Introdução: A Apneia obstrutiva do sono (AOS) é uma doença comum na população geral e sua presença pode ser parcialmente explicada por um componente genético. No entanto, existe uma interação grande entre AOS com fatores de confusão, incluindo obesidade. O objetivo principal desse estudo é determinar a herdabilidade da AOS em uma população rural brasileira. Métodos: Foram estudados famílias provenientes de coorte (Corações de Baependi). Os participantes foram avaliados quanto a medidas antropométricas, circunferência de cintura, quadril e pescoço. Aplicamos os questionários de Berlim para determinar o risco de ter AOS, escala de sonolência de Epworth para verificar sonolência excessiva diurna e o questionário de Pittsburgh para verificar a qualidade do sono. Realizamos poligrafia noturna para determinar a presença e gravidade da AOS utilizando o índice de apneia-hipopneia (IAH, definido positivo quando >= 15 eventos/hora). Foi realizada medida de pressão arterial (PA) por meio da monitorização ambulatorial da pressão arterial (MAPA) e velocidade de onda de pulso (VOP) para avaliar rigidez arterial. Resultados: A amostra foi composta de 587 participantes (188 homens e 399 mulheres), com mediana de idade e intervalo interquartil = 44 (29 - 55) anos e IMC = 25,0 (22,1-28,6) kg/m2. Os sintomas sugestivos de AOS derivados dos questionários de Epworth, Berlim e Pittsburgh não se associaram com a presença de AOS; A AOS foi diagnosticada em 18,6% eventos/hora da população, A herdabilidade foi estimada em 26%, independente da obesidade e outros fatores de confusão. A mediana da PA foi mais alta, a ausência de descenso noturno da PA foi mais comum e o VOP mais alto em participantes com AOS do que sem AOS. Na regressão logística multivariada apenas a idade e a PA se associaram de forma significante com o VOP. Conclusões: A herdabilidade da AOS foi moderada (26%) em uma população rural. As alterações cardiovasculares presentes na AOS estão associadas a fatores de confusão em estudos familiares / Introduction: Obstructive sleep apnea (OSA) is a common disease in the general population and the presence can be partially explained by a genetic component. However, there is a strong interaction between OSA with confounding factors, including obesity. The main objective of this study is to determine the heritability of OSA in a Brazilian rural population. Methods: We studied families from the Baependi Heart Study. Participants were assessed for anthropometric measurements, waist, hip and neck circumferences. We used the Berlin questionnaire to determine the risk of having OSA, Epworth sleepiness scale to evaluated the presence of excessive daytime sleepiness and the questionnaire of Pittsburgh to verify the quality of sleep. Overnight Polygraph night was conducted to determine the presence and severity of OSA through the apnea-hypopnea index. Blood pressure was measured (BP) by ambulatory blood pressure (ABP) and pulse wave velocity (PWV) to assess arterial stiffness. Results: The sample consisted of 587 participants (188 men and 399 women), median and interquartile range of age = 44 (29-55) years and BMI = 25.0 (22.1 to 28.6) kg / m2. Symptoms suggestive of OSA derived from Epworth, Berlin and Pittsburgh questionnaires were not associated with the presence of OSA; OSA was diagnosed in 18.6% events/hour of the population, the heritability was estimated at 26%, independent of obesity and other confounding factors. BP was higher, the absence of nocturnal BP was more common and the highest VOP in participants with OSA than without OSA. Using multivariate logistic regression only age and BP were associated significantly with PWV. Conclusions: OSA heritability is moderate (26%) in a rural population. The cardiovascular alterations associated with OSA were explained by confounding factors

