Coronary heart disease is the single greatest contributor to mortality within developed countries in our time. Type 2 diabetes mellitus and obesity, both of which are potent risk factors for coronary heart disease, are common conditions with rapidly rising rates of prevalence both globally and in Australia. Within Australia, Indigenous Australians suffer from disproportionately high rates of diabetes, obesity and coronary heart disease, the reason for which lies, in part, with changes in dietary intake and decreased levels of physical activity over the past 200 years. These disease trends have led to a substantially reduced life expectancy from an increase in excess cardiovascular deaths in Indigenous Australians. Assessment of cardiovascular risk in Indigenous Australians is complicated by ethnic differences in cardiovascular risk factors and their prevalence. There is also evidence that Indigenous Australians are genetically predisposed to diabetes. Current cardiovascular risk stratification algorithms are suboptimal, significantly underestimating risk in Indigenous Australians. This thesis aimed to address these issues. Firstly, to evaluate the efficacy of a lifestyle intervention programme to sustainably improve markers of health outcome in a cohort of Indigenous Australians who were overweight or had type 2 diabetes mellitus by improving diet and physical activity levels. Secondly, to evaluate the utility of anthropometric markers of obesity, ultrasound markers of atherosclerotic burden and serum C-reactive protein as additional cardiovascular risk stratification tools. The Healthy Lifestyle Programme (HELP) was a two year prospective intervention study designed and implemented with substantial input from the Indigenous community. The primary intervention consisted of a series of educational workshops delivered predominantly by Indigenous health workers advocating improving diet and increasing physical activity. To complement these workshops, facilities were established within the community to support dietary improvement and increased physical activity. Sustainable changes to markers of cardiovascular outcome, including significant reductions in central obesity and blood pressure were demonstrated over time. A slowing in the deterioration of renal function as marked by albuminuria was also detected. These beneficial changes were accompanied by increased physical activity and improved dietary intake. In a substudy, individuals with the apolipoprotein E4 genotype, who were dyslipidaemic at baseline, benefited from lipid profiles that improved significantly during the course of the study. Changes in blood pressure and central obesity detected during the course of the project are likely to have significant clinical impact on health outcomes considering their sustained nature. Evaluating ultrasound imaging based markers of cardiovascular risk, carotid artery intimal medial thickness was a more reliable measure of risk based on its firm correlation with established cardiovascular risk factors compared to brachial artery flow mediated vasodilatation. Carotid artery intimal medial thickness may be the better surrogate marker to improve cardiovascular risk stratification in the Indigenous population. Examining anthropometric markers of obesity, body mass index and waist circumference but not waist hip ratio correlated well with traditional cardiovascular risk factors. Furthermore, both body mass index and waist circumference predicted insulin resistance fairly well using threshold values derived from receiver operating characteristics curve analyses. Both body mass index and waist circumference were simple to perform with a high degree of reproducibility between observers and will likely be valuable additional cardiovascular risk stratification tools. Raised inflammatory stress, as marked by elevated serum C-reactive protein levels, was found in individuals with diabetes or obesity. C-reactive protein levels did not correlate with carotid artery intimal medial thickness, suggesting that C-reactive protein raises cardiovascular risk by means other than increasing atherosclerotic burden. Genotyping a small random sample of our the C-reactive protein gene promoter region. This SNP was found to independently increase serum C-reactive protein in the Framingham cohort. A genetic basis for increased inflammatory stress may contribute to coronary heart disease in Indigenous Australians. In summary, a community centred lifestyle intervention programme was efficacious in producing sustainable improvement in markers of health outcome. Examination of additional cardiovascular risk markers in the Indigenous community have provided evidence for using carotid artery intimal medial thickness, waist circumference, body mass index and serum C-reactive protein levels to improve cardiovascular risk stratification. These additional tools would allow for more specific resource allocation to target individuals at highest cardiovascular risk for preventative management. C-reactive protein gene polymorphisms, their contribution to circulating C-reactive protein levels and cardiovascular outcomes warrants further investigation in the Indigenous population. A more proactive risk management plan, which includes a lifestyle intervention component, may yield the greatest improvement in long term health outcomes if targeted at younger members of the Indigenous community.

