Introdução: A psoríase é uma doença sistêmica crônica, inflamatória e imuno- mediada, que afeta a pele, vasos e sistema osteomuscular. A inflamação é um fator de risco importante para a aterosclerose, e a psoríase está associada com risco aumentado de dislipidemia, diabetes, hipertensão, obesidade e esteato-hepatite não alcoólica. No entanto, o impacto da inflamação crônica sistêmica sobre a saúde vascular e aterosclerose permanece mal compreendido. Objetivos: Analisar a associação entre psoríase e aterosclerose subclínica com uma medição não invasiva, avaliada no ramo das artérias carótidas, usando a espessura médio-intimal (IMTc). O objetivo secundário foi comparar a IMTc entre os subgrupos psoríase: leve, moderada à psoríase/grave e artropática, com o grupo controle. Métodos: Neste estudo caso-controle transversal, 221 pacientes com psoríase (31,2% psoríase leve, 41,6% psoríase moderada/grave e 31,2% psoríase artropática) foram comparados com um grupo de 5.061 controles existentes recrutados a partir de um inquérito anterior (ELSA-Brasil HU-USP). Os critérios de inclusão compreendem os seguintes fatores: acima de 40 anos de idade para mulheres e 35 anos para homens; psoríase diagnosticada e clinicamente ativa, pelo menos há dois anos. Os critérios de exclusão foram: gravidez, presença de neoplasia, gota, artrite reumatóide e lúpus eritematoso sistêmico. Todos os participantes foram submetidos a exame médico, exame clínico e dados antropométricos recolhidos, bem como amostras de sangue para análise laboratorial. Em seguida, foram realizados exame de ultrassonografia das artérias carótidas direita e esquerda a fim de determinar IMTc. Ambos os lados analisados com média dos valores; quando aumentados foram utilizadas como um indicador da aterosclerose subclínica. Resultados: No grupo psoríase, o tempo médio de doença foi de 16 (± 13) anos. Em relação ao IMT da carótida (média dos lados direito e esquerdo), não observamos valores aumentados no grupo de psoríase, em comparação com o grupo controle, com os dados crus (P = 0,24 e P = 0,83, IMT esquerda e IMT direita, respectivamente). No entanto, quando o ajuste por sexo e idade (P = 0,038 e P < 0,0001, IMT para a esquerda e direita, respectivamente) e um ajuste multivariado para o risco cardiovascular, uma diferença significativa é encontrada (P = 0,028 e P < 0,0001, IMT esquerda e IMT direita, respectivamente) com valores mais elevados da carótida IMT no grupo de psoríase do que no grupo controle. Em consonância com isso, não foram observadas diferenças na IMT entre ameno, sub-grupos artrite psoriática moderado-grave e grupo controle (P = 0,50 e P = 0,52, respectivamente). Hipertensão, Hs CRP, IMC, HDL e LDL foram maiores nos pacientes com psoríase, em comparação com os controles (ambos p < 0,001). Conclusões: Na coorte brasileira, pacientes com psoríase apresentaram um perfil mais grave de fatores de risco cardiovascular do que os controles, em função do aumento da espessura da parede da artéria carótida encontrada nesses pacientes. O papel preciso da inflamação sistêmica crônica e outros fatores sobre a progressão da doença e comorbidades devem ainda ser elucidados . / Introduction: Psoriasis is a chronic systemic immune-mediated inflammatory disease affecting skin, vessels and osteomuscular system. Inflammation is an important risk-factor for atherosclerosis and psoriasis is associated with increased risk for dislipidemia, diabetes, hypertension, obesity and non-alcoholic steatohepatitis. However, the impact of chronic systemic inflammation on vascular health and atherosclerosis remains poorly understood. Objectives: To examine the association between psoriasis and subclinical atherosclerosis assessed at the carotid artery branch using a non-invasive measurement of the intima-media thickness (IMTc). The secondary objective was to compare the IMTc between psoriasis subgroups: mild, moderate / severe psoriasis and arthropathica with control group. Methods: In this cross-sectional case-control study, 221 psoriasis patients (31.2% mild psoriasis, 41.6% moderate-severe psoriasis and 31.2% arthritic psoriasis) were compared with a group of 5,061 existing controls recruited from a previous investigation (ELSA-Brasil HU-USP). Inclusion criteria were: 40 y of age for women and 35 y of age for men; psoriasis diagnosed and clinically active for at least 2 years. Exclusion criteria were: pregnancy, neoplasia, gout, rheumatic arthritis and systemic lupus erythematosus. All participants were submitted to medical screening, clinical examination and had anthropometric data collected as well as blood samples for laboratorial analysis. Then, they undertook an ultrasound scan of the right and left carotid arteries in order to determine IMTc. Both sides were averaged and