Introdução: A apneia obstrutiva do sono (AOS) é uma condição clínica comum associada com o aumento do risco cardiovascular. No entanto, a maioria dos estudos envolvendo AOS e desfechos cardiovasculares recrutaram de forma preponderante os homens. Em pacientes hipertensos, a AOS pode contribuir para a lesão de órgãos-alvo e alterações no descenso noturno em homens. O impacto da AOS nas mulheres hipertensas é pouco estudado. O objetivo deste estudo é estudar o impacto da AOS na rigidez arterial da aorta (avaliada pela velocidade da onda de pulso, VOP, carótida-femoral), disfunção diastólica e alterações do descenso noturno da pressão arterial em ambos os gêneros. Fazemos a hipótese de que a AOS está associada com alterações na rigidez arterial, disfunção diastólica e comportamento da pressão arterial independente do gênero. Métodos: Recrutamos de forma consecutiva pacientes hipertensos estágio 2 do ambulatório de Hipertensão do Instituto do Coração. Padronizamos a medicação anti-hipertensiva (hidroclorotiazida 25mg ao dia e enalapril 20mg 2x ao dia ou losartan 50mg 2x ao dia em caso de intolerância ao enalapril) por 1 mês. A adesão do tratamento aconteceu por meio da contagem de pílulas. Foram realizadas avaliações da monitorização ambulatorial da pressão arterial (MAPA), VOP, ecocardiograma transtorácico, exames laboratoriais e a Polissonografia Noturna. A AOS foi diagnosticada por um índice de apneia e hipopneia >= 15 eventos por hora de sono. Resultados: Foram inicialmente recrutados 125 participantes e após as exclusões, avaliamos 95 pacientes hipertensos (56% mulheres). A frequência da AOS foi de 66,7% em homens e 45,3% em mulheres (p=0,02). Em relação às mulheres sem AOS, mulheres com AOS eram mais velhas, tinham maior índice de massa corpórea e apresentaram maiores circunferências cervical e abdominal. Os homens com e sem a AOS foram semelhantes em várias características, exceto por uma circunferência abdominal maior no grupo com AOS. Comparado aos pacientes sem AOS, a VOP foi estatisticamente maior nos homens portadores de AOS (11,1±2,2 vs. 12,7±2,4m/s, respectivamente; p=0,04), assim como nas mulheres (11,8±2,4 vs. 13,2±2,2m/s, respectivamente; p=0,03). Em relação à disfunção diastólica, apenas as mulheres com AOS mostraram maior porcentagem dessa alteração ecocardiográfica (46,1 vs. 81,8%, respectivamente; p=0,007). Foi visto nos resultados da MAPA, que homens com AOS apresentaram menor frequência do descenso noturno sistólico (46,4 vs. 14,3%, respectivamente; p=0,04) e as mulheres, uma tendência (65,2 vs. 41,4%; p=0,07). O resultado da regressão linear mostrou que a presença de AOS promove aumento independente nos valores da VOP. O resultado da regressão logística evidenciou que a presença da AOS não foi associada com a disfunção diastólica, mas foi com a ausência do descenso noturno do componente sistólico da pressão arterial. Conclusões: Em pacientes hipertensos, a presença da AOS foi associada com um aumento na rigidez arterial independente do sexo, assim como a ausência do descenso noturno do componente sistólico da pressão arterial. Estes dados sugerem que mulheres hipertensas também estão expostas às consequências vasculares da AOS / Introduction: Obstructive sleep apnea (OSA) is a common condition associated with increased cardiovascular risk. However, most of studies that addressed OSA and its cardiovascular consequences enrolled mainly men. In hypertensive patients, OSA may contribute to increased target organ damage and alterations in the blood pressure dipping in males. However, the impact of OSA in hypertensive females is not well established. In this study, we compared the impact of OSA on arterial stiffness of the aorta (evaluated by carotid-femoral pulse wave velocity, PWV), as well as diastolic dysfunction and blood pressure dipping in men and women with hypertension. We made the hypothesis that OSA is associated with higher arterial stiffness, higher frequency of diastolic dysfunction and impaired blood pressure behavior regardless of gender. Methods: We recruited consecutives stage 2 hypertensive patients from the outpatient clinic at the Heart Institute. We performed a 30-day standardized anti-hypertensive treatment with hydrochlorothiazide 25mg per day plus enalapril 20mg BID or losartan 50mg BID (if enalapril intolerance). Adherence to treatment was confirmed through pill counting. After that, all volunteers were submitted to clinical evaluation, carotid-femoral PWV, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiogram, and polysomnography. OSA was defined by an apnea-hypopnea index >= 15 events per hour. Results: We initially recruited 125 participants and after exclusions ninety-five patients were studied (56% women). OSA was present in 52 patients (men: 66.7%; women: 45.3%; p=0.02). In comparison to women without OSA, women with OSA were older, had