009), porém nas ocasiões em que bebiam, ingeriam maior quantidade, comparado com os que não referiram hipertensão [55,3(72,2) vs 33,3(62,2) gramas de Etanol p=0,008]. A prevalência de transtorno mental comum foi de 45,7%, com destaque para os seguintes itens: referência de dores de cabeça frequentes (69,5%), sentir-se nervoso, tenso ou preocupado (66,2%), ter se sentido triste ultimamente (56,0%), dormir mal (55,2%) e ter sensações desagradáveis no estômago (42,9%). Além disso, destaca-se que 7,3% referiram ideia de acabar com a própria vida e 4,2% sentiram-se incapazes de desempenhar papel útil. Após análise ajustada a razão de prevalência após análise ajustada (Razão de prevalência, IC-95%), verificou-se associação positiva entre ingestão de bebida alcoólica e sexo masculino (2,72, IC-2,12-3,48), tabagismo (1,29, IC-1,06-1,56) e morar na zona rural (2,09, IC-1,61-2,72). Porém, a ação foi protetora para idade (0,98, IC-0,98-0,99), consumo de alimentos in natura (0,97, IC-0,95-0,99), e ausência de dislipidemias (0,75, IC-0,62-0,9). Entre os que apresentaram transtorno mental comum, a hipertensão arterial identificada esteve presente em 30,3% e o consumo de álcool uma vez ao mês em 22,1%. Após a análise ajustada (Razão de prevalência, IC-95%) verificou-se associação positiva entre o transtorno mental comum e a zona de moradia urbana (1.25, IC-1,02-1,54), não sabia que tinham antecedentes para diabetes (1.56, IC-1,24-1,96) e a ingestão de bebida alcoólica (1.01, IC-1,00-1,02). Porém, foi ação protetora não ter antecedentes pessoais de cardiopatia (0.59, IC-0,48-0,73). Conclusão: Observou-se que a presença de hipertensão arterial, consumo de bebida alcoólica e de transtorno mental comum foram elevados nos indígenas da etnia Mura. Esses achados podem ser decorrentes da aproximação e convivência entre indígenas e não indígenas favorecendo mudanças culturais, especialmente de hábitos e estilos de vida, com aumento do risco de doenças crônicas não transmissíveis. / Background: The arterial hypertension has a multifactorial disorder, including unappropriated habits and lifestyle as the excessive consumption of alcoholic beverages that may increase the blood pressure. Additionally, the symptoms related to the common mental disorder may be also associated with the health status, producing even more damages to the hypertensive subjects. Thus, this study aimed to identify the association of arterial hypertension occurrence with alcoholic beverages consumption and presence of common mental disorder in Indigenous from Mura villages, who live in rural and urban zones. Casuistic and Methods: Its a cross-sectional investigation, with demographic base, conducted with 455 Mura Indigenous from Autazes, Amazon, Brazil. Through a semi-structured interview, we gathered data about sociodemographic and educational profile, lifestyle, clinical records, family antecedents. In this occasion, the Alcohol Use Disorders Identification Test (AUDIT) and the Self-Reporting Questionnaire (SRQ-20) were applied to assess respectively the alcohol consumption and the presence of common mental disorder. The blood pressure was measured with an arm automatic device, validated for this goal, being three measures taken and, from the two last of them, a mean was obtained. Furthermore, we gathered weight, height, neck circumference, waist circumference, bioimpedance, glycemia, triglycerides and cholesterol, capillary measure for the last ones. In the bivariate analysis, we analyzed the association between hypertensive persons and the both outcomes- the alcohol consumption and the presence of common mental disorder, emphasizing the issues hypertension-related issues. The Poison regression, with robust variance, was adjusted for both outcomes, with a modelling in automatized stepwise backward, being p<0,20 the entrance criteria and p<0,05 the significance level for the final model. As estimative, we used the odds ratios and their respective confidence intervals of 95%. Results: Most were females (57,8%), with mean age of 42,2(16,74) years, living with a partner (74,7%), with about four children per family, poor educational level- Illiterate/Incomplete Basic (41,1%) and income of up two minimum wages (85,0%). 