Le syndrome d'Ehlers-Danlos (SEDv) est une maladie artérielle génétique autosomique dominante, affectant le collagène de type III au sein de la matrice extracellulaire de la paroi artérielle notamment. Les patients atteints de SEDv ont une prédisposition aux ruptures artérielles, digestives et utérines qui font toute la sévérité de cette maladie. Les mutations du gène COL3A1 codant pour le collagène de type III sont le plus souvent des mutations hétérozygotes faux-sens, responsables de la substitution d'une glycine par un autre acide aminé, affectant la structure en triple hélice du collagène de type III. Des variants d'un site d'épissage, des insertions-délétions sont également rencontrées, et plus rarement des mutations faux-sens n'affectant pas une glycine, ou des mutations responsables d'haploinsuffisance. Les mutations du COL3A1 sont presque exclusivement privées, et une corrélation entre le phénotype observé et les mutations retrouvées n'a jamais été mise en évidence. Nous avons rapporté l'expérience du centre de référence français du SEDv sur 215 patients, et retrouvé une sévérité de la maladie plus importante chez ceux avec une substitution glycine, ou une insertion/délétion du cadre de lecture dans région de la triple hélice comparativement aux autres génotypes: variants responsables d'haploinsuffisance, variants faux-sens n'affectant pas une glycine, ou les altérations des extrémités N ou C-terminales. Par ailleurs, le phénotype de ces 3 derniers groupes de génotype ne rassemblait pas l'ensemble des symptômes habituellement décrits dans le SEDv et notamment pas de complication digestive. Afin de mieux comprendre l'altération des propriétés biomécaniques de la paroi artérielle des patients atteints de SEDv nous avons utilisé une nouvelle technologie ultrasonore, ultrafastécho, permettant de visualiser et mesurer la vitesse de l'onde de pouls (VOP) localement au niveau carotidien et tout au long du cycle cardiaque. La VOP est un marqueur de rigidité artérielle bien étudié dans l'athérosclérose, et connu pour être un facteur indépendant de mortalité cardiovasculaire. Nous avons établi des valeurs normales des paramètres de l'ultrafastécho chez 102 volontaires sains et analysés 37 patients avec SEDv. Cette étude n'a pas retrouvé de différence de la VOP, donc de rigidité artérielle, en début de systole. En revanche, au cours du cycle cardiaque on a pu observer une moindre rigidification de la paroi artérielle avec l'augmentation de la pression artérielle chez les patients SEDv. Nous avons poursuivi nos explorations par ultrafastécho sur un modèle murin haploinsuffisant pour le collagène de type III (souris Col3a1 hétérozygote) et retrouvé le même profil de réponse. En effet une moindre augmentation de la rigidité artérielle alors que la pression artérielle était augmentée par perfusion de vasopresseur était constatée chez les souris col3a1 hétérozygotes comparativement aux souris sauvages. En conclusion, l'altération du collagène de type III dans le SEDv affecte les propriétés biomécaniques de la paroi artérielle des patients, avec notamment une moindre rigidification lors de l'augmentation de la pression artérielle. Nos travaux ont permis d’affiner la physiopathologie du SEDv, de préciser le phénotype vasculaire par une nouvelle mesure de la VOP et ouvrent des pistes de recherche thérapeutiques d'un traitement augmentant la rigidité artérielle afin de tenter de réduire les risques de ruptures artérielles. / Vascular Elhers-Danlos syndrome (vEDS) is an autosomal dominant genetic vascular disease, affecting the collagen type III, a component in the extracellular matrix of the arterial wall. Patients with vEDS are prone to arterial, intestine or uterine ruptures, which explain the severity of the disease. Mutations in COL3A1, gene encoding for collagen type III are usually heterozygous missense mutations responsible for the substitution of a glycine amino acid for another, which affects the triple helical conformational structure of the collagen type III. Variants of a splice site, deletions/insertions, are also encountered, and more rarely missense mutations not affecting a glycine residue, or alterations responsible for haploinsufficiency. The COL3A1 mutations are almost exclusively private, and a genotype/phenotype correlation has not been clearly studied. We reported the experience of the French reference center for vEDS of 215 patients and found a greater severity of the disease in those with a glycine substitution, or in frame insertion / deletion within the triple helix domain than in other genotypes: responsible variants of haploinsufficiency, missense variants not affecting glycine, or alteration of the N- or C-terminal ends. Furthermore, the phenotype of these last three genotype groups did not