Coronary heart disease is the single greatest contributor to mortality within developed countries in our time. Type 2 diabetes mellitus and obesity, both of which are potent risk factors for coronary heart disease, are common conditions with rapidly rising rates of prevalence both globally and in Australia. Within Australia, Indigenous Australians suffer from disproportionately high rates of diabetes, obesity and coronary heart disease, the reason for which lies, in part, with changes in dietary intake and decreased levels of physical activity over the past 200 years. These disease trends have led to a substantially reduced life expectancy from an increase in excess cardiovascular deaths in Indigenous Australians. Assessment of cardiovascular risk in Indigenous Australians is complicated by ethnic differences in cardiovascular risk factors and their prevalence. There is also evidence that Indigenous Australians are genetically predisposed to diabetes. Current cardiovascular risk stratification algorithms are suboptimal, significantly underestimating risk in Indigenous Australians. This thesis aimed to address these issues. Firstly, to evaluate the efficacy of a lifestyle intervention programme to sustainably improve markers of health outcome in a cohort of Indigenous Australians who were overweight or had type 2 diabetes mellitus by improving diet and physical activity levels. Secondly, to evaluate the utility of anthropometric markers of obesity, ultrasound markers of atherosclerotic burden and serum C-reactive protein as additional cardiovascular risk stratification tools. The Healthy Lifestyle Programme (HELP) was a two year prospective intervention study designed and implemented with substantial input from the Indigenous community. The primary intervention consisted of a series of educational workshops delivered predominantly by Indigenous health workers advocating improving diet and increasing physical activity. To complement these workshops, facilities were established within the community to support dietary improvement and increased physical activity. Sustainable changes to markers of cardiovascular outcome, including significant reductions in central obesity and blood pressure were demonstrated over time. A slowing in the deterioration of renal function as marked by albuminuria was also detected. These beneficial changes were accompanied by increased physical activity and improved dietary intake. In a substudy, individuals with the apolipoprotein E4 genotype, who were dyslipidaemic at baseline, benefited from lipid profiles that improved significantly during the course of the study. Changes in blood pressure and central obesity detected during the course of the project are likely to have significant clinical impact on health outcomes considering their sustained nature. Evaluating ultrasound imaging based markers of cardiovascular risk, carotid artery intimal medial thickness was a more reliable measure of risk based on its firm correlation with established cardiovascular risk factors compared to brachial artery flow mediated vasodilatation. Carotid artery intimal medial thickness may be the better surrogate marker to improve cardiovascular risk stratification in the Indigenous population. Examining anthropometric markers of obesity, body mass index and waist circumference but not waist hip ratio correlated well with traditional cardiovascular risk factors. Furthermore, both body mass index and waist circumference predicted insulin resistance fairly well using threshold values derived from receiver operating characteristics curve analyses. Both body mass index and waist circumference were simple to perform with a high degree of reproducibility between observers and will likely be valuable additional cardiovascular risk stratification tools. Raised inflammatory stress, as marked by elevated serum C-reactive protein levels, was found in individuals with diabetes or obesity. C-reactive protein levels did not correlate with carotid artery intimal medial thickness, suggesting that C-reactive protein raises cardiovascular risk by means other than increasing atherosclerotic burden. Genotyping a small random sample of our the C-reactive protein gene promoter region. This SNP was found to independently increase serum C-reactive protein in the Framingham cohort. A genetic basis for increased inflammatory stress may contribute to coronary heart disease in Indigenous Australians. In summary, a community centred lifestyle intervention programme was efficacious in producing sustainable improvement in markers of health outcome. Examination of additional cardiovascular risk markers in the Indigenous community have provided evidence for using carotid artery intimal medial thickness, waist circumference, body mass index and serum C-reactive protein levels to improve cardiovascular risk stratification. These additional tools would allow for more specific resource allocation to target individuals at highest cardiovascular risk for preventative management. C-reactive protein gene polymorphisms, their contribution to circulating C-reactive protein levels and cardiovascular outcomes warrants further investigation in the Indigenous population. A more proactive risk management plan, which includes a lifestyle intervention component, may yield the greatest improvement in long term health outcomes if targeted at younger members of the Indigenous community.

A prevalência de sobrepeso e obesidade entre crianças e adolescentes tem aumentado em países em desenvolvimento e desenvolvidos, ocasionando um sério problema de saúde pública. A obesidade na adolescência pode alterar o perfil lipídico, principalmente quando acompanhada de uma baixa aptidão cardiorrespiratória. A obesidade, bem como as dislipidemias são considerados importantes fatores de risco para a doença arterial coronariana. O presente estudo teve como objetivo avaliar a correlação entre o perfil lipídico, bem como outros marcadores de risco para doença arterial coronariana, e a aptidão cardiorrespiratória de crianças e adolescentes obesos, de ambos os gêneros. Um total de 63 crianças e adolescentes obesos, entre 11 e 17 anos, foi incluído em um estudo transversal, realizado na cidade de Porto Alegre. Foi utilizado o pacote estatístico SPSS, versão 10.0 para Windows. Foram aplicados o teste t para amostras independentes e o teste de Mann-Whitney para identificar diferenças entre gêneros e estágio maturacional quando a distribuição apresentava-se normal e não-normal, respectivamente. Utilizou-se a correlação de Pearson ou Spearman para dados paramétricos e não-paramétricos, respectivamente. Não encontramos correlação significativa entre o pic2 o V& O e os marcadores de risco para doença coronariana TG, CT, HDL-C, LDL-C, ApoA1, ApoB, Não-HDL-C, CT/HDL, LDL-C/HDL-C, insulina, glicose, índice HOMA-IR e PCRus. Do total de crianças e adolescentes avaliados, somente um indivíduo, do gênero masculino, não apresentava nenhum parâmetro metabólico alterado. Encontramos uma prevalência precoce importante de indivíduos com hipercolesterolemia (15,0%); hipertrigliceridemia (23,3%); hiperglicemia (35,6%); hiperinsulinemia (40,4%); valores altos de LDL-C (16,7%), PCRus (38,3%) e Não-HDL-C (26,7%); e valores baixos de HDL-C (21,7%) e do VO2pico (93,5% da meninas e 100% dos meninos). Concluindo, apesar de não encontrarmos correlação significativa entre o perfil lipídico e a aptidão cardiorrespiratória de crianças e adolescentes obesos neste estudo, uma prevalência alta de dislipidemias e outros marcadores de risco