26,6% of the sample had hypertension, 20,4% were smokers and 52,8% were sedentary/irregularly active. Alcohol consumption was of 40,2%, with 13,4% showed high risk for alcohol addiction, and the consumption was higher in rural area in comparison with the urban one (57,3% vs 22,2%) p<0,001. We emphasize the following aspects of alcohol abuse: feeling of guilty and remorse (45,9%); abrupt amnesia for not remembering what happened in the night that they had drunk (31,7%); feeling hurt or impaired due to the drink consumption (29,6%); concerns from relatives, friends or healthcare professionals who advised the interviewed to interrupt the consumption (51,5%). There was not association between presence and alcoholic beverages consumption (23% and 26%). Indigenous diagnosed with referred arterial hypertension drank less alcoholic beverages (14,2%vs 85,8% p=0,009), but, when they drank, they had a larger amount than those with referred hypertension [55,3(72,2) vs 33,3(62,2) grams of Ethanol p=0,008]. The common mental disorder was identified in 45,7% of the individuals, being highlighted the following items: reporting of frequent headaches (69,5%), feeling nervous, anxious or worried (66,2%), feeling sad in the last days (56,0%), sleeping badly (55,2%) and having upset stomach (42,9%). Additionally, 7.3% reported the idea of committing suicide, and 4,2% felt themselves unable to play a useful role. We verified positive association between alcoholic beverage consumption and male gender (2.72, CI-2,12-3,48); smoking (1.29, CI-1.06-1.56); and living in rural area (2.09, CI-1.61-2.72). However, the action was protective for the age (0.98, CI-0,98-0,99), intake of natural foods (0.97, CI-0,95-0,99), and absence of dyslipidemias (0.75, CI-0,62-0,9). Among those diagnosed with common mental disorder, the arterial hypertension was found in 30,3% and the alcohol consumption once a month in 22,1%. We observed a positive association of common mental disorder and: living in the urban area (1.25, CI-1,02-1,54); unknowing the antecedents for diabetes (1.56, CI-1,24-1,96); and the alcohol consumption (1.01,CI-1,00-1,02). However, the absence of personal background of heart diseases was not protective (0.59, CI-0,48-0,73). Conclusion: We observed that the presence of arterial hypertension, alcoholic beverages consumption and common mental disorder were high in the Mura ethnicity. This finding may be explained for the approach and interaction among Indigenous and non-Indigenous, which favors cultural changes, especially in habits and lifestyle, increasing the risk of non-transferable chronic diseases.

Abstract The prevalence of self-reported obstructive sleep apnea syndrome (OSAS), habitual snoring (HS), daytime sleepiness (DS) and restless legs syndrome (RLS), and their associations with cardiovascular risk factors and depressive symptoms as well as the natural course and associated factors of habitual snoring and restless legs syndrome over a ten-year period were studied. Two different birth cohorts in Northern Finland were investigated. In the Oulu 35 longitudinal research programme study subjects participated in two subsequent surveys conducted in 1996–1998 and 2007–2008 (61–63 and 72–73 years old subjects, respectively). The Oulu 45 study population was examined in 2001–2002 (56–57 years old subjects). The data were gathered by questionnaires, as well as laboratory and clinical measurements. In the Oulu35 study, of the 831 baseline participants, 593 (73%) participated in the first follow-up in 1996–1998 and 457 (55%) participated in both follow-up studies. In the Oulu 45 study, the target population comprised 1 332 subjects, 995 (75%) of whom participated. The prevalence of OSAS was 8% in the 56–57 year-old population, 4% in the 61–63 year old population, and 3% in the 72–73 year old population. These figures were 31%, 26% and 19% for HS, 16%, 9% and 11% for DS, and 18%, 21% and 15% for RLS, respectively. In a ten-year period, half of those