higher body mass index and higher neck and abdominal circumferences. In men, there were no differences between OSA and no-OSA groups, except for higher values of abdominal circumference in OSA patients. Compared to no-OSA patients, PWV values were higher in the OSA group among both males (11.1±2.2 vs. 12.7±2.4m/s, respectively; p=0.04) and females (11.8±2.4 vs. 13.2±2.2m/s, respectively; p=0.03). The impact of OSA on diastolic dysfunction was significant only in females (46.1 vs. 81.8%, respectively; p=0.007). Regarding ambulatory blood pressure monitoring data, the frequency of systolic blood pressure dipping was significantly lower in men with OSA (46.4 vs. 14.3%, respectively; p=0.04) and marginal but non-significant in women (65.2 vs. 41.4%; p=0.07). Linear regression analysis showed that the presence of OSA was independently associated with higher PWV. In the logistic regression analysis, OSA was not associated with diastolic dysfunction but independently associated with nondipping systolic blood pressure. Conclusion: In patients with hypertension, OSA has significant associated with higher arterial stiffness and nondipping systolic blood pressure regardless of gender. These data suggest that hypertensive women are also exposed to the vascular and hemodynamic consequences of OSA

Elle peut être estimée par deux indices : la distensibilité de la paroi aortique et la vitessede propagation de l'onde de pouls (VOP) le long de l'artère. Ces marqueurs peuvent êtreobtenus dans l'aorte proximale grâce à l'imagerie de résonance magnétique (IRM) et sontreliés entre eux par le modèle de Bramwell-Hill. L'objectif de cette thèse est, d'une part, deproposer et de valider cliniquement des méthodes d'estimation de la distensibilité et de laVOP aortique, et, d'autre part, d'étudier le modèle théorique de Bramwell-Hill, au regarddes données cliniques. Nous avons dans un premier temps comparé différentes méthodesd'estimation de la distensibilité de l'aorte. Cette étude a permis d'identifier l'approche quifournit la meilleure description physiologique de l'aorte ascendante et descendante. Ensuite,nous avons proposé une nouvelle méthode de mesure de la VOP proximale. Celle-cia été validée par comparaison avec les méthodes proposées dans la littérature en termesde reproductibilité et de corrélations des mesures avec : 1) l'âge : facteur de risque "naturel " de la rigidité aortique chez des sujets sains, et 2) la VOP carotido-fémoralemesurée par tonométrie, méthode de référence utilisée en routine clinique pour estimer larigidité globale de l'aorte. Enfin, nous avons validé le modèle théorique de Bramwell-Hillau niveau des sections de l'aorte ascendante et descendante. En conclusion, nous avonsproposé des approches locale et régionale d'évaluation de la rigidité de l'aorte proximaleet nous en avons validé la robustesse, notamment dans le cadre du vieillissement artériel. / The aortic stiffness is recognized as a major factor of cardiovascular risk, and is characterizedby distensibility and pulse wave velocity (PWV) measurements. These aorticindices are related according to the Bramwell-Hill model and can be assessed in the proximalaorta with magnetic resonance imaging (MRI). The aims of this thesis were : 1) topropose and validate clinical methods for estimating the distensibility and aortic PWVfrom MRI data, and 2) to study the theoretical model of Bramwell-Hill in the light ofclinical data. First, we compared different methods for estimating the distensibility ofthe aorta. This study permitted to identify the approach which provides the best physiologicaldescription of the ascending and descending aorta. Then we proposed a newmethod for estimating the PWV in the proximal aorta, which was validated by comparisonwith previously described methods in terms of reproducibility and correlation ofaortic PWV with : 1) age : major risk factor of aortic stiffness in healthy subjects, and 2)carotid-femoral PWV measured by tonometry, gold standard method in clinical routinefor estimating the overall stiffness of the aorta. Finally, we validated the theoretical modelof Bramwell-Hill at the sections of the ascending and descending aorta. In conclusion, weproposed local and regional approaches to assess the stiffness of the proximal aorta, andwe validated its robustness, particularly in the context of aging.