combine the complete phenotype described in vEDS especially no gastrointestinal complication. To better understand the alteration of the biomechanical properties of the arterial wall of patients with vEDS we used a new ultrasound technology, ultrafastecho, to visualize and measure the pulse wave velocity (PWV) locally on carotids, over the cardiac cycle. The PWV is a marker of arterial stiffness studied in atherosclerosis, and well known to be an independent risk factor for cardiovascular mortality. We have established normal values ultrafastecho parameters in 102 healthy volunteers and 37 patients with vEDS. This study found no difference in PWV, thus arterial stiffness, in early systole cardiac at diastolic blood pressure. However, in patients with vEDS, weaker stiffening of the arterial wall was observed when blood pressure increases during the cardiac cycle. We continued our explorations by ultrafastecho on a mouse model of vEDS, haploinsufficient for the collagen type III (Col3a1 heterozygous mice). We figured out that Col3a1 heterozygous mice presented the same response profile. Indeed a smaller increase in arterial stiffness while blood pressure was increasing secondary to vasopressor infusion was revealed in the mice compared to the wild mice. In conclusion, alterations of collagen type III in the vEDS affect the biomechanical properties of the arterial wall of the patient, through lower stiffening during the increase of blood pressure over the cardiac cycle. This provides a therapeutic approach for targeting treatment increasing arterial stiffness in vEDS in order to reduce the risk of arterial rupture.

INTRODUÇÃO: A Hipersensibilidade do seio carotídeo (HSC) é a exacerbação do reflexo normal e foi definida como ocorrência de pausa ventricular 3 segundos ou redução da pressão arterial sistólica (PAS) 50 mmHg em resposta à massagem do seio carotídeo (MSC). Fenômeno relacionado à idade, raramente diagnosticado em pacientes com menos de 50 anos, tem recebido especial atenção como causa de síncope e quedas inexplicadas nos idosos, nas últimas décadas, com relatos de taxas de prevalências superiores a 45%. Entretanto, ainda não estão claras as implicações diagnósticas da HSC na síncope, com resultados controversos na literatura. OBJETIVOS: Determinar a prevalência da HSC em pacientes com sintomas de síncope e pré-síncope e comparar com indivíduos assintomáticos. Correlacionar a resposta à MSC com a rigidez aórtica e os parâmetros anatômicos e funcionais carotídeos. MÉTODOS: Foram avaliados em estudo prospectivo 99 pcts sintomáticos, com síncope ou pré-síncope a esclarecer (idade média de 69 anos, 41,4% homens), e 66 pcts assintomáticos para controle (idade média de 73 anos, 34,8% homens). Excluíram-se pacientes com cardiopatia estrutural ou com contraindicações para MSC. A MSC foi realizada no ponto com maior impulsão carotídea por 5 segundos, com o registro contínuo e não invasivo da pressão arterial (PA) e eletrocardiograma, com o paciente em postura ortostática a 70º. Foram consideradas respostas anormais: cardioinibitória (CI): assistolia 3 segundos e vasodepressora (VD): redução da PAS 50 mmHg. O índice da rigidez arterial foi obtido por meio de medida da velocidade de onda de pulso carotídeo-femoral (VOP). As características anatômicas e funcionais da carótida foram determinadas por medidas de diâmetro, espessura íntima-média carotídea (EIMC) e índice de distensibilidade. RESULTADOS: Não foram constatadas diferenças nas respostas obtidas na MSC entre os grupos, com 67,7% e 60,6% de respostas fisiológicas; 24,2% e 25,8% de respostas CI; 8,1% e 13,6% de respostas VD em grupo sintomáticos e assintomáticos, respectivamente (p=0,466). Não foram observadas correlações entre a resposta à MSC, tanto com a VOP como com a EMIC, a distensibilidade e o diâmetro carotídeo. CONCLUSÕES: 1- A prevalência de HSC e resposta hemodinâmica à MSC em pacientes com sintomas de síncope e pré-síncope foram semelhantes a pacientes assintomáticos provenientes da mesma instituição, com características clínicas semelhantes. 