who snored in 1996–1998 stopped snoring, and half of those who suffered from restless legs 3–7 nights/week in 1996–98 suffered from this syndrome less than once a week in 2007–2008. The 10-year incidence of new cases of both HS and RLS was 7%. In subjects aged 56–57 and 61–63, the components of the metabolic syndrome and depressive symptoms associated with OSAS and HS, while in the follow-up study, the role of these associations diminished. Male gender was the strongest predictor of the new cases of HS, while depressive symptoms and waist circumference predicted the permanence or incidence of HS. Depressive symptoms, DS and, weakly, waist circumference were associated with RLS in both the 56–57 year-old and in 61–63 year-old populations. Depressive symptoms were also predictive of the permanence and incidence of new RLS cases. Waist circumference also predicted new cases of RLS in the 72–73 year-old population. Sleep disorders were quite common in 56–73 year-old subjects and their prevalence seemed to diminish as subjects aged. The components of metabolic syndrome associated with sleep disorders in middle-aged subjects, but these associations lost their significance in older age groups. Depressive symptoms predicted incidence of restless legs syndrome. / Tiivistelmä Tutkimuksessa selvitettiin unenaikaisten hengityshäiriöiden, päiväaikaisen väsymyksen ja levottomien jalkojen esiintyvyyttä ja yhteyksiä sydän- ja verisuonitautien riskitekijöihin sekä depressioon. Jokaöisen kuorsaamisen ja levottomien jalkojen luonnollista kulkua ja siihen vaikuttavia tekijöitä selvitettiin 10 vuoden seuranta-aikana. Tutkimusaineisto koostui kahdesta eri-ikäisestä pohjoissuomalaisesta väestöstä. Oulu35-seurantatutkimukset tehtiin vuosina 1996–1998 ja 2007–2008 (61–63- ja 72–73-vuotiaat tutkittavat). Oulu45-poikkileikkaustutkimus tehtiin vuosina 2001–2002 (56–57-vuotiaat tutkittavat). Aineisto kerättiin kyselylomakkeilla, laboratorio- ja kliinisillä tutkimuksilla. Oulu35-tutkimuksessa 593 henkilöä (73&#160;%) 831 kutsutusta osallistui ensimmäiseen seurantatutkimukseen v. 1996–1998 ja molempiin seurantatutkimuksiin osallistui 457 (55&#160;%) henkilöä. Oulu45 -tutkimukseen osallistui 995 henkilöä (75&#160;%) 1332 kutsutusta. Obstruktiivisen uniapnean esiintyvyys 56–57-vuotiaalla väestöllä oli 8&#160;%, 61–63-vuotiailla 4&#160;% ja 72–73-vuotiailla 3&#160;%. Jokaöisen kuorsaamisen esiintyvyys oli vastaavissa ikäluokissa 31&#160;%, 26&#160;% ja 19&#160;%, päiväaikaisen väsymyksen 16&#160;%, 9&#160;% ja 11&#160;% ja levottomien jalkojen 18&#160;%, 21&#160;% ja 15&#160;%. Kymmenen vuoden seurannassa jokaöinen kuorsaaminen vähentyi puoleen niillä henkilöillä, jotka kuorsasivat v. 1996–1998. Vastaavasti 10 vuoden kuluttua niillä henkilöillä, joilla esiintyi levottomia jalkoja 3–7 yönä viikossa v. 1996–1998, esiintyvyys oli vähentynyt alle 1 kertaan viikossa puolella tutkituista. 10 vuoden ilmaantuvuus sekä jokaöiselle kuorsaamiselle että levottomille jaloille oli 7&#160;%. Metabolisen oireyhtymän osatekijät ja depressiiviset oireet olivat yhteydessä obstruktiiviseen uniapneaan ja jokaöiseen kuorsaamiseen sekä 56–57-vuotiailla että 61–63-vuotiailla. Kymmenen vuoden seurannassa näiden tekijöiden vaikutus näytti kuitenkin vähentyvän. Miessukupuoli ennusti vahvimmin jokaöisen kuorsaamisen ilmaantuvuutta. Myös depressiiviset oireet ja vyötärönympärys ennustivat jokaöisen kuorsaamisen ilmaantuvuutta ja pysyvyyttä. Depressiiviset oireet, päiväaikainen väsymys ja vyötärönympärys olivat yhteydessä levottomien jalkojen esiintyvyyteen sekä 56–57- että 61–63-vuotiaassa että väestössä. Depressiiviset oireet ennustivat myös levottomien jalkojen ilmaantuvuutta ja tilan pysyvyyttä ja vyötärönympärys levottomien jalkojen ilmaantuvuutta 72–73-vuotiaana. Unihäiriöt olivat varsin yleisiä 56–73-vuotiaissa väestöissä, ja niiden ilmaantuvuus näyttäisi vähentyvän iän mukana. Metabolisen oireyhtymän osatekijät olivat yhteydessä unihäiriöihin keski-ikäisillä, mutta vanhemmissa ikäluokissa näiden yhteyksien merkitys väheni. Depressiiviset ennustivat levottomat jalat -oireyhtymän ilmaantuvuutta.