Introdução: A Apneia obstrutiva do sono (AOS) é uma doença comum na população geral e sua presença pode ser parcialmente explicada por um componente genético. No entanto, existe uma interação grande entre AOS com fatores de confusão, incluindo obesidade. O objetivo principal desse estudo é determinar a herdabilidade da AOS em uma população rural brasileira. Métodos: Foram estudados famílias provenientes de coorte (Corações de Baependi). Os participantes foram avaliados quanto a medidas antropométricas, circunferência de cintura, quadril e pescoço. Aplicamos os questionários de Berlim para determinar o risco de ter AOS, escala de sonolência de Epworth para verificar sonolência excessiva diurna e o questionário de Pittsburgh para verificar a qualidade do sono. Realizamos poligrafia noturna para determinar a presença e gravidade da AOS utilizando o índice de apneia-hipopneia (IAH, definido positivo quando >= 15 eventos/hora). Foi realizada medida de pressão arterial (PA) por meio da monitorização ambulatorial da pressão arterial (MAPA) e velocidade de onda de pulso (VOP) para avaliar rigidez arterial. Resultados: A amostra foi composta de 587 participantes (188 homens e 399 mulheres), com mediana de idade e intervalo interquartil = 44 (29 - 55) anos e IMC = 25,0 (22,1-28,6) kg/m2. Os sintomas sugestivos de AOS derivados dos questionários de Epworth, Berlim e Pittsburgh não se associaram com a presença de AOS; A AOS foi diagnosticada em 18,6% eventos/hora da população, A herdabilidade foi estimada em 26%, independente da obesidade e outros fatores de confusão. A mediana da PA foi mais alta, a ausência de descenso noturno da PA foi mais comum e o VOP mais alto em participantes com AOS do que sem AOS. Na regressão logística multivariada apenas a idade e a PA se associaram de forma significante com o VOP. Conclusões: A herdabilidade da AOS foi moderada (26%) em uma população rural. As alterações cardiovasculares presentes na AOS estão associadas a fatores de confusão em estudos familiares / Introduction: Obstructive sleep apnea (OSA) is a common disease in the general population and the presence can be partially explained by a genetic component. However, there is a strong interaction between OSA with confounding factors, including obesity. The main objective of this study is to determine the heritability of OSA in a Brazilian rural population. Methods: We studied families from the Baependi Heart Study. Participants were assessed for anthropometric measurements, waist, hip and neck circumferences. We used the Berlin questionnaire to determine the risk of having OSA, Epworth sleepiness scale to evaluated the presence of excessive daytime sleepiness and the questionnaire of Pittsburgh to verify the quality of sleep. Overnight Polygraph night was conducted to determine the presence and severity of OSA through the apnea-hypopnea index. Blood pressure was measured (BP) by ambulatory blood pressure (ABP) and pulse wave velocity (PWV) to assess arterial stiffness. Results: The sample consisted of 587 participants (188 men and 399 women), median and interquartile range of age = 44 (29-55) years and BMI = 25.0 (22.1 to 28.6) kg / m2. Symptoms suggestive of OSA derived from Epworth, Berlin and Pittsburgh questionnaires were not associated with the presence of OSA; OSA was diagnosed in 18.6% events/hour of the population, the heritability was estimated at 26%, independent of obesity and other confounding factors. BP was higher, the absence of nocturnal BP was more common and the highest VOP in participants with OSA than without OSA. Using multivariate logistic regression only age and BP were associated significantly with PWV. Conclusions: OSA heritability is moderate (26%) in a rural population. The cardiovascular alterations associated with OSA were explained by confounding factors

L’hypertension systolique isolée (HSI) est le résultat de changements au niveau de la paroi vasculaire qui ont pour conséquence d’augmenter la rigidité artérielle. Ces modifications surviennent surtout au niveau des grosses artères comme l’aorte et sont associées au vieillissement. La fragmentation des fibres élastiques, leur calcification (élastocalcinose) et la fibrose font partie des changements majeurs observés avec l’âge. En plus de ces changements, le vieillissement vasculaire provoque des modifications au niveau des cellules qui composent la paroi. Les cellules endothéliales sécrètent moins de monoxyde d’azote (NO) provoquant une dysfonction endothéliale et les cellules musculaires lisses vasculaires (CMLVs) synthétisent maintenant des protéines matricielles et osseuses. Situé entre le sang et les CMLVs, l’endothélium contrôle le tonus vasculaire par la sécrétion de plusieurs substances vasoactives qui interagissent entre elles afin de maintenir l’homéostasie du système vasculaire. Parmi celles-ci, on note l’endothéline (ET), un puissant vasoconstricteur et le