2- Não foi observada correlação significativa entre a rigidez arterial, medida por meio da VOP, EIMC, distensibilidade e diâmetro carotídeo e a resposta à MSC / The carotid sinus hypersensitivity (CSH) is the exaggeration of the normal reflex and was defined by occurrence of asystole 3 seconds or fall in systolic BP 50 mmHg in response to carotid sinus massage (CSM). Phenomenon related to age, rarely diagnosed in patients younger than 50 years, has gained importance as a cause of syncope and unexplained falls in the elderly in recent decades with reported prevalence rates above 45%. However, the correlation between CSH and syncope etiology is still controversial. OBJECTIVE: To determine the prevalence of CSH in patients with syncope and near syncope of unknown origin and compare with asymptomatic individuals; to evaluate the correlation between CSM responses and arterial stiffness. METHODS: We studied prospectively 99 symptomatic pts with syncope or near syncope (mean age 69 years, 41.4% men) and 66 asymptomatic controls (mean age 73 years, 34.8% men). Patients with significant structural heart disease or with contraindications to CSM were excluded. The CSM was performed at the point with maximal carotid pulsation, for 5 seconds with continuous and noninvasive blood pressure and electrocardiogram recording at 70° in upright posture. Were considered abnormal responses: cardioinhibitory (CI): asystole 3 seconds and vasodepressor (VD): decrease in systolic BP 50 mmHg. The aortic stiffness was determined by aortic pulse wave velocity (PWV). The anatomical and functional characteristics of the carotid were determined by measurements of diameter, intima-media thickness (IMT) and distensibility index. RESULTS: There were no differences in the responses obtained in the CSM between the groups, being 67.7 % and 60.6% physiological responses, 24.2% and 25.8% CI responses and 8.1% and 13.6% VD responses in symptomatic and asymptomatic groups, respectively (p=0.466). There were no correlations between response to the CSM with VOP, IMT, carotid diameter and distensibility. CONCLUSIONS: The prevalence of CSH in patients with symptoms of syncope and near syncope was similar to asymptomatic patients from the same institution with similar clinical characteristics. There was no significant correlation between arterial stiffness, measured by PWV, IMT, carotid diameter and distensibility with the response to CSM

A Arterite de Takayasu (AT) é uma vasculite granulomatosa de aorta e grandes vasos associada a elevado risco cardiovascular. A velocidade de onda de pulso (VOP) é um método de avaliação indireta de diminuição da distensibilidade arterial, e valores elevados de VOP correlacionam-se com maior morbimortalidade cardiovascular. A avaliação da VOP em pacientes com arterite de Takayasu é complexa devido a muitos fatores de confusão. O objetivo do presente estudo foi avaliar a rigidez arterial, por meio da velocidade de onda de pulso carótido-femoral (VOP-CF) em pacientes do sexo feminino com arterite de Takayasu e controles saudáveis com variáveis clínicas e antropométricas comparáveis, e sua possível associação com os parâmetros da doença. Método: Pacientes com arterite de Takayasu (n = 27) foram avaliados consecutivamente e foram selecionados controles saudáveis com idade, pressão arterial, peso e altura comparáveis (n = 27). Os critérios de exclusão foram menopausa, tabagismo, diabetes, insuficiência renal, hipertensão mal controlada, arritmias cardíacas, obesidade, comorbidades inflamatórias, gravidez e história de procedimentos cirúrgicos que envolvessem a aorta. A atividade da doença foi determinada por parâmetros clínicos e laboratoriais. As medições de VOP-CF foram obtidas pelo Sistema Complior. Resultados: A média de VOP-CF foi maior em pacientes com arterite de Takayasu do que em controles (9,77 ± 3,49 vs. 7,83 ± 1.06 m/s, p = 0,009). Apesar dos rigorosos xv critérios de seleção, os pacientes com arterite de Takayasu ainda apresentavam, em média, pressão arterial sistólica de 8 mmHg maior do que os controles (p > 0,05), e os valores de pressão de pulso significativamente mais elevados. O modelo de regressão linear múltipla mostra que 93,8% da variabilidade da VOP é explicada pelas variáveis idade, pressão arterial média (PAM) e pela própria doença (R2 ajustado = 0,938). A análise logística stepwise usando como variável dependente o valor de corte de VOP estabelecido pela curva ROC (> 8,34 m/s) e, como variáveis independentes, os parâmetros com significância na análise univariada, revelou que arterite de Takayasu (OR: 4,69, IC 95% 1,31 - 16,72; p = 0,017) e PAM (OR: 1,06, IC 95% 1,00 - 1,12, p = 0,048) foram independentemente associados a maior VOP. Uma análise mais aprofundada dos parâmetros de doença revelou que os valores de VOP não foram correlacionados com velocidade de hemossedimentação, proteína C-reativa, dose cumulativa de glicocorticoides e fração de ejeção (p > 0,05). Conclusão: Nesta coorte de pacientes do sexo feminino com arterite de Takayasu, a própria doença e a pressão arterial média foram os determinantes mais fortemente associados com elevada rigidez arterial e não houve correlação dos valores de VOP com parâmetros de atividade da doença / Takayasu arteritis (TA) is a granulomatous vasculitis that affects the aorta and large vessels and is associated with higher cardiovascular risk. Pulse wave velocity (PWV) is a method of indirect evaluation of decreased arterial distensibility, and elevated PWV