coronariano alterados foram encontrados. / The prevalence of overweight children and adolescents has been increasing in both developed and developing countries, creating a serious public health problem. Obesity in adolescence can alter the lipid profile mainly when accompanied by a low cardiorespiratory fitness. Obesity and dislipidemy are well-established risk factors for the coronary artery disease. The aim of the present study was to evaluate the correlation among the lipid profile, as well as other risk markers for the coronary artery disease, and the cardiorespiratory fitness of obese children and adolescents of both genders. A total of 63 children and adolescents between 11 and 17 years old were included in this cross-sectional study, developed in the city of Porto Alegre. Statistical analysis was performed by the software SPSS, version 10.0 for Windows. The T-test for independent samples and the Mann-Whitney test were applied to identify differences among gender and pubertal stage when the distribution was normal and abnormal, respectively. The Pearson’s or the Spearman’s correlation was used for parametric and nonparametric data, respectively. We did not find significant correlation between pea2 k V& O and the risk markers for the coronary disease TG, TC, HDL-C, LDL-C, non-HDL-C, TC/HDL, insulin, glucose, HOMA-IR values, and PCRus. Among all individuals evaluated, only one person – a male – did not show any altered metabolic parameter. We found an important precocious prevalence of individuals with hypercholesterolemia (15%); hypertriglyceridemia (23.3%); borderline hyperglycemia (35.6%); hyperinsulinemia (40.4%); high values of LDLC (16.7%), PCRus (38.3%), non-HDL-C (26.7%); and low values of HDL-C (21.7%) and 2 peak V& O (93.5% of the girls and 100% of the boys). In conclusion, although we did not find any significant correlation between lipid profile and cardiorespiratory fitness in obese children of both genders in this study, a high prevalence of undesirable lipid levels and other altered coronary risk markers were found.

Background. The incidence of starting renal replacement therapy (RRT) among young people (< 20 years of age) in 2013 in Scotland was 7.7 per million (age-related) population. Little knowledge exists about cardiovascular risk factors (CVRFs), long-term survival and cardiovascular disease (CVD) outcomes in patients who initiated RRT in childhood. The main source of routine data for these patients is available from the European Society of Paediatric Nephrology/European Renal Association- European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry. In Scotland nationally comprehensive data on patients receiving RRT is available from the Scottish Renal Registry (SRR). Aim and objectives. The overall aim of the thesis is to review relevant literature and conduct retrospective cohort studies describing CVRF prevalence, all-cause mortality and incidence of CVD outcomes in patients who initiated RRT in childhood. ESPN/ERA-EDTA registry data were used to describe the prevalence of anaemia, hypertension, dyslipidaemia and BMI categories and their association with all-cause and CV mortality. SRR data were used to describe all-cause mortality and CVD incidence and their association with age at start of RRT, sex, primary renal disease (PRD), type of RRT and period of start of RRT. Methods. Systematic searches were performed to identify relevant literature. For the ESPN/ERA-EDTA analyses patients who started RRT between 0 and 20 years of age and who had CVRF data were included. Patients were followed from date of first CVRF measurement until the earliest of death, loss to follow-up, reaching 20 years of age or the end of follow-up (December 31st 2012). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality, comparing patients with and without each CVRF. For the SRR analyses, patients who started RRT under 18 years of age in the period from 1963 to 2013 were included in the analyses. To describe CVD incidence the SRR data were linked to national registers for death and CVD hospital admissions available from 1981 onwards. These analyses, therefore, included patients who started RRT between 1981 and 2013 with follow-up until first CVD event after start of RRT, end of follow-up period or censoring at death. Cox proportional hazard models were used to examine the association of age at initiation of RRT, sex, PRD, type of RRT and period of initiation of RRT with all-cause mortality and CVD incidence. Results. The systematic reviews revealed a gap in current knowledge about CVD incidence and the association of CVRFs with CVD outcomes in patients who initiated RRT in childhood. In total, 7,845 patients were included in the ESPN/ERA-EDTA registry analysis. The mean age of the patients was 9.5 (SE 0.06) years, 58.9% were male, and the most common PRD was congenital anomalies of kidney and urinary tract (CAKUT). The prevalence of dyslipidaemia, hypertension, anaemia overweight/obesity and underweight was 87.5%, 79.3%, 36.0%, 29.9% and 4.3%, respectively. During median follow-up of 3.7 (IQR 1.7-6.8) years 357 patients died. HRs for anaemia were 2.19 (95% CI 1.64-2.93) and 2.55 (95% CI 1.27-5.12) for all-cause and CVD mortality, respectively. The HR for all-cause mortality for underweight was 1.81 (95% CI 1.30-2.53). No other studied CVRFs were statistically significantly associated with all-cause and CVD mortality. In total, 479 patients were included in the SRR analyses of all-cause mortality. The most common PRD was CAKUT and 55.3% of patients were male. During a median follow-up of 18.3 (IQR 8.7-27.0 years) years 126 patients died. Twenty-year survival among patients initiated RRT in childhood was 77.6% (95% CI 73.8-81.3). Age at start of RRT, PRD and type of RRT were significantly associated with all-cause mortality. HR for all-cause mortality for patients who started RRT under 2 years of age was 2.50 (95% CI 1.19-5.25) compared to patients who started RRT at 12 to 18 years old. HR for all-cause mortality for patients with PRD other than CAKUT or glomerulonephritis (GN) was 1.58 (95% CI 1.05-2.39) compared to patients with CAKUT. HRs for all-cause mortality for patients who only received either HD or PD during follow-up were 19.4 (95% CI 10.4-36.4 and 19.5 (9.65-39.7), respectively, compared to patients who received a renal transplant. In total, 381 patients were included in the SRR analyses of CVD incidence. During a median of 12.9 (IQR 5.6-21.5) years of follow-up after initiation of RRT 134 patients (35.2%) developed CVD. The overall crude CVD incidence was 2.6 (95% CI 2.2-3.0) per 100 person-years. HRs for CVD were 1.69 (95% CI 1.05-2.74) for males compared to females, 1.72 (95% CI 1.02-2.91) for PRD other than CAKUT or GN compared to CAKUT and 8.38 (95% CI 3.31-21.23) and 7.30 (95% CI 2.30-23.16) for patients who only received either HD or PD during follow-up, respectively, compared to patients who received a renal transplant. Conclusions. This thesis has contributed to knowledge about CVRF prevalence, longer-term survival and CVD outcomes in patients who initiated RRT in childhood by identifying high prevalence of CVRFs and that CVD is a common complication. This study did not investigate whether anaemia, hypertension, dyslipidaemia and obesity are associated with a higher risk of developing CVD after start of RRT. Future research is needed to study whether treatment of anaemia, hypertension, dyslipidaemia and controlling body weight will reduce the risk of CVD and mortality in patients who initiated RRT in childhood.