Les professionnels de l'analyse de la pratique et de l'organisation des soins interviennent dans un système complexe où interagissent des facteurs biologiques, culturels et sociaux. Ce travail de recherche porte sur les vécus du patient cardiovasculaire entrant dans un programme d'éducation thérapeutique, suite à un évènement aigu (infarctus du myocarde ou accident vasculaire cérébral). Il se justifie par la nécessité de comprendre le phénomène des récidives, rechutes et retours à l'hospitalisation malgré une prise en charge informative et éducative des facteurs de risques cardiovasculaires (tabagisme, sédentarité, mauvaise alimentation) durant l'hospitalisation initiale. Notre principal objectif est donc de comprendre ces récidives, rechutes et retours à l'hospitalisation des patients cardiovasculaires autrement que le résultat d'une non-observance. Cette recherche de type qualitatif est menée au Centre Hospitalo-Universitaire de Clermont-Ferrand (service de cardiologie court séjour) et à la clinique cardiopneumoloique de Durtol (centre de soins de suite et de réadaptation). La recherche est basée sur 22 situations d'observations de pratiques professionnelles, 9 entretiens centrés avec les professionnels dans ces 2 sites ci-dessus et 31 entretiens semi-directifs avec les patients. Ces enquêtes sont complétées par une analyse de la littérature française et anglo-saxonne, dans le domaine de l'éducation thérapeutique, de l'observance et du changement des comportements. En termes de résultats, la recherche présente les récidives, rechutes et retours à l'hospitalisation court séjour des patients comme le résultat d'une prise en charge inadaptée à leurs besoins. Des discordances de temps, de vécus et de ressentis entre professionnels de santé et patients durant l'hospitalisation initiale, l'inadaptation structurelle du court séjour, la discontinuité de la prise en charge et les ruptures de cohérence en fonction des différents niveaux de complexité (court séjour, centre de soins de suite et de réadaptation et chez les médecins traitants), mais surtout la confusion entre éducation du patient et information du patient, rendent les prescriptions médicales et soignantes en matière de changement des comportements à risques difficilement observables par les patients. Le format actuel de la relation et des interactions patients/professionnels de santé durant les soins, ne favorise pas l'implication et la participation active des patients dans leur prise en charge. En conclusion, nous retenons que les éléments qui influencent les comportements des patients vis-à-vis de leurs traitements ne relèvent pas seulement d'un apprentissage, mais de leur vécu et ressentis et également de leurs interactions avec les professionnels de santé. La prise en charge informative et éducative des facteurs de risques occulte parfois l'aspect relationnel de cette thérapeutique et les capacités cognitives et émotives des patients. Elle devrait suivre une double évolution : celle du patient (ses émotions, ses attentes, ses projets de vie…) et celle de la pathologie. Ce travail cherche également à répondre à la question suivante : en quoi et comment une approche socio-anthropologique permet-elle de comprendre les comportements des patients d'une part et des professionnels de santé d'autre part dans un contexte d'ETP en court séjour ? Il milite pour une reconnexion entre sciences sociales et sciences médicales et soignantes dans le système de soin et de santé français et montre l'apport considérable mais encore trop peu exploité des sciences sociales dans ce domaine. / The professionals of the practice analysis and care organization take part in a complex system where biological, cultural and social factors interact. This research task focuses on the experiences of the cardiovascular patient entering a therapeutic education program, after an acute event (myocardial infarction or stroke). It is justified by the need to understand the phenomenon of recurrence, relapse and hospitalization returns despite an informative and educational treatment in cardiovascular risk factors (smoking, physical inactivity, poor nutrition) during the initial hospitalization. Our main goal is therefore to understand these recurrences, relapses and hospitalization returns of cardiovascular patients other than the result of non-compliance. This qualitative research is carried out at the University Hospital Center of Clermont-Ferrand (Cardiology Department short stay) and at the cardio-pneumologic clinic of Durtol (follow-up and rehabilitation care center). The research is based on 22 observation situations of professional practices, nine focused interviews with professionals in these two sites above and 31 semi-structured interviews with the patients. These surveys are supplemented by an analysis of the French and Anglo-Saxon literature in the field of therapeutic education, compliance and behaviours change. In terms of results, the research presents the recurrences, relapses and returns to patients' short stay hospitalization as the result of an inappropriate care to their needs. Time discrepancies, experiences and felt between health professionals and patients during the initial hospitalization, inadequate structural short stay, the discontinuity of care and the inconsistencies in accordance with different levels of complexity (short stay, follow-up and rehabilitation care center and at the attending physicians', but mostly the confusion between the patient's education and the patient's information, makes medical and nursing requirements in terms of the change of risky behaviours hardly observable by patients. The current format of the relationship and the interactions patient/health professionals during the care doesn't promote the involvement and the active participation of patients in their care. In conclusion we retain that the elements which influence the patients' behaviours with respect to their treatments do not only depend on training, but on their experiences and felts and also on their interactions with health professionals. The informative and educational care of the risk factors sometimes conceals the relational aspect of this therapeutic and the cognitive and emotive capacities of the patients. It should follow a double evolution: that of the patient (his emotions, his expectations, his life plans) and that of the pathology. This work also seeks to answer to the following question: why and how a socio- anthropological approach allows us to understand the patients' behaviours on one hand and the health professionals on the other hand in a context of PTE (patient's therapeutic education) in short stay? It argues for a reconnection between social sciences and medical and nursing in the French health care system and shows the significant contribution but still too little used by social sciences in this area.