correlates with increased cardiovascular morbidity and mortality. The assessment of PWV in patients with Takayasu arteritis is complex due to many confounding factors. The aim of this study was to evaluate arterial stiffness, assessed by carotid-femoral pulse wave velocity (CF-PWV) in female patients with TA and healthy controls with comparable anthropometric and clinical variables, and the possible association with parameters of the disease. Method: Patients with TA (n = 27) were consecutively evaluated and healthy controls were selected with comparable age, blood pressure, weight and height (n = 27). Exclusion criteria were menopause, smoking, diabetes, renal insufficiency, poorly controlled hypertension, cardiac arrhythmias, obesity, inflammatory comorbidities, pregnancy and history of surgical procedures involving the aorta. Disease activity was determined by clinical and laboratory parameters. The CF-PWV measurements were obtained by the Complior System. Results: The mean CF-PWV was higher in patients with TA than in controls (9.77 ± 3.49 vs. 7.83 ± 6.1 m / s, p = 0.009). Despite the strict selection criteria, TA patients still had, on average, systolic blood pressure of 8 mmHg greater than controls (p > 0.05), and pulse pressure values significantly higher. The multiple linear regression model showed that 93.8% of the variability in PWV is explained by the variables age, mean arterial pressure (MAP) and the disease itself (adjusted R2 = 0.938). A stepwise logistic analysis using as the dependent variable the cutoff value of VOP established by the ROC curve (> 8.34 m/s) and, as independent variables, parameters with significance in the univariate analysis, revealed that Takayasu arteritis (OR: 4.69 95% CI 1.31 - 16.72, p = 0.017) and MAP (OR: 1.06, 95% CI 1.00 - 1.12, p = 0.048) were independently associated with increased PWV. Further analysis of disease parameters revealed that PWV values were not correlated with erythrocyte sedimentation rate, C-reactive protein, cumulative dose of glucocorticoids or ejection fraction (p > 0.05). Conclusion: In this cohort of female patients with Takayasu arteritis, the disease itself and mean arterial pressure were determinants most strongly associated with elevated arterial stiffness and no correlation of PWV values and parameters of disease activity was found

<p>Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors.</p><p>We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors.</p><p>Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels.</p><p>In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change.</p><p>In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels.</p><p>These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.</p>

Kidney dysfunction increases cardiovascular disease (CVD) risk. The mechanisms for the risk increase seem to involve a combination of traditional and non-traditional CVD risk factors. We studied renal dysfunction as CVD and mortality risk factor in middle-aged men free from diabetes and CVD. The risk for myocardial infarction (MI) and CVD mortality was increased by ~40% in the 16.5% of men with worse renal function, independent of other CVD risk factors. Renal transplant dysfunction as CVD and mortality risk factor was also studied. Renal transplant dysfunction was a risk factor for mortality and for combined CVD endpoint. The risk by renal transplant dysfunction was independent of traditional CVD risk factors as well as transplantation-specific risk factors. Only moderate increase in serum creatinine resulted in mortality and CVD risk comparable to diabetes, older age and higher low density lipoprotein levels. In haemodialysis patients, the effects of a dialysis session on non-traditional CVD risk factors were studied. A HD session reduced asymmetric dimethylarginine (ADMA) and homocysteine levels, as well as augmentation index (AIx). The change in AIx was related to ADMA plasma level change. In patients with stage 3-5 chronic kidney disease (CKD), endothelium dependent vasodilation (EDV) was studied together with markers of oxidative stress and C-reactive protein (CRP). CRP was related to lipid peroxidation, while EDV was related to intracellular antioxidative capacity measured by reduced glutathione levels. These studies demonstrate that mild to moderate renal dysfunction is independently associated with increased CVD risk in apparently healthy people, as well as in renal transplant recipients. The mechanisms by which renal dysfunction increases CVD risk are yet to be elucidated. We suggest that arterial stiffness could be reduced in haemodialysis patients by increasing nitric oxide bioavailability. In stage 3-5 CKD patients, improving intracellular antioxidative capacity may result in endothelial function improvement.