Introduction. L’Enquête Littoral Souffle Air Biologie Environnement (ELISABET) a pour objectif général l’étude de la santé respiratoire et cardiovasculaire dans les communautés urbaines de Lille (CUDL) et Dunkerque (CUD). Les objectifs spécifiques de cette thèse sont d’étudier : (i) la prévalence et le sous-diagnostic des troubles ventilatoires obstructifs (TVO), (ii) l’évolution de la prévalence des principaux facteurs de risque cardiovasculaire (FDRCV) dans la CUDL entre 1986 et 2013, (iii) les interactions entre deux biomarqueurs de l’asthme (fraction exhalée du monoxyde d’azote (FENO) et taux d’éosinophiles sanguin (S-eos)) et le statut tabagique, (iv) le rôle de médiateur de l’inflammation chronique de bas-grade dans la relation entre diabète et baisse de la fonction pulmonaire, et (v) l’impact à court terme de la pollution atmosphérique sur la fonction respiratoire.Méthodes. Les 3276 participants (âgés de 40 à 65 ans) à l’enquête transversale en ELISABET ont été sélectionnés à partir de listes électorales par échantillonnage aléatoire et inclus entre janvier 2011 et novembre 2013. Un questionnaire détaillé, des explorations fonctionnelles respiratoires et un prélèvement sanguin ont été effectués. (i) Les TVO ont été définis par un rapport du volume expiratoire maximal à la première seconde (VEMS) sur la capacité vitale forcée (CVF) inférieur à 0.70 ou à la limite inférieure de la normale calculée à partir des dernières équations de référence disponibles. (ii) La prévalence des principaux FDRCV a été estimée à partir d’échantillons représentatifs de la population de la CUDL issus des enquêtes MONICA1986-88, MONICA1995-96, MONALISA2005-07 et ELISABET2011-13. (iii) L’asthme allergique a été défini comme un asthme (auto-déclaration, et sifflements dans la poitrine dans les 12 derniers mois ou prise de traitement) avec terrain atopique. (iv) Le diabète était défini par la prise d’un traitement antidiabétique ou une glycémie à jeun ≥ 1.26 g/L ou des valeurs d’hémoglobine A1c ≥ 6.5%. L’inflammation chronique a été mesurée par la Protéine C réactive ultra-sensible (CRPus). Une analyse de médiation a été conduite sur un échantillon de sujets sans pathologie respiratoire ou athérosclérotique. (v) Les valeurs des particules inférieures à 10 µm (PM10) et du dioxyde d'azote (NO2) ont été fournies par les stations de mesures ATMO des CUDL et CUD.Principaux résultats. (i) La prévalence des TVO s’étendait de 9.5% à 16% (dépendant du centre et de la définition utilisée) ; le taux de sous-diagnostic était élevé (environ 75 %). (ii) La prévalence des principaux FDRCV diminuait régulièrement sur une période de 25 ans, à l'exception de l'usage du tabac chez les femmes, du diabète chez les hommes (tous deux stables) et de la surcharge pondérale chez les hommes (augmentée). (iii) Une interaction positive entre le statut tabagique et l'asthme allergique a été observée dans les modèles expliquant le FENO (p = 0,003) et les S-eos (p = 0,001). Ainsi, les participants souffrant d'asthme allergique avaient (comparés à ceux n’en souffrant pas) des valeurs plus élevées de FENO (+ 63,4 %, IC95% = [39; 92]) et de S-eos (+ 63,2 % [38,2; 92,7]) chez les non-fumeurs, mais pas chez les fumeurs actuels. (iv) Le diabète était associé à une diminution des pourcentages prédits du VEMS (-3.5% [-5.8; -1.3]) et de la CVF (-3.6% [-5.9; -1.3]). La force de ces associations diminuait (-3.1% [-5.4; -0.9] pour les deux) après ajustement sur la CRPus. Ainsi, la part médiée de la CRPus valait 12% [2.4; 37] et 13% [3.7; 39.4] pour le VEMS et la CVF, respectivement. (v) Les mesures de PM10 et NO2 semblaient associées à une diminution du débit expiratoire maximal à 25 % de la CVF (résultat préliminaire).Conclusion. Les données de l’enquête ELISABET ont permis l’étude de la prévalence des TVO et des principaux FDRCV au sein de notre population d’étude. Elles ont également permis d’obtenir des résultats originaux à partir d’études cliniques et physiopathologiques. / Introduction. The general goal of the ELISABET (Enquête Littoral Souffle Air Biologie Environnement) survey is to study the respiratory and cardiovascular health in two urban areas in northern France (Lille and Dunkirk). The specific objectives of this thesis are to study: (i) the prevalence and underdiagnosis of airway obstruction (AO), (ii) long-term time trends in the prevalence of cardiovascular risk factors between 1986 and 2013 in the Lille urban area, (iii) the relationships between both the fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B-eos) on one hand and asthma and atopy on the other, according to smoking status, (iv) whether low-grade systemic inflammation (as measured by the level of high sensitivity-C-reactive protein, hs-CRP) mediated the relationship between diabetes and lung function, and (v) the short-term impact of atmospheric pollution on lung function.Methods. The 3276 participants (aged from 40 to 64) in