In den ersten Versuchsreihen der hier vorliegenden Arbeit bestätigte sich, dass im in vitro Modell die klassische ischämische Präkonditionierung kardioprotektiv wirkt. Die Präkonditionierung bewirkte eine Infarktgrößenreduktion um 54 %; dies wird durch Literaturangaben bestätigt. Die Postkonditionierung dagegen, trotz drei verschiedener Postkonditionierungsprotokolle, ist am isoliert perfundierten Rattenherzen nicht protektiv. Im in vivo Rattenherz-Modell wurden die Präkonditionierung und die klinisch relevantere Postkonditionierung gegenüberstellend untersucht. Hier zeigte sich, dass die 3 Reperfusions-/Ischämiezyklen für jeweils 30 Sekunden der Postkonditionierung genauso protektiv wie die Präkonditionierung wirken. Infarktgrößen- und biochemische Untersuchungen belegen, dass hierbei die PI3-Kinase ein wichtiges Signaltransduktionselement ist, da einerseits durch die Inhibition der PI3-Kinase mittels Wortmannin die Infarktgrößenreduktion vollständig aufgehoben war und andererseits nach einer 1,5-minütigen Reperfusion eine vermehrte Phosphorylierung der Akt im Western-Blot auftrat. Des Weiteren konnte erstmals die Inaktivierung der GSK-3ß durch eine verstärkte Phosphorylierung über einen PI3-Kinase-vermittelten Signaltransduktionsweg nachgewiesen werden. Die Zugabe des spezifischen Inhibitors TDZD-8 der GSK-3ß verringert ebenfalls die Infarktgröße signifikant. Auch konnte zum ersten Mal gezeigt werden, dass das mammalian target of Rapamycin in der Postkonditionierung des in vivo Rattenherzens eine wichtige Rolle zu spielen scheint. Außerdem konnte neben dem PI3-Kinase/Akt-Signaltransduktionsweg auch die Beteiligung des MEK1/2-ERK1/2–Wegs als Signaltransduktionsweg der Postkonditionierung im in vivo Rattenherzen nachgewiesen werden. Erstmals wurde die Apoptose in einem in vivo Herzen nach regionaler Ischämie untersucht. Die Ergebnisse des TUNEL-Tests und der Western-Blot-Analysen zeigen eine unterdrückte Apoptose durch die Postkonditionierung. Ein weiterer Teil der vorliegenden Arbeit widmete sich der Untersuchung der Postkonditionierung in pathologischen Rattenherzen. Im Gegensatz zu gesunden Herzen schlug die Postkonditionierung in hypertrophiertem Myokardium von spontan-hypertensiven Ratten mit einer signifikant arteriellen Hypertension fehl. Diese Blockierung der Kardioprotektion zeigte sich durch die fehlende Reduzierung der Infarktgröße trotz unterschiedlicher Postkonditionierungsprotokolle (3x30’’ und 6x10’’ R/I) und unterschiedlich langer Ischämiedauern (20 und 30 Minuten). Gleichfalls war auch die Phosphorylierung der GSK-3ß aufgehoben. Als Modell des metabolischen Syndroms wurde die WOKW-Ratte untersucht. Diese Ratten entwickeln in sehr jungem Alter klassische Symptome wie Dyslipidämie, Hyperinsulinämie und Fettsucht. Wie bei der Herzhypertrophie war auch beim Modell des metabolischen Syndroms die Postkonditionierung - mit 3 Reperfusions-/ Ischämiezyklen für jeweils 30 Sekunden - blockiert. Dabei konnte weder eine Infarktgrößenreduktion noch eine vermehrte Phosphorylierung der GSK-3ß nachgewiesen werden. Die Ergebnisse der vorliegenden Arbeit erlauben die Schlußfolgerung, dass das Substrat der GSK-3ß, die mPTP des Mitochondriums, eine „Schlüsselrolle“ in der Apoptose innehat - die Postkonditionierung vermindert nicht nur die Nekrose, sondern reduziert auch die Apoptose. Bemerkenswert und potentiell von klinischer Bedeutung ist die Beobachtung, dass bei Vorliegen von Risikofaktoren, wie arterielle Hypertonie und metabolischem Syndrom, solche Schutzmechanismen des Herzens aufgehoben sind. Diese Erkenntnisse sind im Hinblick auf die Therapie am Menschen von großer Bedeutung. Ob langfristig einzelne Komponenten der Signaltransduktionswege, wie PI3-Kinase, Akt, mTOR, ERK1/2 oder GSK-3ß, Angriffspunkte einer pharmakologischen Therapie sein könnten, muß in weiteren Untersuchungen geklärt werden.

No description available.