African Americans have increased risk for cardiovascular and cerebral vascular disease relative to Caucasian Americans. While it is generally accepted that arteries become stiffer at a younger age in African Americans; less is known regarding cerebral vascular function / reactivity (CVMR) to hypercapnia in African Americans. Furthermore, little is known regarding the relationship between arterial stiffness and CVMR, particularly in young healthy adults. We hypothesized that African Americans have stiffer arteries (i.e. arterial stiffness) and reduced CVMR during hypercapnia relative to Caucasian Americans. We also hypothesized that there would be a negative relationship between arterial stiffness and CVMR. Lastly, we hypothesized that these responses would be related to a decrease in Vitamin D status in this population and there would be correlation between Vitamin D status and CVMR. In 11 African American and 19 Caucasian American subjects central arterial stiffness was indexed from carotid-femoral pulse wave velocity (PWV). CVMR was assessed by the cerebral vascular conductance (CVC) response to rebreathing-induced hypercapnia. Vitamin D status was assessed from plasma 25(OH) Vitamin D. PWV was elevated in the African Americans (African American: 581.16 ± 27.7 cm/sec vs. Caucasian American: 502.98 ± 17.6 cm/sec; P < 0.01). CVMR was significantly reduced during hypercapnic rebreathing in the African Americans (African American: 3.05 ± 0.38% of baseline/mmHg vs. Caucasian American: 5.09 ± 0.29% of baseline/mmHg; P < 0.001). When data from all subjects was included there was a trend towards a negative relationship (R = 0.32, P = 0.10) between PWV and CVMR. Vitamin D status was significantly lower in African Americans (African American: 14.96 ± 0.97 ng/ml vs. Caucasian American: 32.73 ± 0.99 ng/ml; P < 0.001); however, there was no significant relationship between Vitamin D status and CVMR (R = 0.23 P = 0.23). In conclusion, these data indicate that African Americans have impaired cerebral vascular responses to hypercapnia, stiffer arteries, and lower Vitamin D status when compared with Caucasian Americans. In addition, there may be a negative relationship between CVMR and PWV; however, no significant correlation between Vitamin D status and vascular function including PWV or CVMR was observed in this study. / text

Several research studies indicate the increasing problem obesity has become over the past few decades (Andersen 1999:41; Fox, 1999:56-60; Kuczmarshi et al., 1994:205-212). Obesity, after cigarette smoke, is the leading cause of death in the USA and a combination of diet factors and physical inactivity (two primary contributors of obesity) leads to an average of 300,000 deaths per year (McGinnis & Foege, 1993:2207-2212). Previously little information was available on the effect of obesity on the peripheral vascularization, and even less about the effect of obesity on arterial compliance (Raison et al., 1998:299-303). Research indicated a decrease in arterial compliance with an increase in body weight (Kumaran et al., 2002:7; Sutton-Tyrrell et al., 2001:431; Tounian et al., 2001:1400-1404; Stepniakowski & Egan, 1995:R567) however, contradictory research where no association between obesity and arterial compliance was indicated, has also been found (Singhal et al., 2002:1920; Mangoni et al., 1995:986). Mackey et al. (2002:16) also found that an increased aortic stiffness is positively associated with lowered physical activity levels. A lifestyle consisting of moderate physical activity, has a positive effect on the health, lowering of chronic illness risks, the prevention of cardiovascular diseases and the improvement of quality of lie in overweight and obese patients (Adams et al., 2003542; Ferreira et al., 2003:1670-1678; Macera, 2003:123; Mclnnis, 200396; Kolden et al., 2002:447). Moderate aerobic exercise is also seen as a potential non-pharmaceutical therapeutic method to increase age associated decrease in arterial compliance in young, middle aged and older adults (Gates et al., 2003:2213; Havlik et al., 2003:156; Seals, 2003:68; Moreau et al., 2003:865; Joyner, 2000:1214; Cameron et al., 1999:653). The objective of this study was firstly to determine the correlation between obesity and vascular function in Caucasian women between the ages 19 and 56 and to determine which marker of obesity is the best predictor of a weakened vascular function (see article one). The second objective was to determine the correlation between physical activity, obesity and arterial compliance in Caucasian women between the ages 19 and 56 years (see article 2). A total of 115 Caucasian women were recruited to