the 2011-2013 ELISABET cross-sectional survey were selected from electoral rolls by random sampling, and recruited between January 2011 and November 2013. A detailed questionnaire, lung function tests, and a blood sample collection were performed. (i) AO was defined by a forced expiratory volume in the first second (FEV1) to forced vital capacity (FVC) ratio below 0.70 or below the lower limit of normal calculated by the most recent reference equations of the Global Lung Initiative. (ii) The prevalence of the main cardiovascular risk factors was estimated from representative samples inhabitants of Lille urban area from MONICA1986-88, MONICA1995-96, MONALISA2005-07 and ELISABET2011-13 surveys. (iii) Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy. (iv) Diabetes mellitus was defined as ongoing diabetes treatment or a fasting blood glucose level ≥1.26 g/L or a hemoglobin A1c value ≥6.5%. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function from a sample of participants without self-reported pulmonary and atherosclerotic disease. (v) Measurements of particles less than 10 mm in diameter (PM10) and nitrogen dioxide (NO2) were provided by measuring stations ATMO in the two urban areas.Main results. (i) The prevalence of AO in northern France ranged from 9.5 to 16.0%, depending on the centre and definition used; the underdiagnosis rate was high (around 75%). (ii) A steady decline in the prevalence of cardiovascular risk factors over a 25-year period was observed, with the exception of tobacco use in women, prevalence of diabetes in men (both of which remained stable) and prevalence of overweight in men (which increased). (iii) A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO (p=0.003) and B-eos (p=0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+63.4%, 95%CI=[39; 92]) and higher B-eos (+63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. (iv) Diabetes was associated with FEV1 (-3.5% [-5.8; -1.3]) and FVC (-3.6% [-5.9; -1.3]). Strength of both latter associations fell to -3.1% [-5.4; -0.9] after adjustment for hs-CRP. Hence, the proportion of the effect that is mediated by hs-CRP was 12% [2.4; 37] and 13% [3.7; 39.4] for FEV1 and FVC, respectively. (v) Measurements of PM10 and NO2 seemed to be associated with lower values of the expiratory flow at 25% of the FVC (preliminary result).Conclusion. Data from the ELISABET survey have allowed the study of the prevalence of AO and the main cardiovascular risk factors in our population. They also allowed obtaining original results from clinical and pathophysiological studies.

A prevalência de sobrepeso e obesidade entre crianças e adolescentes tem aumentado em países em desenvolvimento e desenvolvidos, ocasionando um sério problema de saúde pública. A obesidade na adolescência pode alterar o perfil lipídico, principalmente quando acompanhada de uma baixa aptidão cardiorrespiratória. A obesidade, bem como as dislipidemias são considerados importantes fatores de risco para a doença arterial coronariana. O presente estudo teve como objetivo avaliar a correlação entre o perfil lipídico, bem como outros marcadores de risco para doença arterial coronariana, e a aptidão cardiorrespiratória de crianças e adolescentes obesos, de ambos os gêneros. Um total de 63 crianças e adolescentes obesos, entre 11 e 17 anos, foi incluído em um estudo transversal, realizado na cidade de Porto Alegre. Foi utilizado o pacote estatístico SPSS, versão 10.0 para Windows. Foram aplicados o teste t para amostras independentes e o teste de Mann-Whitney para identificar diferenças entre gêneros e estágio maturacional quando a distribuição apresentava-se normal e não-normal, respectivamente. Utilizou-se a correlação de Pearson ou Spearman para dados paramétricos e não-paramétricos, respectivamente. Não encontramos correlação significativa entre o pic2 o V& O e os marcadores de risco para doença coronariana TG, CT, HDL-C, LDL-C, ApoA1, ApoB, Não-HDL-C, CT/HDL, LDL-C/HDL-C, insulina, glicose, índice HOMA-IR e PCRus. Do total de crianças e adolescentes avaliados, somente um indivíduo, do gênero masculino, não apresentava nenhum parâmetro metabólico alterado. Encontramos uma prevalência precoce importante de indivíduos com hipercolesterolemia (15,0%); hipertrigliceridemia (23,3%); hiperglicemia (35,6%); hiperinsulinemia (40,4%); valores altos de LDL-C (16,7%), PCRus (38,3%) e Não-HDL-C (26,7%); e valores baixos de HDL-C (21,7%) e do VO2pico (93,5% da meninas e 100% dos meninos). Concluindo, apesar de não encontrarmos correlação significativa entre o perfil lipídico e a aptidão cardiorrespiratória de crianças e adolescentes obesos neste estudo, uma prevalência alta de dislipidemias e outros marcadores de risco coronariano alterados foram encontrados. / The prevalence of overweight children and adolescents has been increasing in both developed and developing countries, creating a serious public health problem. Obesity