increased values were used as an indicator of subclinical atherosclerosis. Results: The psoriasis group the mean disease time was 16±13 years. In relation to the carotid IMT (right and left sides averaged), we did not observe increased values in the psoriasis group as compared to the control group, with crude data (P = 0,24 and P = 0,83, IMT left and IMT right respectively). However, when adjusting by sex, age (P = 0,038 and P < 0,0001, IMT left and IMT right respectively) and a multivariate adjustment for cardiovascular risk, a significant difference is found (P = 0,028 and P < 0.0001, IMT left and IMT right respectively) with higher carotid IMT values in the psoriasis group than in the control group. In line with this, no differences were observed in the IMT between mild, moderate-severe, psoriatic arthritis sub-groups and control group (P = 0.50 e P = 0.52, respectively). Hypertension, Hs CRP, BMI, HDL and LDL were higher in psoriasis patients as compared to controls (both p < 0.001). Conclusions: In the Brazilian cohort, psoriasis patients presented a more severe profile of cardiovascular risk factors than controls, with increased carotid arterial wall thickness being found in these patients. The precise role of chronic systemic inflammation and other factors on disease progression and comorbidities are yet to be elucidated

Les populations sont exposées quotidiennement à mélange complexe de polluants de l’air, comme les particules fines, le dioxyde de soufre et le dioxyde d’azote, qui ont été associés à de nombreux effets de santé, notamment d’ordre respiratoire et cardiovasculaire. La répartition des sources émettrices, les caractéristiques du paysage (c.-à-d. le cadre bâti, la topographie) et par conséquent ce mélange et l’exposition des populations varient de manière spatio-temporelle. L’objectif de ce mémoire était de documenter les inégalités sociales d’exposition aux émissions industrielles de polluants de l’air et les effets cardiovasculaires aigus de l’exposition journalière à ces polluants chez des populations vulnérables résidant à proximité de ces sources. Ainsi, à l’aide d’une étude écologique, nous avons analysé les corrélations entre le niveau de défavorisation (quatre indicateurs) de 2189 écoles primaires et secondaires québécoises et leur exposition aux émissions industrielles dans des rayons de 2,5 à 7,5 km. Nos résultats suggèrent des inégalités d’exposition des populations infantiles aux émissions industrielles à l’école, cependant elles n’étaient pas constantes pour les quatre indicateurs. En outre, nous avons analysé, utilisant une étude cas-croisés, le lien entre l’exposition aux polluants industriels estimés à l’aide des émissions et des concentrations de ces polluants, et les décès pour maladies cardiovasculaires chez des personnes âgées résidant dans un rayon de 7,5 km d’une industrie. Aucune association convaincante n’a été notée ; nos résultats étaient très variables ; cela était probablement dû aux limites associées à l’estimation de l’exposition de notre étude. De futures études avec de meilleures estimations d’exposition seront nécessaires pour soutenir ces résultats. / On a daily basis, populations are exposed to a complex mixture of air pollutants such as fine particulate matters, sulphur dioxide and nitrogen dioxide that have been associated with a range of health effects namely respiratory and cardiovascular effects. Emitting sources’ distribution, landscape characteristics (i.e. infrastructure, topography) and thus the complex mixture of air pollutants and populations’ exposure vary greatly in space and time. This thesis aimed to document social inequalities in exposure to industrial air emissions of pollutants and associations between daily exposure to these pollutants and cardiovascular mortality in vulnerable populations living near these sources. Thus, using an ecological design, we analyzed Pearson’s correlations between deprivation level (using four indicators) of 2,189 primary and secondary Quebec schools and their exposure to industrial emissions in a radius of 2.5 to 7.5 km. Our results suggest inequalities in exposure to industrial air emissions at school in children. These associations were not consistent among all four indicators of deprivation. Besides, using a case-crossover design, we evaluated the associations between exposure to industrial air pollutants using both emission exposure estimates and sensor levels and deaths from cardiovascular diseases in the elderly living near industrial sources (<7.5 km). We found no convincing evidence of association. Our results varied greatly which could be caused by the limits of our study related to estimating exposure. Further studies using improved exposure estimates are necessary to support our findings.