NO, un gaz vasorelaxants. Ce dernier est aussi reconnu pour bloquer la production d’ET par un mécanisme dépendant du guanosine monophosphate cyclique (GMPc). Comme il y a une interaction entre le NO et l’ET, et que cette dernière est impliquée dans la calcification artérielle, le NO pourrait être impliqué dans la modulation de l’élastocalcinose et de la rigidité artérielle par l’inhibition de l’ET et la modification de la composition de la paroi. Cet effet, qui se produirait au delà des effets vasorelaxants du NO, offre un potentiel thérapeutique intéressant pour l’HSI. Afin d’évaluer l’implication du NO dans la calcification vasculaire et la rigidité artérielle, un modèle animal d’HSI a été utilisé (modèle warfarine vitamine K, WVK). Ce modèle d’élastocalcinose est basé sur l’inhibition de la maturation d’une protéine anti-calcifiante, la matrix Gla protein (MGP), par la warfarine. Afin de déterminer l’implication physiologique du NO dans l’initiation et la progression de l’élastocalcinose, sa production a été inhibée par un analogue de la L-arginine, le L-NG-nitroarginine methyl ester (L-NAME). Lors des processus d’initiation de la calcification, le L-NAME a prévenu l’élastocalcinose sans toutefois modifier la vitesse de l’onde de pouls (PWV). Suite au traitement L-NAME, l’expression de la NO synthase inductible (iNOS) a été diminuée alors qu’elle a été augmentée lors du traitement WVK. Elle pourrait donc être impliquée dans les processus de calcification vasculaire. De plus, la NO synthase endothéliale (eNOS) semble également impliquée puisqu’elle a été augmentée dans le modèle WVK. Cette hausse pourrait être bénéfique pour limiter l’élastocalcinose alors que l’expression de la iNOS serait délétère. Lors de la progression de la calcification, le L-NAME a augmenté l’élastocalcinose et le PWV. Dans ce contexte, l’ET serait impliquée dans l’amplification de la calcification vasculaire entrainant une hausse de la rigidité artérielle. Comme le NO endogène limite la progression de la calcification et conséquemment la rigidité artérielle, il semble être protecteur. L’efficacité d’une modulation de la voie du NO dans le modèle WVK a été étudiée par l’administration d’un donneur de NO, le sinitrodil, ou d’un inhibiteur de la phosphosdiestérase 5 (PDE5), le tadalafil. La modulation de la voie du NO semble être bénéfique sur la rigidité artérielle, mais seulement de façon aiguë. En effet, le sinitrodil a modifié de transitoirement la rigidité au niveau de l’aorte possiblement par la modulation du tonus vasculaire sans toutefois avoir des effets sur la composition de la paroi. Comme le modèle WVK n’affecte pas la fonction endothéliale, les concentrations endogènes de NO semblent être optimales puisque le sinitrodil provoque une augmentation de l’élastocalcinose possiblement par le développement d’une tolérance. Tout comme le sinitrodil, le tadalafil a modulé de manière aiguë la rigidité artérielle sans modifier la composition de la paroi. Globalement, ces travaux ont permis de mettre en évidence les effets bénéfiques du NO endogène pour limiter le développement de l’HSI, suggérant qu’une dysfonction endothéliale, tel qu’observé lors du vieillissement, a un impact négatif sur la maladie. / Isolated systolic hypertension (ISH) is the result of complex changes in the vascular wall and consequently the increase of arterial stiffness. These modifications occur mainly in conductance arteries, like the aorta, and are associated with aging. The fragmentation of elastic fibers, calcification (elastocalcinosis), and fibrosis are major changes with age. In addition to these changes in the extracellular matrix, vascular aging also induces vascular cell wall modifications. These include decreased production of nitric oxide (NO) by endothelial cells, which induces endothelial dysfunction, and the production of matrix and bone proteins by vascular smooth muscle cells (VSMCs). Located between the blood and VSMCs, the endothelium controls vascular tone by secreting various vasoactive factors. These factors interact with each other to maintain the hemodynamic of the vascular system. Among these factors, the vasoconstrictor endothelin (ET) and the vasodilator NO. The latter has been shown to block ET production via a cyclic guanosine monophosphates-(cGMP) dependent mechanism, whereas ET has been implicated in arterial calcification. Therefore, NO might be involved in the modulation of elastocalcinosis and arterial stiffness by inhibiting ET and modifying the vascular wall composition. This effect of NO could offer interesting therapeutic potential for ISH. To evaluate the implication of NO in the vascular calcification and arterial stiffness, an animal model of ISH was used. This model of elastocalcinosis is based on the inhibition of the maturation of the anti-calcific protein, matrix Gla protein (MGP), by warfarin (WVK model). To gain insight into the physiological