in adolescence can alter the lipid profile mainly when accompanied by a low cardiorespiratory fitness. Obesity and dislipidemy are well-established risk factors for the coronary artery disease. The aim of the present study was to evaluate the correlation among the lipid profile, as well as other risk markers for the coronary artery disease, and the cardiorespiratory fitness of obese children and adolescents of both genders. A total of 63 children and adolescents between 11 and 17 years old were included in this cross-sectional study, developed in the city of Porto Alegre. Statistical analysis was performed by the software SPSS, version 10.0 for Windows. The T-test for independent samples and the Mann-Whitney test were applied to identify differences among gender and pubertal stage when the distribution was normal and abnormal, respectively. The Pearson’s or the Spearman’s correlation was used for parametric and nonparametric data, respectively. We did not find significant correlation between pea2 k V& O and the risk markers for the coronary disease TG, TC, HDL-C, LDL-C, non-HDL-C, TC/HDL, insulin, glucose, HOMA-IR values, and PCRus. Among all individuals evaluated, only one person – a male – did not show any altered metabolic parameter. We found an important precocious prevalence of individuals with hypercholesterolemia (15%); hypertriglyceridemia (23.3%); borderline hyperglycemia (35.6%); hyperinsulinemia (40.4%); high values of LDLC (16.7%), PCRus (38.3%), non-HDL-C (26.7%); and low values of HDL-C (21.7%) and 2 peak V& O (93.5% of the girls and 100% of the boys). In conclusion, although we did not find any significant correlation between lipid profile and cardiorespiratory fitness in obese children of both genders in this study, a high prevalence of undesirable lipid levels and other altered coronary risk markers were found.

Introdução: Estudos relatam uma maior prevalência de fatores de risco cardiovascular desfavoráveis em indivíduos com migrânea, mas os resultados são conflitantes. Objetivos: Investigar a presença de fatores de risco cardiovascular em mulheres adultas portadoras de migrânea e comparar com controles sadios. Métodos: Cinquenta e nove mulheres participaram deste estudo caso-controle. Sujeitos do estudo foram divididos em grupos de pacientes eutróficas e obesas e comparadas a grupos controle pareados por idade e índice de massa corporal. Níveis séricos de lipídios, glicemia de jejum, insulinemia, resistência à insulina, pressão arterial, tabagismo, atividade física, escore de Framingham, proteína creativa, história familiar de doenças cardiovasculares (DCV), distúrbios do sono, depressão e ângulo de fase por bioimpedância elétrica foram investigados. Resultados: As pacientes obesas com migrânea apresentaram menores valores de HDL-c do que pacientes e controles eutróficas; a resistência à insulina e a insulinemia foram relacionadas à obesidade; todas as pacientes com migrânea eram sedentárias, independentemente de seu estado nutricional; o escore de Framingham foi mais elevado em pacientes obesas com migrânea; pacientes com migrânea tiveram maiores escores de depressão; assim como curta duração do sono, especialmente as obesas. Conclusão: Resultados preliminares apontam nitidamente para sedentarismo e depressão e possíveis distúrbios do sono em pacientes com migrânea, além de plausível sobreposição de efeito da obesidade e da migrânea sobre os níveis séricos de HDL-c e escore de risco de Framingham. / Background: Studies have reported a higher prevalence of unfavorable cardiovascular risk factors amongst migraineurs, but results have been conflicting. Objective: To investigate cardiovascular risk factors in adult women with migraine and compare with health controls. Design and Methods: Fifty nine adult female probands participated in this case-control study. The study group was divided into normal weight and obese migraineurs and control groups matched by age and body mass index. Serum levels of lipids, fasting glucose, insulinemia, insulin resistance, blood pressure, smoking, physical inactivity, Framingham risk, C-reactive protein, family history of cardiovascular disease, sleep disturbances, depression and bioelectrical impedance phase angle were investigated. Results: Obese migraineurs had lower HDL-c than eutrophic controls and migraineurs, insulin resistance and insulinemia were obese-related, all migraineurs were sedentary irrespective of nutritional status, Framingham risk score was higher in obese migraineurs, migraineurs had higher depression scores and shorter sleep duration, obese migraineurs and also migraineurs taken together had worst sleep quality scores. Conclusion: Preliminary results points to marked inactivity, depression and some sleep disturbance in migraine patients, and also probably overlapped effects of obesity and migraine in HDL-c levels and 10-year Framingham general cardiovascular disease risk.