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. The main features of the syndrome include menstrual irregularities and hyperandrogenism. In addition to symptoms related to fertility, some women also suffer from an unfavourable metabolic profile including impaired glucose tolerance, dyslipidaemia and low-grade chronic inflammation. In the present studies we aimed to investigate the role of age on adrenal and ovarian androgen secretion in 79 women with PCOS and 98 healthy women, with special focus on the menopause. Furthermore, we studied the effects of combined hormonal contraceptives (CHCs) administered orally, transdermally and vaginally (n=42, healthy women, 9 weeks) and atorvastatin treatment (n=28, women with PCOS, 6 months) on androgen levels and metabolic factors. Androgen secretion capacity was analysed by using adrenal and ovarian stimulation tests and glucose tolerance by using oral and intravenous glucose tolerance tests. Furthermore, chronic inflammation was assessed via assay of C-reactive protein and pentraxin-3. Basal and stimulated adrenal and ovarian androgen production was elevated and levels remained higher in women with PCOS compared with healthy women even after the menopause. Furthermore, women with PCOS presented with enhanced insulin resistance and chronic inflammation, which persisted beyond menopausal transition. During CHC treatment, the route of administration was insignificant, and all treatments impaired insulin sensitivity and increased chronic inflammation. In women with PCOS, treatment with atorvastatin improved chronic inflammation and the lipid profile as expected, but worsened glucose tolerance and did not affect testosterone levels. Regardless of strict exclusion criteria, where only relatively healthy women with PCOS were recruited, the results showed that enhanced androgen secretion and unfavourable metabolic alterations associated with PCOS persist through menopausal transition. The findings emphasize the importance of monitoring glucose metabolism during the use of CHCs, especially in women with known risks of type 2 diabetes. Atorvastatin treatment exacerbates insulin resistance in women with PCOS and therefore the treatment should only be considered after individual risk assessment of cardiovascular disease and not just because of PCOS. / Tiivistelmä Monirakkulainen munasarjaoireyhtymä (PCOS) on hedelmällisessä iässä olevien naisten yleisin hormonaalinen ongelma. Tyypillisiä PCOS:n oireita ovat munarakkuloiden epäsäännöllisestä kypsymisestä johtuvat kuukautiskierron häiriöt ja miessukuhormonien eli androgeenien liikatuotanto. Hedelmällisyyttä heikentävien oireiden lisäksi PCOS:än liittyy aineenvaihdunnan ongelmia, kuten heikentynyttä sokerinsietoa sekä taipumus rasva-aineenvaihdunnan häiriöihin ja krooniseen tulehdukseen. Tutkimuksessa selvitettiin ikääntymisen ja vaihdevuosien vaikutuksia lisämunuais- ja munasarjaperäiseen androgeenieritykseen 79 PCOS-naisella ja 98 terveellä naisella. Lisäksi tutkittiin eri yhdistelmäehkäisyvalmisteiden antoreittien (suu, iho, emätin) (n=42, terveet naiset, 9 viikkoa) ja atorvastatiinihoidon (n=28, PCOS-naiset, 6 kuukautta) vaikutuksia androgeenitasoihin ja aineenvaihdunnallisiin muuttujiin. Androgeenieritystä tutkittiin lisämunuaisten ja munasarjojen stimulaatiotesteillä ja sokeriaineenvaihdunnan muutoksia suun kautta ja suonensisäisesti tehtävillä sokerirasituskokeilla. Tulehduksellista tilaa mitattiin määrittämällä C-reaktiivisen proteiinin ja pentraksiini-3:n pitoisuuksia. Lisämunuaisten ja munasarjojen androgeenieritys oli PCOS-naisilla lisääntynyt terveisiin naisiin verrattuna, ja ero säilyi vaihdevuosi-iän jälkeen. PCOS-naisilla esiintyi myös enemmän heikentynyttä sokerinsietoa ja kroonista tulehdusta vielä vaihdevuosi-iän jälkeenkin. Hormonaalinen yhdistelmäehkäisy heikensi insuliiniherkkyyttä sekä pahensi pitkäaikaista tulehdusta annostelureitistä riippumatta. Atorvastatiinihoito puolestaan paransi pitkäaikaista tulehdusta sekä rasva-aineenvaihduntaa PCOS-naisilla, mutta huononsi sokerinsietoa ja insuliiniherkkyyttä eikä sillä ollut vaikutusta testosteronitasoihin. Koska poissulkukriteerit olivat tiukat, tutkimuksiin valikoitui varsin terveitä PCOS-naisia. Siitä huolimatta osoittautui, että PCOS:än liittyvä lisääntynyt androgeenituotanto sekä epäedulliset aineenvaihdunnan muutokset jatkuvat vielä vaihdevuosi-iän jälkeen. Hormonaalisen yhdistelmäehkäisyn käytön aikana olisi hyvä seurata sokeriaineenvaihdunnan muutoksia erityisesti niillä naisilla, joilla on kohonnut riski sairastua aikuistyypin diabetekseen. Atorvastatiinihoito huonontaa PCOS-naisilla insuliiniherkkyyttä, minkä vuoksi hoito tulisi aloittaa vain yksilöllisen riskiarvion perusteella.