role of endogenous NO in the initiation and progression of elastocalcinosis, its production was inhibited by the administration of L-NAME. Interestingly, elastocalcinosis was prevented by L-NG-nitroarginine methyl ester (L-NAME) administration without any modifications of the pulse wave velocity (PWV) during the initiation of the calcification processes. After the L-NAME treatment, the expression of inducible NO synthase (iNOS) was decreased, whereas upon treatment with warfarin alone the expression of iNOS was increased, which could be implicated in vascular calcification and arterial stiffness. In addition, endothelial NO synthase (eNOS) seems to be implicated in this process as its expression was also increased upon WVK treatment. This increase could be beneficial to limit elastocalcinosis, whereas the increase in iNOS expression could be harmful. L-NAME administration during the progression of calcification increased elastocalcinosis and PWV. In an endothelial dysfunction context, ET has been shown to be involved in the amplification process of vascular calcification causing an increase in arterial stiffness. As NO limits the progression of calcification and consequently arterial stiffness, endogenous NO seems to be protective in the aorta. The efficacy of exogenous modulation of the NO pathway in the WVK model was studied upon administration of the NO donor, sinitrodil, or the phosphodiesterase type 5 inhibitor (PDE5), tadalafil. The exogenous modulation of the NO pathway seemed to be beneficial for arterial stiffness, but only in an acute manner. Indeed, sinitrodil modified the acute stiffness in the aorta potentially by vascular tone modulation, without having any effect on vascular wall composition. Since endothelial function was not affected upon WVK model, endogenous NO concentrations seem to be optimal. Thus, exogenous NO potentially caused an increase of elastocalcinosis by inducing tolerance to NO. As well as sinitrodil, tadalafil modulated the arterial stiffness in an acute manner without modifying the composition of the vascular wall. Broadly, these studies provide evidence that endogenous NO can limit ISH development, suggesting that endothelial dysfunction, as observed in aging, has a negative impact on this pathology.

Beneš J.: HEMODYNAMIKA V ČASNÉ FÁZI KRITICKÝCH STAVŮ A PERIOPERAČNÍ MEDICÍNĚ - Využití méně invazivních monitorovacích prostředků k cílené hemodynamické péči ABSTRACT Hemodynamic instability occurs very often in critically ill patients and during the perioperative period. Insufficiency in the preload, contractility and afterload contribute in major part to this phenomenon. Hemodynamic monitoring allows clinicians to recognize and to intervene early the underlying cause. Due to new technologies development in recent years it is possible to provide continuous monitoring of hemodynamic parameters with diminished invasivity. Hemodynamic optimization and goal directed therapy show treatment benefit in some groups of critically ill patients and mainly during the perioperative period. Aim of hemodynamic optimizations is to attain the best obtainable hemodynamic conditions with use of fluid loading and inotropic support. In many studies in recent years goal-directed therapy was associated with morbidity and mortality reduction. According to the results of our clinical research hemodynamic optimization using stroke volume variation and minimally invasive device based on the pressure wave analysis is feasible and show the same results as other works with more invasive devices. Key words Hemodynamic monitoring,...

Arterial stiffness represented by carotid-femoral pulse wave velocity (PWV) is considered to be an independent cardiovascular risk factor. This study was focused on large artery properties investigation in specific forms of hypertension using applanation tonometer Sphygmocor (Atcor Medical). PWV was significantly higher in resistant hypertension patients when compared to moderate essential hypertension (EH) patients. This difference appears to be independent of clinical blood pressure (BP). Night-time BP appears to be a more accurate predictor of PWV in EH. In another study we demonstrated that primary hyperparathyroidism (PH) (both hypertensive or non-hypertensive forms) might be associated with higher PWV when compared to EH patients or to normotensive controls and that this difference is independent of age and clinical BP. Neither calcium serum level, nor parathyroid hormone has been associated with PWV. Specific treatment by parathyroidectomy (PTX) seems to be beneficial for PWV decrease, which might be mainly determined by improved BP control after surgery. Since PTX indications for asymptomatic forms of PH have been discussed, our data suggest the potential benefit to the extent of subclinical organ damage after surgical treatment in these patients. Similarly, we prooved higher PWV in...