participate in this study. Anthropometric measurements and a comprehensive body composition profile was taken using the BOD POD. The Finometer apparatus was used to measure the arterial compliance and the sphygmomanometer to measure the subjects blood pressure. The subjects completed the Yale Physical Activity Survey questionnaire to determine their physical activity index. This study seems to indicate a positive relationship between arterial compliance and obesity which could be explained by the influence blood volume had in determining arterial compliance. A negative correlation was found between obesity and blood pressure where an increase in obesity caused an increase in both systolic and diastolic blood pressure. A positive correlation was found between physical activity and obesity. The higher the activity levels were in this study, the less obese the subjects tended to be. No correlation was found between physical activity and arterial compliance. A clear trend, even though no statistically significant differences, was found between physical activity and blood pressure. The more active the subjects were, the lower their blood pressure tended to be. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2005

Several research studies indicate the increasing problem obesity has become over the past few decades (Andersen 1999:41; Fox, 1999:56-60; Kuczmarshi et al., 1994:205-212). Obesity, after cigarette smoke, is the leading cause of death in the USA and a combination of diet factors and physical inactivity (two primary contributors of obesity) leads to an average of 300,000 deaths per year (McGinnis & Foege, 1993:2207-2212). Previously little information was available on the effect of obesity on the peripheral vascularization, and even less about the effect of obesity on arterial compliance (Raison et al., 1998:299-303). Research indicated a decrease in arterial compliance with an increase in body weight (Kumaran et al., 2002:7; Sutton-Tyrrell et al., 2001:431; Tounian et al., 2001:1400-1404; Stepniakowski & Egan, 1995:R567) however, contradictory research where no association between obesity and arterial compliance was indicated, has also been found (Singhal et al., 2002:1920; Mangoni et al., 1995:986). Mackey et al. (2002:16) also found that an increased aortic stiffness is positively associated with lowered physical activity levels. A lifestyle consisting of moderate physical activity, has a positive effect on the health, lowering of chronic illness risks, the prevention of cardiovascular diseases and the improvement of quality of lie in overweight and obese patients (Adams et al., 2003542; Ferreira et al., 2003:1670-1678; Macera, 2003:123; Mclnnis, 200396; Kolden et al., 2002:447). Moderate aerobic exercise is also seen as a potential non-pharmaceutical therapeutic method to increase age associated decrease in arterial compliance in young, middle aged and older adults (Gates et al., 2003:2213; Havlik et al., 2003:156; Seals, 2003:68; Moreau et al., 2003:865; Joyner, 2000:1214; Cameron et al., 1999:653). The objective of this study was firstly to determine the correlation between obesity and vascular function in Caucasian women between the ages 19 and 56 and to determine which marker of obesity is the best predictor of a weakened vascular function (see article one). The second objective was to determine the correlation between physical activity, obesity and arterial compliance in Caucasian women between the ages 19 and 56 years (see article 2). A total of 115 Caucasian women were recruited to participate in this study. Anthropometric measurements and a comprehensive body composition profile was taken using the BOD POD. The Finometer apparatus was used to measure the arterial compliance and the sphygmomanometer to measure the subjects blood pressure. The subjects completed the Yale Physical Activity Survey questionnaire to determine their physical activity index. This study seems to indicate a positive relationship between arterial compliance and obesity which could be explained by the influence blood volume had in determining arterial compliance. A negative correlation was found between obesity and blood pressure where an increase in obesity caused an increase in both systolic and diastolic blood pressure. A positive correlation was found between physical activity and obesity. The higher the activity levels were in this study, the less obese the subjects tended to be. No correlation was found between physical activity and arterial compliance. A clear trend, even though no statistically significant differences, was found between physical activity and blood pressure. The more active the subjects were, the lower their blood pressure tended to be. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2005