Regular physical activity and a healthful diet are important influences on health. Nevertheless, few studies have focused on the influence of habitual physical activity on diet preferences. The aim of this cross-sectional study was to investigate the relationship between habitual physical activity and dietary intake, body composition, metabolic and hormonal variables and cardiovascular risk factors in postmenopausal women with no evidence of cardiovascular disease. One hundred and five women (mean age: 55.2±4.9 years) consulting for climacteric symptoms underwent anthropometric and hormonal assessment. Usual dietary intake was assessed with a food frequency questionnaire, and habitual physical activity with a digital pedometer. Participants were classified as physically inactive (5 999 steps daily) or physically active (≥ 6 000 steps daily). A negative correlation was observed between steps/day and percent body fat (r = - 0.470; P<0.001), waist circumference (r = - 0.356; P<0.001) and body mass index (r = - 0.286; P=0.003). Compared to the inactive group, active participants had lower diastolic blood pressure (P=0.012), ultrasensitive C-reactive protein (us-CRP) (P=0.011), fasting glucose (P=0.003), fasting insulin (P=0.019) and homeostasis model assessment index (P=0.017), and higher intake of protein, total fat, cholesterol, calcium, iron, zinc, selenium, meats, eggs, and whole-fat dairy foods. After adjustment for age and time since menopause, the risk for metabolic syndrome increased with physical inactivity, high blood pressure, us-CRP, and percent body fat. In conclusion, both habitual physical activity and dietary choices may have contributed towards a more favorable cardiovascular profile and lower risk of metabolic syndrome in postmenopausal women.

O transtorno de humor bipolar (THB) é uma condição incapacitante e caracterizada pela presença de episódios de humor associados a alterações de cognição e de comportamento. Indivíduos com diagnóstico de THB estão particularmente propensos a múltiplas condições metabólicas. Em uma parcela dos pacientes acometidos pela doença observa-se a neuroprogressão do quadro, com alterações no campo da neuroimagem e de biomarcadores – citocinas inflamatórias, estresse oxidativo e neurotrofinas. Tais fatores parecem também relacionar-se ao aumento do risco cardiovascular (RCV) observado nessa população, visto que a doença cardiovascular (DCV) constitui a principal causa de morte em pacientes com THB. Mesmo conhecendo tal estatística, há escassez de literatura científica abordando avaliação cardiovascular em pacientes bipolares. Dessa forma, a presente tese tem o objetivo de melhorar o entendimento da associação entre neuroprogressão e doença cardiovascular. Para tal, inicialmente conduzimos uma revisão da literatura englobando variáveis associadas ao estadiamento e à neuroprogressão, sobretudo aspectos que se referem a biomarcadores, neuroimagem, cognição, funcionalidade e resposta ao tratamento. Em seguida, foi realizado estudo clínico com o objetivo de avaliar a prevalência de doença aterosclerótica coronariana através do uso do escore de cálcio coronariano (ECC) em pacientes ambulatoriais bipolares tipo 1. Os pacientes incluídos eram bipolares tipo 1, todos eutímicos e tendo assinado o termo de consentimento. Os escores de cálcio foram adquiridos utilizando um scanner Aquilion 64 CXL (Toshiba Medical Systems) e a quantificação realizada através do método de Agatston. Em nosso estudo verificou-se que pacientes com ECC positivo eram mais velhos (média 55.2 anos; p=0.001) e tinham uma média maior de internações psiquiátricas prévias (media 4.7; p=0.04) quando comparados ao grupo com ECC negativo, além de também haver uma associação positiva entre ECC e número de internações psiquiátricas prévias entre toda a amostra do estudo (p<0.001). Nossos resultados sugerem a associação entre idade e maiores escores coronarianos, além da relação entre cálcio coronariano e número de internacões psiquiátricas prévias. É possível que este achado relacione-se ao fato de que pacientes em estágios mais avançados da doença tenham maior carga inflamatória que, juntamente com os fatores de risco para DCV, justificaria o aumento do RCV, sugerindo um possível link entre neuroprogressão no THB e aterosclerose coronariana acelerada. / Bipolar disorder (BD) is a disabling condition characterized by the presence of mood episodes associated with changes in cognition and behavior. Individuals diagnosed with BD are particularly prone to multiple metabolic conditions. In a portion of the patients affected by the disease the neuroprogression is observed, with alterations in the field of neuroimaging and of biomarkers - inflammatory cytokines, oxidative stress and neurotrophins. These factors also seem to be related to the increased cardiovascular risk (CVR) observed in this population, since cardiovascular disease (CVD) is the main cause of death in patients with BD. Even knowing this statistic, there is a paucity of scientific literature addressing cardiovascular evaluation in bipolar patients. Thus, the present thesis aims to improve the understanding of the association between neuroprogression and cardiovascular disease. To this objective, we initially conducted a literature review encompassing variables associated with staging and neuroprogression, especially aspects that refer to biomarkers, neuroimaging, cognition, functionality and response to treatment. Afterwards, a clinical study was performed to evaluate the prevalence of coronary atherosclerotic disease through the use of coronary calcium score (CCS) in outpatient bipolar type 1 patients. The patients included were diagnosed as BD type 1, all of them euthymic and signed the consent form. Calcium scores were acquired using an Aquilion 64 CXL scanner (Toshiba Medical Systems) and quantification performed using the Agatston method. In our study, patients with CCS positive were older (mean 55.2 years; p = 0.001) and had a higher mean of previous psychiatric hospitalizations (mean 4.7, p = 0.04) when compared to the CCS negative group, and there was also a positive association between CCS and number of previous psychiatric hospitalizations among the entire study sample (p<0.001). Our results suggest the association between age and higher coronary scores, as well as the relationship between coronary calcium and the number of previous psychiatric hospitalizations. It is possible that this finding is related to the fact that patients in more advanced stages of the disease have a higher inflammatory load that, together with the risk factors for CVD, would justify the increase of CVR, suggesting a possible link between neuroprogression in BD and accelerated coronary atherosclerosis.