Introdução: A apneia obstrutiva do sono (AOS) é uma condição clínica comum associada com o aumento do risco cardiovascular. No entanto, a maioria dos estudos envolvendo AOS e desfechos cardiovasculares recrutaram de forma preponderante os homens. Em pacientes hipertensos, a AOS pode contribuir para a lesão de órgãos-alvo e alterações no descenso noturno em homens. O impacto da AOS nas mulheres hipertensas é pouco estudado. O objetivo deste estudo é estudar o impacto da AOS na rigidez arterial da aorta (avaliada pela velocidade da onda de pulso, VOP, carótida-femoral), disfunção diastólica e alterações do descenso noturno da pressão arterial em ambos os gêneros. Fazemos a hipótese de que a AOS está associada com alterações na rigidez arterial, disfunção diastólica e comportamento da pressão arterial independente do gênero. Métodos: Recrutamos de forma consecutiva pacientes hipertensos estágio 2 do ambulatório de Hipertensão do Instituto do Coração. Padronizamos a medicação anti-hipertensiva (hidroclorotiazida 25mg ao dia e enalapril 20mg 2x ao dia ou losartan 50mg 2x ao dia em caso de intolerância ao enalapril) por 1 mês. A adesão do tratamento aconteceu por meio da contagem de pílulas. Foram realizadas avaliações da monitorização ambulatorial da pressão arterial (MAPA), VOP, ecocardiograma transtorácico, exames laboratoriais e a Polissonografia Noturna. A AOS foi diagnosticada por um índice de apneia e hipopneia >= 15 eventos por hora de sono. Resultados: Foram inicialmente recrutados 125 participantes e após as exclusões, avaliamos 95 pacientes hipertensos (56% mulheres). A frequência da AOS foi de 66,7% em homens e 45,3% em mulheres (p=0,02). Em relação às mulheres sem AOS, mulheres com AOS eram mais velhas, tinham maior índice de massa corpórea e apresentaram maiores circunferências cervical e abdominal. Os homens com e sem a AOS foram semelhantes em várias características, exceto por uma circunferência abdominal maior no grupo com AOS. Comparado aos pacientes sem AOS, a VOP foi estatisticamente maior nos homens portadores de AOS (11,1±2,2 vs. 12,7±2,4m/s, respectivamente; p=0,04), assim como nas mulheres (11,8±2,4 vs. 13,2±2,2m/s, respectivamente; p=0,03). Em relação à disfunção diastólica, apenas as mulheres com AOS mostraram maior porcentagem dessa alteração ecocardiográfica (46,1 vs. 81,8%, respectivamente; p=0,007). Foi visto nos resultados da MAPA, que homens com AOS apresentaram menor frequência do descenso noturno sistólico (46,4 vs. 14,3%, respectivamente; p=0,04) e as mulheres, uma tendência (65,2 vs. 41,4%; p=0,07). O resultado da regressão linear mostrou que a presença de AOS promove aumento independente nos valores da VOP. O resultado da regressão logística evidenciou que a presença da AOS não foi associada com a disfunção diastólica, mas foi com a ausência do descenso noturno do componente sistólico da pressão arterial. Conclusões: Em pacientes hipertensos, a presença da AOS foi associada com um aumento na rigidez arterial independente do sexo, assim como a ausência do descenso noturno do componente sistólico da pressão arterial. Estes dados sugerem que mulheres hipertensas também estão expostas às consequências vasculares da AOS / Introduction: Obstructive sleep apnea (OSA) is a common condition associated with increased cardiovascular risk. However, most of studies that addressed OSA and its cardiovascular consequences enrolled mainly men. In hypertensive patients, OSA may contribute to increased target organ damage and alterations in the blood pressure dipping in males. However, the impact of OSA in hypertensive females is not well established. In this study, we compared the impact of OSA on arterial stiffness of the aorta (evaluated by carotid-femoral pulse wave velocity, PWV), as well as diastolic dysfunction and blood pressure dipping in men and women with hypertension. We made the hypothesis that OSA is associated with higher arterial stiffness, higher frequency of diastolic dysfunction and impaired blood pressure behavior regardless of gender. Methods: We recruited consecutives stage 2 hypertensive patients from the outpatient clinic at the Heart