Dados epidemiológicos documentaram a associação entre elevação moderada dos níveis da proteína C-reativa (PCR) pela técnica hipersensível (PCRhs), dentro da variação normal, e risco cardiovascular em indivíduos sem doença clínica vascular. A potencial aplicação da PCRhs, como uma ferramenta auxiliar na avaliação global, de risco requer conhecimento de sua distribuição na população e das características clínicas envolvidas. Há carência de dados sobre a influência sobre a genética na concentração da PCR. Formulamos a hipótese de que variações alélicas (polimorfismo) no gene que codifica a PCR poderiam interferir na sua concentração sérica. Avaliamos a distribuição da concentração sérica da proteína C-reativa determinada pela técnica hipersensível em indivíduos de uma população brasileira sem evidências clínica e laboratorial de cardiopatia, e as variações desta concentração e, relação às características clínicas, variáveis laboratoriais e ao polimorfismo G1059C do gene da PCR. Realizamos um estudo de coorte, de indivíduos assintomáticos com exames clínico e cardiológico normais, atendidos na Unidade Clínica de Ambulatório Geral do Instituto do Coração (InCor) do Hospital das Clínicas da Universidade de São Paulo, no período de julho de 1998 a julho de 2001. Critérios de inclusão: indivíduos assintomáticos com exame físico normal, eletrocardiograma de repouso e esforço normais e radiografia do tórax normal. Foram excluídos aqueles com glicemia superior a 125 md/dl, alterações na concentração sérica do hormônio tíreo-estimulante (TSH) e sorologia positiva para doença de Chagas. Foram elegíveis 684 indivíduos: 295 (43,1%) do sexo masculino e 389 (56,9%) do feminino. Suas idades variaram entre 14 e 74 anos (média 40,6; desvio-padrão 11,5); 513 (75,0%) eram brancos, 117 (17,1%) mulatos, 32 (4,7%) amarelos e 22 (3,2%) negros. O tabagismo foi relatado por 160 (23,4%) indivíduos e 524 (76,6%) não eram tabagistas. A avaliação laboratorial incluiu a dosagem de glicemia, colesterol total e frações, triglicérides e ácido úrico. Foram colhidas amostras de sangue para dosagem sérica da PCRhs e genotipagem de PCR. A ecocardiografia bidimencional com Doppler foi realizada em 634 indivíduos, com resultado normal. A concentração sérica da PCRhs foi distribuída por quartis da população em estudo, os valores mínimo e máximo por quartil foram: 1º quartil 0,014-0,037 mg/dl; 2º quartil 0,0384,07 mg/dl; 3º quartil 0,080-0,187 mg/dl e 4º quartil 0,188-1,31 mg/dl. Num modelo de regressão múltipla as variáveis independentes correlacionadas ao log da PCRhs foram: idade (p=0,03), índice de massa corpórea (IMC) (p<0,01), razão colesterol total/HDL colesterol (ColT/HDL-C) (P<0,01) e frequência cardíaca (p<0,01). Para avaliar o comportamento das variáveis significativas deste modelo de regressão, a amostra foi estratificada em quatro grupos, segundo sexo e tabagismo, e foram estimados quatro modelos múltiplos. Nos homens tabagistas foram variáveis significativas a idade (p=0,04) e a razão ColT/HDL-C (p<0,01); nos homens não tabagistas foram o IMC (p<0,01) e a razão ColT/HDL-C (p<0,01); nas mulheres tabagistas o IMC (p<0,01) e nas mulheres não tabagistas foram o IMC (p<0,01), a razão ColT/HDL-C (p=0,01) e a frequência cardíaca (p=0,02). Não houve diferença estatisticamente significativa (p<0,05) na concentração da PCRhs entre os diferentes genótipos do gene da PCR. Portanto as variáveis idade, IMC, razão ColT/HD1-C e frequência cardíaca, não se relacionam com a concentração sérica da PCRhs de maneira homogênea, mas sim de acordo com o subgrupo analisado, referente ao sexo e tabagismo; e as concentrações da PCRhs não diferiram quanto a presença ou ausência do polimorfismo G1059C do gene da PCR. / Epidemiologic data have documented the association between moderate elevation, within the normal range, of the C-reactive protein (CPR) serum levels measured by high-sensitivity assays (hs-CRP), and cardiovascular risk among individuals without clinical evidence of vascular disease. The potential use of hs-CRP as a new auxiliary tool in the assessment of overall risk requires that its distribution in the population and the related clinical characteristics are known. There is few data about the influence of genetics upon CRP concentration. The hypothesis that allele variations in the gene responsible for coding CRP (polymorphism) could interfere with CRP serum concentration has been posed. The aim of this study was to assess the distribution of C-reactive protein (CRP) serum concentration measured by high-sensitivity assay (hs-CRP), in a Brazilian population of individuals without heart disease, as well as the association of variations of that concentration with clinical characteristics and laboratory variables, and with the CRP gene G1059C polymorphism. A cohort of asymptomatic patients visiting the Outpatient Clinic of the Heart Institute (InCor) of the University of São Paulo Medical School between July 1998 and July 2001, all with normal results in the clinical and cardiological evaluations, was studied. The inclusion criteria were: asymptomatic individuals with normal results in the physical evaluation, normal electrocardiography and stress test, and normal chest X-ray examination. Individuals with glucose level above 125mg/dl, changes in the thyroid-stimulating hormone (TSH) serum concentration, and positive serology for Chagas\' disease, were excluded. Thus, 684 individuals, 295 men (43.1 %) and 389 women (56.9%), ages 14 to 74 (mean 40.6, SD 11.5) years, were eligible. White people in the cohort were 513 (75.0%), mulatto 117 (17.1%), eastern people 32 (4.7%) and 22 of black color (3.2%) 160 individuals (23.4%) reported as currently smoking, while 524 (76.6%) were non-smokers Laboratory screening consisted of dosing of glucose, total and partial: cholesterol, triglycerides and uric acid plasma levels. Doppler two-dimensional echocardiography was performed in 636 individuals, all with normal results. Serum hs-CRP concentration of the study population was distributed in quartiles, with minimum and maximum values per quartile as follows: 1st quartil, 0.014-0.037mg/dl; 2nd quartile: 0.038-0.078mg/dl; 3rd quartile 0.080-0.