Background: Treatment of cardiovascular risk factors slows the progression of small abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a stress- and hemin-induced enzyme providing cytoprotection against oxidative stress when overexpressed. However, nothing is known about the effects of cardiometabolic standard therapies on HO-1 expression in aortic walls in patients with end-stage AAA. Methods: The effects of statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), betablockers, diuretics, acetylsalicylic acid (ASA), and therapeutic anticoagulation on HO-1 mRNA and protein expressions were analyzed in AAA patients using multivariate logistic regression analysis and comparison of monotherapy. Results: Analysis of monotherapy revealed that HO-1 mRNA and protein expressions were higher in patients on diuretics and lower in patients on statin therapy. Tests on combinations of antihypertensive medications demonstrated that ACE inhibitors and diuretics, ARBs and diuretics, and beta-blockers and diuretics were associated with increase in HO-1 mRNA expression. ASA and therapeutic anticoagulation were not linked to HO-1 expression. Conclusion: Diuretics showed the strongest association with HO-1 expression, persisting even in combination with other antihypertensive medications. Hence, changes in aortic HO-1 expression in response to different medical therapies and their effects on vessel wall degeneration should be analyzed in future studies.

La dysfonction endothéliale vasculaire constitue un marqueur précoce des maladies cardiovasculaires car l’endothélium est l’une des premières cibles des facteurs de risque cardiovasculaire. La présence d'un stress chronique engendré par les facteurs de risque cardiovasculaire sollicite les mécanismes de défense endogènes, tels que les enzymes antioxydantes, qui servent au maintien de la fonction endothéliale. L’environnement vasculaire auquel l’endothélium est exposé a un effet direct sur son fonctionnement à long terme. Certaines habitudes de vie sont ainsi associées à une bonne santé cardiovasculaire. Par exemple, la diète méditerranéenne et/ou la pratique régulière de l’exercice physique aident à maintenir une fonction endothéliale adéquate et à réduire l’incidence des maladies cardiovasculaires. D'autre part, certains gènes clés, comme le gène suppresseur de tumeurs p53, régulent plusieurs voies métaboliques importantes pour préserver l’intégrité des cellules endothéliales. Nous posons l’hypothèse que l’environnement vasculaire post-natal influence la mise en place de mécanismes de défenses endogènes tels que les enzymes antioxydantes afin de faire face à des stress plus tard dans la vie. Notre objectif global était d’évaluer les impacts d’interventions post-natales bénéfiques et d’une diminution endogène du gène suppresseur de tumeurs p53, sur la fonction endothéliale vasculaire et sur sa capacité à faire face à un stress métabolique. Dans une première étude, nous avons soumis des souris saines C57Bl/6 dès leur sevrage et jusqu’à l’âge de 9 mois, à un programme d’exercice physique volontaire (course dans une roue) ou à un antioxydant (catéchine), comparé à un groupe de souris sédentaires et sans antioxydant. Puis les interventions ont été stoppées et une diète riche en gras a été introduite, ou non, pour une période de 3 mois; les souris ont été sacrifiées à l'âge de 9 ou 12 mois. Nous avons observé que l’exercice a protégé les cellules endothéliales des effets délétères induits par la diète riche en gras en préservant la fonction endothéliale par le maintien d’un profil rédox sain et en évitant la hausse de l’inflammation. La catéchine a maintenu la fonction endothéliale aortique, mais n’a pas prévenu le profil inflammatoire en présence de la diète riche en gras. Finalement, chez les souris sédentaires, la fonction endothéliale a été détériorée en présence de la diète riche en gras, sans indice d’inflammation vasculaire. Dans une seconde étude, des souris partiellement déficientes en p53 (p53+/-) et contrôles C57Bl/6 ont été exposées à la même diète riche en gras à partir de 3 mois et ce jusqu’à l’âge de 6 mois. Notre raisonnement était basé sur la démonstration que p53 est un régulateur de l’expression des enzymes antioxydantes in vitro. Chez les souris p53+/-, les cellules endothéliales ont été protégées du stress induit par l’hypercholestérolémie engendrée par la diète riche en gras. Cependant, chez les souris p53+/- cette protection pourrait