La rigidité artérielle est considérée comme un facteur de risque important pour le développement du déclin cognitif. Toutefois, les effets précis de la rigidité artérielle sur le cerveau sont peu connus et, à ce jour, aucun modèle animal ne permet d’étudier l’effet isolé de ce facteur sur l’homéostasie cérébrale. Dans cette étude, nous avons développé un nouveau modèle de rigidité artérielle qui se base sur la calcification de l’artère carotide chez la souris. Au niveau artériel, ce modèle présente une fragmentation de l’élastine, une augmentation de la distribution du collagène et de l’épaisseur intima-média ainsi qu’une diminution de la compliance et de la distensibilité artérielles démontrant la rigidité artérielle. De plus, le modèle ne présente pas d’augmentation de pression artérielle ni de changement de rayon du lumen indiquant une absence d’hypoperfusion globale et d’anévrisme. Au niveau cérébral, les résultats montrent que la rigidité artérielle induit une augmentation de la pulsatilité du flux sanguin cérébral menant ainsi à une augmentation du stress oxydatif. Ce dernier induit une inflammation cérébrale, détectée par l’activation de la microglie et des astrocytes, induisant ultimement une neurodégénérescence. Ces effets sont surtout observés au niveau de l’hippocampe, la région cruciale pour la mémoire et la cognition. Ainsi, cette étude montre que la rigidité artérielle altère l’homéostasie cérébrale et mérite d’être considérée comme une cible potentielle dans la prévention et le traitement des dysfonctions cognitives chez les personnes âgées. / Arterial stiffness is considered as an important risk factor for the development of cognitive decline in the elderly population. However, its precise effects on the brain are unknown and, to date, no animal model allows to study the precise outcome of arterial stiffness on the brain homeostasis. In this study, we developed a new animal model of arterial stiffness based on the calcification of the carotid artery in mice. On the arterial level, this model shows a fragmentation of elastin, increased collagen distribution and intima-media thickness as well as decreased arterial compliance and distensibility, thus fulfilling the major arterial stiffness properties. In addition, this model does not a show an increase in blood pressure or change in arterial lumen radius indicating a lack of global hypoperfusion and aneurysm. Regarding the brain, the results show that arterial stiffness induces an increase in cerebral blood flow pulsatility leading to increased oxidative stress. Oxidative stress induces brain inflammation, detected by the activation of microglia and astrocytes, ultimately leading to neurodegeneration. These effects are particularly observed in the hippocampus, a crucial area for memory and cognition. Thus, this study shows that arterial stiffness alters brain homeostasis and therefore should be considered as a potential therapeutical target for the prevention and treatment of cognitive dysfunction in the elderly.

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No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) tese_6422_2011_Milena Batista Santos.pdf: 4504155 bytes, checksum: 2e5a0bc2576eeeb83dab522c8a5772df (MD5) / Há evidências de que fatores de risco para ocorrência de Doenças Crônicas não Transmissíveis têm início silencioso em etapas precoces do desenvolvimento. Essa questão foi suscitada a partir de estudos que relacionaram o peso ao nascer com o desenvolvimento de doenças na vida adulta, cuja hipótese se baseia na ideia de que o feto seria programado intra-útero, principalmente por fatores nutricionais que influenciariam no metabolismo e na fisiologia do indivíduo por toda a vida. O objetivo deste estudo foi investigar a saúde cardiovascular de crianças de 9 a 10 anos e sua relação com as condições de nascimento (baixo peso ao nascer e prematuridade) e de amamentação. Foram avaliadas 231 crianças, de ambos os sexos, matriculadas em escolas públicas e privadas do município de Vitória/ES. As crianças compareceram em jejum, acompanhadas de seus responsáveis, no Centro de Investigação Cardiovascular da UFES para realização de exames antropométricos, laboratoriais e hemodinâmicos (pressão arterial e velocidade de onda de pulso carótida-femoral - VOP). No dia da visita, as crianças e seus responsáveis responderam a um questionário sobre questões de saúde atuais e pregressas. O teste Kolmogorov-Smirnov foi utilizado para testar a normalidade das variáveis contínuas e depois realizados os testes t de Student para amostras