\'187mg/dl; and 4th quartile: 0.188-1,31mg/dl. Multiple regression analysis has shown that the independent variables correlating with hs-CRP-log were age (p=0.03), body mass index (p<0.01), total/HOL cholesterol ratio (p<0.01) and heart rate (p<0.01). The study population was stratified in 4 groups according to gender and smoking status, to verify the behavior of the significant variables in this regression model, with estimation of 4 multiple models. Significant variables were: among currently smoking men, age (p=0.04) and Total/HDL cholesterol ratio (p<0.01); among non-smoking men, BMI (p<0.01) and Total/HDL cholesterol ratio (p<0.01). Among currently smoking women, only BMI (p<0.01) was significant, and among non-smoking women, BMI (p<0.01), Total/HDL cholesterol ratio (p=001) and heart rate (p=0.02) were significant. There was no statistically significant difference (p<005) of the hs-CRP serum concentration in the groups with GG genotypes or the CRP gene G1059C polymorphism. Our findings led to the conclusion that the variables age, BMI, Total/HDL cholesterol: ratio and heart rate do not correlate homogeneously with the hs-CRP serum concentration in this study population, but according to the specific gender or smoking status subgroup being studied this is verified. Additionally, hs-CRP concentrations did not differ according to the presence or the absence of the CRP gene G1059C polymorphism.

O infarto do miocárdio (IM) é a doença cardiovascular que mais causa morte e invalidez em todo o mundo. O uso de animais experimentais tem auxiliado a compreender melhor a fisiopatologia e as formas de tratamento do IM. Sabendo que as dislipidemias estão associadas com o IM e que o treinamento físico pode ser prescrito para prevenção e tratamento de doenças cardiovasculares, no presente trabalho, investigamos os efeitos de dois tipos de treinamentos físicos em um modelo experimental de dislipidemia e isquemia miocárdica. Camundongos selvagens (WT) e knockout para o receptor LDL (LDL-/-) foram divididos em oito grupos: a) LDLr-/- sedentário (LDL-S); b) LDLr-/- infartado sedentário (LDL-IM-S); c) LDLr-/- infartado submetido a treinamento contínuo (LDL-IM-C); d) LDLr-/- infartado submetido a treinamento intervalado (LDL-IM-I); e) WT sedentário (WT-S); f) WT infartado sedentário (WT-IM-S); g) WT infartado submetido a treinamento contínuo (WT-IM-C); h) WT infartado submetido a treinamento intervalado (WT-IM-I). Após 60 dias da ligadura da artéria coronária descendente, o treino contínuo constou de corrida a 60% do máximo e o intervalado de 8 tiros de 4min a 80% do máximo e recuperação de 4min a 40% do máximo. Nos animais WT infartados, ambos os treinamentos aumentaram a tolerância ao esforço e provocaram diminuição do balanço simpatovagal e aumento do índice alfa em magnitudes semelhantes. O treinamento intervalado reduziu o número de fibras do tipo II em relação aos grupos WT-S e WT-IM-C, bem como reduziu a quantidade de fibras do tipo II-X em relação aos WT-S. A área de secção transversa das fibras do tipo I foi maior no grupo WT-IM-I do que no WT-IM-S e WT-S. A razão capilar/fibra foi maior nos animais do grupo WT-I do que no WT-S. A fração de ejeção e a fração de encurtamento foi menor no grupo LDL-IM-I em relação aos demais, mas sem diferenças entre os grupos WT-S, WT-IM-C e WT-IM-I. Nos animais LDL-/-, o LDL foi maior e o VLDL menor no grupo LDL-IM-C em relação aos demais. O HDLtg(%) foi superior no LDL-C em relação ao LDL-S. O HDLc (mg e %) do LDL-IM-I foi maior que o do grupo LDL-IM-C, sendo que o HDLc (mg) do LDL-IM-I foi, ainda maior do que o grupo LDL-S. O triglicérides total foi menor no grupo LDL-IM-C do que no LDL-S. Somente o grupo LDL-IM-I diminuiu a FC de repouso em relação ao grupo LDL-IM-S. A PA diastólica foi menor no grupo LDL-IM-S em relação ao LDL-S, enquanto que o grupo LDL-IM-I apresentou PA diastólica maior do que o grupo LDL-IM-C. A variância do intervalo de pulso foi maior no grupo LDL-S somente em relação ao grupo LDL-IM-I. Em conjunto nossos resultados demonstraram que os animais LDL possuem diferenças funcionais e fisiológicas importantes em relação ao WT, especialmente na morfologia muscular, na hemodinâmica e no controle autonômico. Que o IM acarretou prejuízos em ambas as linhagens investigadas e que os dois tipos de TF atenuaram semelhantemente esses prejuízos em grande parte das variáveis analisadas / Myocardial infarction (MI) is a major cause of death and disability worldwide. The use of experimental animals has supported to better understand the pathophysiology and treatment forms of myocardial infarction (MI). Knowing that the dyslipidemia associated with IM and that physical training can be prescribed for prevention and treatment of cardiovascular diseases, the present study investigated the effects of two types of physical training on an experimental model of dyslipidemia and myocardial ischemia. Wild mice (WT) and LDL receptor knockout (LDL-/- ) were divided into eight groups: a) LDLr-/- sedentary (LDL-S), b) LDLr-/- myocardium infarction sedentary (LDL-MI-S), c) LDLr-/- myocardium infarction submitted to continuous training (LDL-MI-C), d) LDLr-/- myocardium infarction submitted to interval training (LDLMI- I), e) sedentary WT (WT-S); f) WT myocardium infarction sedentary (WT-MI-S); g) WT myocardium infarction submitted to continuous training (WT-MI-C), h) WT myocardium infarction submitted to interval training (WT-IM-I). After 60 days of descending coronary artery ligation, the continuous training consisted of running at 60% of maximum, while the interval training consisted of eight sprints of 4 min at 80% of maximum and a 4 min recovery at 40% of maximum. In infarcted WT animals, both training programs increased exercise tolerance and promoted decrease of sympathetic-vagal balance and increase of alpha index in similar magnitudes. Nevertheless, the interval training reduced the number of type II fibers in infarcted WT animals compared to WT-S and WT-MI-C groups, as well as reduced the amount of fiber type II-X compared to WT-S. The cross-sectional area of the fiber type I was higher in the WTMI- I animals than in WT-MI-S and S-WT groups. The reason capillary/fiber was higher in group WT-I than in the WT-S. Ejection fraction and shortening fraction were lower in LDL-MII compared to the others, but with no differences among the WT-S, WT-IMI-C and WT-MI-I groups. About the LDL-/- animals, the LDL was higher and VLDL was lower in the group LDL-MI-C in relation to the others. The HDLtg (%) was higher in LDL-C compared to LDL-S. The HDLc (mg and %) of LDL-MI-I was higher than the LDL-MI-C group, and the HDLc (mg) of LDL-MI-I was even higher than LDL-S group. The total triglycerides was lower in LDL- MIC than in LDL-S animals. Only in LDL-MI-I group the resting HR was decreased in comparison to LDL-MI-S. The diastolic blood pressure was lower in LDL-MI-S in relation to LDL-S, while the LDL-MI-I group presented a higher diastolic BP than the LDL-MI-C group. The pulse interval variance was greater in LDL-S than in LDL-MI-I only. In conclusion, our results demonstrate that LDL animals have important functional and physiological differences compared to WT, especially in relation to muscle morphology, hemodynamic and autonomic cardiovascular control. Furthermore, MI leads to damage in both investigated strains and the two types of physical training attenuate similarly the impairment of most of the analyzed variables

BackgroundThe prompt seeking of medical care after the onset of symptoms suggestive of acute coronary syndromes (ACS)/acute myocardial infarction (AMI) is associated with the receipt of coronary reperfusion therapy, and effective cardiac medications in patients with an ACS/AMI and is crucial to reducing mortality and the risk of serious clinical complications in these patients. Despite declines in important hospital complications and short-term death rates in patients hospitalized with an ACS/AMI, several patient groups remain at increased risk for these adverse outcomes, including women and the elderly. However, recent trends in age and sex differences in extent of pre-hospital delay, hospital management practices, and short-term outcomes associated with ACS/AMI remain unexplored. The objectives of this study were to examine the overall magnitude, and changing trends therein, of age and sex differences in duration of pre-hospital delay (1986-2005), hospital management practices (1999-2007), and short-terms outcomes (1975-2005) in patients hospitalized with ACS/AMI. MethodsData from 13,663 residents of the Worcester, MA, metropolitan area hospitalized at all greater Worcester medical centers for AMI 15 biennial periods between 1975 and 2005 (Worcester Heart Attack Study), and from 50,096 patients hospitalized with an ACS in 106 medical centers in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007 were used for this investigation. Results In comparison with men years, patients in other age-sex strata exhibited significantly longer pre-hospital delay, with the exception of women < 65 years; had a significantly lower odds of receiving aspirin, angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta blockers, statins, and undergoing coronary artery bypass graft surgery (CABG) surgery or percutaneous coronary intervention (PCI), and were significantly more likely to develop atrial fibrillation, cardiogenic shock, heart failure, and to die during hospitalization and in the first 30 days after admission. There was a significant interaction between age and sex in relation to the use of several medications and the development of several of these outcomes; in patients Conclusions Our results suggest that the elderly were more likely to experience longer prehospital delay, were less likely to be treated with evidence-based treatments during hospitalization for acute coronary syndrome, and were more likely to develop adverse outcomes compared to younger persons. Younger women were less likely to be treated with effective treatments and were more likely to develop adverse outcomes compared with younger men while there was no sex difference in these outcomes. Interventions targeted at older patients, in particular, are needed to encourage these high-risk patients to seek medical care promptly to maximize the benefits of currently available treatment modalities. More targeted treatment approaches during hospitalization for ACS/AMI for younger women and older patients are needed to improve their hospital prognosis.