être secondaire à un métabolisme accru des acides biliaires, qui en prévenant la hausse de cholestérol, protègerait indirectement l'endothélium. Nous avons donc pu démontrer l’importance de l’environnement vasculaire sur la fonction endothéliale. La diète riche en gras a stimulé certains mécanismes de défense vasculaires tels que la voie des EDHF et la superoxyde dismutase afin de maintenir la fonction endothéliale malgré les conditions pro-athérosclérotiques. Nous avons observé que l’exercice et la catéchine influencent différemment l’endothélium malgré leurs capacités antioxydantes. Ces études soulignent la sensibilité de l’endothélium aux changements dans l’environnement vasculaire. En accord avec le vieillissement de la population et la progression des maladies cardiovasculaires, la proportion de personnes ayant une dysfonction endothéliale augmente. Ainsi, une meilleure compréhension des mécanismes ou d’interventions qui permettent le maintien de la fonction endothéliale à long terme s’avère utile. / Endothelial dysfunction is an early marker of atherosclerosis and cardiovascular diseases. Cardiovascular risk factors generate a chronic stress, challenging endogenous defense mechanisms that are critical to maintain endothelial function, such as antioxidant enzymes. The vascular environment impacts the integrity and long-term function of endothelial cells. Thus, a healthy lifestyle is beneficial for cardiovascular health: regular physical training and/or a Mediterranean diet are associated with the maintenance of endothelial function and a lower incidence of cardiovascular diseases. On the other hand, some key genes such as tumor suppressor gene p53, are known to regulate numerous cellular functions that are necessary to maintain endothelial cells integrity. We hypothesized that the post-natal vascular environment impacts the development of endogenous cellular defense mechanisms such as antioxidant enzymes, in order to protect against vascular stress that will occur later in life. Our major goal was to evaluate the impact of post-natal interventions and endogenous reduction of p53 expression on vascular endothelial function and its capacity to resist against a metabolic stress. In our first study, healthy C57Bl/6 mice were exposed from weaning to the age of 9 months to physical voluntary training (running wheel) or to the antioxidant catechin, and were compared to physically inactive mice that did not receive catechin. Then, exercise and catechin were stopped and mice were subjected to a regular or a high fat diet for 3 months; mice were sacrificed either at the age of 9 or 12 months. In trained mice, we observed that exercise prevented endothelial dysfunction and inflammation induced by the high fat diet. In catechin-treated mice, aortic endothelial function was maintained despite exposure to the high fat diet, but an inflammatory profile was observed. In physically inactive mice, the high fat diet induced endothelial dysfunction without inflammation. In our second study, mice partially deficient in p53 (p53+/-) were exposed to the same high fat diet from 3 to 6 months of age. Our rationale was based on the discovery that in vitro, p53 regulates antioxidant enzymes gene expression. In p53+/- mice, endothelial cells were protected from the stress of hypercholesterolemia induced by the high fat diet. However, this endothelial protection could be linked with an unexpected enhanced bile acid metabolism in p53+/- mice: low endogenous expression of p53 prevents the rise in plasma total cholesterol when fed a high fat diet, indirectly protecting the endothelium. In summary, we were able to demonstrate the importance of the vascular environment on endothelial function. The pro-atherosclerotic environment induced by the high fat diet stimulated vascular defense mechanisms, as observed by the activation of the compensatory EDHF pathway and superoxide dismutase activity, to maintain an adequate endothelial function. We observed that exercise and catechin had a different impact on the endothelium despite their antioxidant properties. These studies demonstrate the sensitivity of the endothelium to changes within the vascular environment. As the population is aging and the incidence of cardiovascular diseases is increasing, endothelial dysfunction will be more frequent. Therefore, a better comprehension of mechanisms or interventions that can protect endothelial function can only be beneficial.