independentes ou Mann Whitney. O teste do qui-quadrado (X2) foi utilizado para avaliar a distribuição das variáveis categóricas. Variáveis hemodinâmicas, categorizadas em tercis, foram analisadas utilizando ANOVA a uma via, seguida do teste de Tukey para avaliação entre grupos. Variáveis contínuas foram correlacionadas utilizando teste de Pearson ou de Spearman. Aplicou-se a análise de regressão linear múltipla para identificar a contribuição parcial e total dos fatores na determinação dos valores de VOP e de pressão arterial. O nível de significância estabelecido para todos os testes foi de =0,05. Observou-se maior frequência de meninos nas classes socioeconômicas A+B (61%) e na condição de sobrepeso (meninas= 38%, meninos= 51%, p=0,05). O baixo peso ao nascer foi mais frequente entre meninas (meninas=18%, meninos=7%, p=0,01). Crianças do sexo masculino apresentaram maiores médias de PAS (p=0,05), VOP (p=0,03) e peso ao nascer (p<0,01), quando comparados às meninas. A PAS foi maior entre as crianças nascidas com peso igual ou superior a 2500g. Não foi encontrada diferença estatística das médias de PAD e VOP e peso ao nascer. A prematuridade e amamentação também não foram associadas aos níveis pressóricos e à rigidez arterial. O IMC apresentou associação positiva e significativa com PAS, PAD e VOP. A análise de regressão linear indicou que 44% do aumento da PAS nas crianças avaliadas são explicados pelo IMC. Para a PAD as variáveis que se mantiveram no modelo foram o IMC e VOP, explicando 38% nas alterações de PAD. Os fatores que explicaram as alterações na VOP foram IMC e PAD (r=0,29; p<0,01). Conclui-se que a hipótese de programação fetal e infantil não foi comprovada neste estudo e que apenas o IMC foi associado ao aumento da PAS, da PAD e da VOP, após ajuste por sexo. / There are evidences that risk factors for the occurrence of Chronic Non-Communicable diseases begin silently in early stages of development. This question was raised from studies related to birth weight in the development of diseases in adulthood, whose hypothesis is based on the idea that the fetus would be programmed in utero, mainly nutritional factors that influence the metabolism and physiology the individual throughout life. The objective of this research was investigate the cardiovascular health of children 9-10 years and their relation to perinatal conditions (low birth weight and prematurity) and breastfeeding. We evaluated 231 children of both sexes enrolled in public and private schools of the city of Vitória / ES. The children attended fasting, were accompanied by their guardians to the Cardiovascular Research Center of UFES for exams anthropometric, laboratory and hemodynamic (blood pressure and pulse wave velocity carotid-femoral). On the day of the visit, children and their parents completed a questionnaire on health issues, and were instructed to collect the urine of 12 hours night. The Kolmogorov-Smirnov test was used to test the normality of continuous variables and then performed the Student t test for independent samples or Mann Whitney. The chi-square (X2) was used to assess the distribution of categorical variables. Hemodynamic variables, categorized into tertiles were analyzed using ANOVA to a route followed by the Tukey test to evaluate between groups. Continuous variables were correlated using Pearson or Spearman. We applied the multiple linear regression analysis to identify the contribution partial and total factor in determining values of PWV and blood pressure. The significance level for all tests was set at α = 0.05. There was a higher frequency in boys socioeconomic classes A + B (61%) and overweight status (girls = 38%, boys = 51%, p = 0.05). The low birth weight was more common among girls (girls = 18%, boys = 7%, p = 0.01). Male children had higher mean SBP (p = 0.05), PWV (p = 0.03) and birth weight (p <0.01) when compared to girls. SBP was higher among infants born weighing less than 2500g. There was no statistical difference of mean DBP and PWV and birth weight. Preterm birth and breastfeeding were not associated with blood pressure and arterial stiffness. BMI showed significant positive association with increased SBP, DBP and PWV. Linear regression analysis indicated that 44% of the increase of SBP in children evaluated are explained by BMI. For DBP the variables that remained in the model were BMI and PWV changes in explaining 38% of PAD. Factors that explained the changes in PWV were BMI and DBP (0.29, p <0.01). We conclude that the hypothesis of fetal programming and child was not proven in this study and that only BMI was associated with increased SBP, DBP and PWV after adjustment for sex.