Background: Cognitive impairment is prevalent in survivors of acute coronary syndrome (ACS) and increases risk for poor outcomes. Lifestyle changes are recommended to patients after ACS to reduce their risk for recurrent events, but cognitively impaired patients may encounter difficulties initiating these changes. This dissertation had three aims: (1) to examine cognitive status as a predictor of lifestyle changes after ACS, (2) to examine whether caregiver support moderates the association of cognitive status and initiation of lifestyle changes, and (3) to assess the reliability of self-reported lifestyle changes in cognitively impaired patients through comparison of their reports of lifestyle change with those from their caregivers. Methods: For aims 1 and 2, Poisson regression with robust error variance was used to examine the association of cognitive status and caregiver support with patient-reported initiation of five lifestyle changes (improving diet, increasing exercise, quitting smoking, reducing stress, and attending cardiac rehabilitation) in 881 patients from TRACE-CORE, a prospective longitudinal observational study of outcomes in ACS. For aim 3, pilot data from 78 patient-caregiver dyads from TRACE-CARE, an ancillary substudy, were used to examine whether patient-caregiver congruence on reports of lifestyle changes varied according to patients’ cognitive function. Results: Patient-reported rates of lifestyle change did not vary according to cognitive status, except for participation in cardiac rehabilitation. Caregiver support improved patient-reported rates of lifestyle change among cognitively intact patients but not cognitively impaired patients. Patients’ cognitive function was positively associated with patient-caregiver congruence on reports of initiation of lifestyle changes and patients with decreased cognitive function tended to over-report initiation of lifestyle changes compared to reports by their caregivers. Conclusion: Although cognitive status was not associated with initiation of most lifestyle changes and the influence of caregiver support on initiation of lifestyle changes was only beneficial to cognitively intact patients in this cohort of ACS patients, these null findings may be explained by the questionable validity of self-report in cognitively impaired patients. This dissertation yields new knowledge about secondary prevention in ACS patients and provides insight into the challenges of conducting patient-reported outcomes research in cognitively compromised populations.

Limited data exists describing the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to currently recommended ejection fraction (EF) findings. In addition, little is known about the magnitude of, and factors associated with, long-term prognosis for these patients. Based on previously validated and clinically relevant criteria, we defined HF-REF as patients with an EF value ≤40%, HF-PEF was defined as an EF value > 50%, and HF-BREF was defined as patients with an EF value during their index hospitalization between 41 and 49%. The hospital medical records of residents of the Worcester (MA) metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during the 5 study years of 1995, 2000, 2002, 2004, and 2006 were reviewed. Follow-up was completed through 2011 for all patient cohorts. The average age of this population was 75 years, the majority was white, and 44% were men. Patients with HF-PEF experienced higher post discharge survival rates than patients with either HF-REF or HF-BREF at 1, 2, and 5-years after discharge. Advanced age and lower estimated glomerular filtration rate findings at the time of hospital admission were important predictors of 1-year death rates, irrespective of EF findings. Previously diagnosed chronic obstructive pulmonary disease, chronic kidney disease, and atrial fibrillation were associated with a poor prognosis in patients with PEF and REF whereas a history of diabetes was an important prognostic factor for patients with REF and BREF. In conclusion, although improvements in 1-year post-discharge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the post- 7 discharge prognosis of all patients with ADHF remains guarded. In addition, we observed differences in several prognostic factors between patients with ADHF with varying EF findings, which have implications for more refined treatment and surveillance plans for these patients.