Contexte L’américanisation des habitudes de vie, notamment de l’alimentation, semble être en grande partie responsable de l’augmentation incessante de l’incidence élevée des maladies cardiovasculaires. La période postprandiale, où l’homéostasie vasculaire et métabolique est mise à l’épreuve, est d’une importance considérable dans le développement ou la prévention de l’athérosclérose et représente maintenant la majeure partie du temps d’éveil. La compréhension de l’influence de la composition d’un repas sur son impact postprandial est donc essentielle dans notre lutte dans la prévention de ces maladies. Objectifs L’objectif principal de ce projet de recherche était d’étudier les réponses endothéliale et métabolique à un repas de type méditerranéen mixte (MMM), puisqu’elles sont inconnues. Ce projet avait aussi pour objectifs d’évaluer l’impact microvasculaire d’un tel repas et de caractériser la composition postprandiale des acides gras plasmatiques. À titre comparatif, ces éléments ont aussi été étudiés suite à un repas riche en gras saturés (HSFAM). Méthodes Vingt-huit (28) hommes sains, exempts de facteurs de risque de maladies cardiovasculaires ont reçu de façon randomisée les deux repas à l’étude. Le MMM, composé de saumon frais et de légumes cuits dans l'huile d'olive, contenait 7.87g de SFA et 2.29g d’acides gras polyinsaturés oméga-3, tandis que le HSFAM, composé d'un sandwich déjeuner avec œuf, saucisse et fromage, contenait 14.78g de SFA. Les mesures de la fonction endothéliale mesurée par échographie brachiale (FMD), de la fonction microvasculaire mesurée par spectroscopie proche de l’infrarouge (NIRS) et de la composition des acides gras plasmatique ont été effectuées à jeun et en période postprandiale. Résultats Deux sous-groupes de répondeurs aux repas à l’étude se sont dégagés de ces travaux. Un premier sous-groupe de sujets ayant une triglycéridémie à jeun élevée, mais normale (hnTG) a démontré des altérations endothéliales seulement suivant le repas HSFAM. Un second sous-groupe de sujets ayant une triglycéridémie plus faible et normale (lnTG) n’a quant à lui pas subi d’altérations endothéliales suivant les deux repas à l’étude. Les sujets hnTG ont aussi démontré une charge triglycéridémique postprandiale (iAUC) plus importante et qui était de surcroît enrichie en acide stéarique suivant la HSFAM et en acide gras polyinsaturés oméga-3 suivant le MMM. L’évaluation par NIRS de la fonction microvasculaire nous révèle un ralentissement de la réoxygénation post-ischémique qui suggère une altération postprandiale du recrutement capillaire chez les sujets hnTG seulement. De telles altérations, qui semblent être plus importantes suivant le HSFAM, pourraient être en partie responsables de l’impact endothélial de ce repas. Conclusions Cet essai clinique démontre donc de façon novatrice qu’un repas MMM n’a pas d’effet endothélial délétère et que cette neutralité est indépendante de la triglycéridémie à jeun. De plus, une triglycéridémie à jeun élevée mais normale semble indiquer des dysfonctions endothéliales et métaboliques à des épreuves nutritionnelles tel un repas HSFAM. La consommation de repas méditerranéens par des individus sains à la triglycéridémie marginale serait bénéfique, peut-être même davantage que pour des individus de triglycéridémie plus faible, dans la prévention de l’athérogénèse et des maladies cardiovasculaires. / Background The Westernization of lifestyles, notably dietary habits, seems to be largely responsible for the ongoing increase of incidence of cardiovascular diseases. The postprandial period, where vascular and metabolic homeostatic regulating processes are under pressure, is of considerable importance in the development or prevention of atherosclerosis and now represents the majority of waking hours. The understanding of the postprandial effects of meals of varying composition is therefore essential in our effort to prevent such diseases. Objectives The main objective of this research project was to study the endothelial and metabolic responses to a mixed Mediterranean meal (MMM), since they are unknown. This project also aimed to evaluate the microvascular impact of such a meal and to characterize the composition of postprandial plasma fatty acids. These elements were also evaluated following a saturated fatty meal (HSFAM) for comparison. Methods Twenty-eight (28) healthy men free of cardiovascular diseases and risk factors were randomly assigned one of two test meals. The MMM, consisting of fresh salmon and vegetables cooked in olive oil, contained 7.87g of SFA and 2.29g of omega- 3 fatty acids, while the HSFAM, consisting of a breakfast sandwich with egg, sausage and cheese contained 14.78g of SFA. Evaluations of endothelial function by brachial ultrasound (FMD), of microvascular function by near-infrared spectroscopy (NIRS) and of plasma fatty acids composition were done in the fasted and postprandial states. Results Two subgroups of responders to the test meals emerged from this work. A first subgroup of subjects with high-normal fasting triglyceridemia (hnTG) experienced impairments of endothelial function following the HSFAM while a second subgroup of subjects with low-normal triglyceridemia (lnTG) did not experience any endothelial alterations following this meal. Interestingly, the MMM had no deleterious endothelial impact in any of those subgroups. Moreover, the hnTG subjects demonstrated greater postprandial triglyceridemic load (iAUC) that was in addition enriched with stearic acid after HSFAM and omega-3 PUFA following the MMM. Assessment of microvascular function revealed postprandial prolongation of post-ischemic reoxygenation only in hnTG subjects suggestive of alterations of capillary recruitment. These changes, which seemed to be more important after the HSFAM, could be partly responsible for its negative impact on FMD. Conclusions This clinical trial demonstrates in innovative ways that a MMM has no deleterious effects on endothelial function irrespective of triglyceridemia in normal ranges. In addition, high but normal fasting triglyceride levels suggest metabolic and endothelial dysfunctions following nutritional challenges such as a HSFAM. Consumption of Mediterranean meals by healthy individuals with marginal triglyceride levels would be beneficial, perhaps even more so than for individuals with lower triglyceride levels, in preventing atherogenesis and cardiovascular diseases.