Introdução: O trato gastrointestinal humano é composto por uma comunidade microbiana diversificada que atua no controle da saúde. Estudos recentes demonstraram que o equilíbrio da microbiota intestinal é afetado na doença renal crônica (DRC), ocasionando o quadro de disbiose intestinal. Estes estudos sugeriram uma associação da disbiose intestinal com complicações metabólicas como acúmulo de toxinas urêmicas, progressão da DRC, inflamação e risco cardiovascular. Diante disso, medidas com o objetivo de restaurar o equilíbrio da microbiota intestinal são sugeridas, tais como a ingestão oral de probióticos, mas poucos estudos têm abordado o efeito destes suplementos na progressão da DRC e no risco cardiovascular destes pacientes. Objetivo: Avaliar o efeito do consumo de probióticos em fatores associados com progressão da DRC e risco cardiovascular de pacientes com DRC. Material e métodos: Trata-se de um estudo clínico controlado por placebo registrado no Clinical Trials NCT03400228. O estudo incluiu 30 pacientes adultos com DRC nos estágios 3 a 5 não em diálise, com função renal estável e proteinúria igual ou superior a 500 mg. A coleta de dados ocorreu entre novembro de 2015 até dezembro de 2017. O protocolo do estudo constou de período de washout de 4 semanas e randomização dos pacientes para o grupo de intervenção (GI, suplemento com probiótico) ou para o grupo controle (GC, maltodextrina). Foi realizado avaliação basal e após 24 semanas de consumo de probiótico ou placebo. Todos os pacientes receberam a orientação de consumir 2 sachês por dia do probiótico ou do placebo (maltodextrina). Foram avaliadas variáveis demográficas, clínicas, nutricionais, hábito intestinal e exames laboratoriais com amostras sanguíneas e urinárias. Resultados: Dos 30 pacientes incluídos, 20 completaram as 24 semanas do estudo, sendo 10 no grupo intervenção e 10 no grupo placebo. Após o uso de probiótico houve aumento na taxa de filtração glomerular estimada (p<0,001) e diminuição nos níveis séricos de creatinina (p<0,001), ureia (p=0,015), proteína C reativa (p=0,03), hormônio da paratireóide (p=0,03) e potássio (p=0,012), em comparação ao grupo placebo. Os efeitos positivos do probiótico na taxa de filtração glomerular estimada e na diminuição dos níveis séricos de creatinina e ureia permaneceram após análise de regressão multivariada. Não houveram diferenças significativas nos parâmetros urinários entre os grupos. Sintomas de constipação (p<0,001) e consistência fecal (p=0,016) apresentaram melhora no grupo intervenção versus placebo. Conclusão: A suplementação de probióticos melhorou os marcadores de função renal e reduziu inflamação, além de auxiliar na melhora dos sintomas de constipação intestinal em pacientes com DRC. / Introduction: The human gastrointestinal tract is colonized by a diversified microbial community that acts in control of health. Recent studies have shown that intestinal microbiota balance is affected in chronic kidney disease (CKD) leading to intestinal dysbiosis. These studies have suggested association of intestinal dysbiosis with several metabolic disorders such as accumulation of uremic toxins, progression of CKD, inflammation and cardiovascular risk. Therefore, interventional measurement that improve intestinal microbiota balance are suggested such as supplementation of probiotics, however few studies evaluated the effect of these supplements on the progression of CKD and cardiovascular risk in CKD patients. Aim: The purpose of the study was to evaluate the effects of probiotic supplementation on the factors associated with progression of CKD and cardiovascular risk in patients with CKD. Desing and Methods: This was a randomized, double-blind, placebo-controlled study. Thirty patients with CKD stages 3 to 5 not on dialysis, with stable renal function and protein-creatinine ratio > 0.50 were included. Data collection was between November 2015 and December 2017. Study protocol was 4-week washout period, patients randomized to intervention group (IG, probiotic supplement) or control group (CG, maltodextrin), and follow for 24 weeks. Renal function, C-reactive protein (CRP), bone and mineral metabolism, nutritional, and lipid profile markers and intestinal habit were measured at baseline and 24 weeks of study. Results: From 30 patients included in this study, 20 completed the 24 study weeks, 10 in the TG and 10 in PG. After probiotic supplementation, there was increase in estimated glomerular filtration rate (p<0.001) and decrease in serum creatinine 8 (p<0.001), urea (p=0.015), C-reactive protein (p=0.030), parathyroid hormone (p=0.03), and potassium (p=0.012) levels compared to CG. The beneficials effects of probiotics on estimated glomerular filtration rate and serum creatinine, urea, and Creactive protein remained after multivariate linear regression. There were no significant differences in the urinary parameters between the two groups. Symptoms of constipation (p<0.001) and stool consistency (p=0.016) improved in IG compared to CG. Conclusion: Probiotic supplementation improved markers of renal function and reduced inflammation. In addition, it improved the symptoms of intestinal constipation in patients with CKD.