Cette thèse répond à un double objectif, elle s’est concentrée d’une part sur le rôle joué par l’énergie dans le développement industrielle et économique des pays et d’autres parts sur les retombées de son usage sur l’environnement et l’état de santé des individus. Nous avons élaboré et exploité une base de données relative à la région de Sfax, qui a été utilisée pour l’analyse empirique adaptée à chaque axe de recherche. Le cheminement suivi pour argumenter cette thèse nous a amené à constituer trois chapitres. Au niveau du premier chapitre, nous avons particulièrement apprécié le rôle que l’énergie a préoccupé dans le développement économique des nations. Suite à notre analyse empirique, deux résultats principaux sont annoncés, d’abord, la présence d’un effet de long terme entre la consommation de l’énergie et le développement économique dans la région de Sfax impliquant ainsi sa dépendance économique à l’énergie, ensuite, l’existence d’une relation de causalité unidirectionnelle partant de la consommation de l’énergie vers la croissance économique. Dans un deuxième chapitre, nous nous sommes intéressés à étudier l’impact de la consommation de l’énergie sur la détérioration de la qualité de l’environnement. Deux points sont mis en valeur. Premièrement, une corrélation est détectée entre la consommation de l’énergie et les polluants suivants : PM10, SO2 et NO2. Deuxièmement, la présence de l’O3 troposphérique dans l’air n’est pas subordonnée à la consommation de l’énergie mais plutôt aux réactions photochimiques impliquant le NO2 et l’oxygène sous l’effet des rayons solaires ultra-violets. Finalement, les facteurs météorologiques et surtout la température (T) et l’humidité relative (HR) agissent sur la dispersion des polluants et leur accumulation autour de leurs sources d’émissions. Le dernier chapitre s’est focalisé sur l’analyse de l’impact sanitaire de la pollution atmosphérique. Adapté au contexte de la région de Sfax, trois constats principaux sont détectés. Tout d’abord, les maladies cardiovasculaires sont affectées par les émissions de S02 tandis que les maladies respiratoires sont influencées par les émissions de SO2 et O3. Ensuite, une corrélation est justifiée entre l’O3 te le NO2 qui confirme la réaction chimique de piégeage de l’ozone déjà indiquée. Enfin, nous avons déduit que la vitesse de vent (VV) impacte la distribution des polluants principalement le NO2, le SO2 et les PM10. La température (T) affecte à son tour les admissions hospitalières pour motif cardiovasculaire. / This thesis has a dual purpose; it focused on the one hand on the role of energy in the industrial and economic development of the country and on the other hand on the impact of its use on the environment and health status of individuals. We developed and operated a database on the Sfax region, which has been used for empirical analysis suited to each area of ​​research. The path followed to argue this thesis has led us to establish three chapters.At the first chapter, we particularly appreciated the role of energy in economic development of nations. Following our empirical analysis, two main results are announced, first, the presence of a long-term effect between energy consumption and economic development in the region of Sfax implying its economic dependence on energy. Then the existence of unidirectional causal relationship starting from energy consumption to economic growth. In the second chapter, we are interested in studying the impact of energy consumption on the deterioration of the environment quality. Two points are emphasized, first, a correlation is found between energy consumption and the following pollutants: PM10, SO2 and NO2. Secondly, the presence of tropospheric ozone (O3) in the air is not conditional on the energy consumption but rather to photochemical reactions involving NO2 and oxygen under the influence of solar ultraviolet radiation. Finally, weather factors, especially temperature (T) and relative humidity (RH) affect the dispersion of pollutants and their accumulation around their emission sources. The last chapter is focused on the analysis of the health impact of air pollution. Adapted to the region of Sfax, three main findings are detected. First, cardiovascular diseases are affected by S02 emissions and while respiratory diseases are influenced by emissions of SO2 and O3. Then, a correlation is justified between O3 NO2, confirming the chemical reaction of ozone scavenging already indicated. Finally, we concluded that the wind speed (VV) affects the distribution of pollutants mainly NO2, SO2 and PM10. Temperature (T) in turn affects hospital admissions for cardiovascular reasons.

Selected aspects of the mortality development in the USA since the turn of the millennium Abstract The main goal of the thesis was to analyze the development of mortality from selected causes in the USA between the years 1999 and 2019. The selected causes are long-term leading causes of death in the USA. These include cardiovascular diseases, malignant neoplasms, chronic lower respiratory diseases, external causes and cerebrovascular diseases. The current disease covid-19 was included in the selected causes of death, as according to preliminary data, it was the third leading cause of death in the USA in the year 2020. The first part presents the mortality rates in the USA from different perspectives to create the context of the current development of mortality trends and also characterizes the individual causes of death, which are then addressed in the analytical part of the thesis. Furthermore, the healthcare system of the USA is described, as it is one of the factors influencing the mortality rate and also because it differs significantly from the systems known in Europe. The second part presents the development of mortality from selected causes of death, according to sex and individual US states. Methods used in the analytical part of the thesis were the gross mortality rate, direct and indirect...