Institute. We performed a 30-day standardized anti-hypertensive treatment with hydrochlorothiazide 25mg per day plus enalapril 20mg BID or losartan 50mg BID (if enalapril intolerance). Adherence to treatment was confirmed through pill counting. After that, all volunteers were submitted to clinical evaluation, carotid-femoral PWV, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiogram, and polysomnography. OSA was defined by an apnea-hypopnea index >= 15 events per hour. Results: We initially recruited 125 participants and after exclusions ninety-five patients were studied (56% women). OSA was present in 52 patients (men: 66.7%; women: 45.3%; p=0.02). In comparison to women without OSA, women with OSA were older, had higher body mass index and higher neck and abdominal circumferences. In men, there were no differences between OSA and no-OSA groups, except for higher values of abdominal circumference in OSA patients. Compared to no-OSA patients, PWV values were higher in the OSA group among both males (11.1±2.2 vs. 12.7±2.4m/s, respectively; p=0.04) and females (11.8±2.4 vs. 13.2±2.2m/s, respectively; p=0.03). The impact of OSA on diastolic dysfunction was significant only in females (46.1 vs. 81.8%, respectively; p=0.007). Regarding ambulatory blood pressure monitoring data, the frequency of systolic blood pressure dipping was significantly lower in men with OSA (46.4 vs. 14.3%, respectively; p=0.04) and marginal but non-significant in women (65.2 vs. 41.4%; p=0.07). Linear regression analysis showed that the presence of OSA was independently associated with higher PWV. In the logistic regression analysis, OSA was not associated with diastolic dysfunction but independently associated with nondipping systolic blood pressure. Conclusion: In patients with hypertension, OSA has significant associated with higher arterial stiffness and nondipping systolic blood pressure regardless of gender. These data suggest that hypertensive women are also exposed to the vascular and hemodynamic consequences of OSA

Objective: Despite the advanced therapy with statins, antithrombotics, and antihypertensive agents, the medical treatment of atherosclerotic disease is less than optimal. Therefore, additional therapeutic antiatherosclerotic options are desirable. This pilot study was performed to assess the potential antiatherogenic effect of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in nondiabetic patients. Methods: A total of 54 nondiabetic patients were observed in a prospective, double-blind, placebo-controlled study. Patients were randomized to pioglitazone or placebo. The following efficacy parameters were determined by serial analyses: artery pulse wave analysis and carotid-femoral pulse wave velocity (PWV), static and dynamic retinal vessel function, and the common carotid intima-media thickness (IMT). The main secondary endpoint was the change in different biochemical markers. Results: After 9 months, no relevant differences could be determined in the two treatment groups in PWV (pioglitazone 14.3 ± 4.4 m/s vs. placebo 14.2 ± 4.2 m/s), retinal arterial diameter (pioglitazone 112.1 ± 23.3 μm vs. placebo 117.9 ± 21.5 μm) or IMT (pioglitazone 0.85 ± 0.30 mm vs. placebo 0.79 ± 0.15 mm). Additionally, there were no differences in the change in biochemical markers like cholesteryl ester transfer protein, lowdensity lipoprotein cholesterol, high-sensitivity C-reactive protein or white blood cell count. Conclusions : Treatment with a peroxisome proliferator-activated receptor-γ agonist in nondiabetic patients did not improve the function of large and small peripheral vessels (PPP Trial, clinicaltrialsregister. eu: 2006-000186-11).

Arterial system is a system of vessels distributing blood. Ageing of arterial system leads to two distinct pathologies: atherosclerosis and arteriosclerosis - stiffening of arterial wall. These pathologies can coexist and interfere; however, they differ in their pathogenesis, location, scope and consequences. Progressive loss of elastic properties of large arteries is natural part of vascular ageing. It is directly responsible for several age dependent consequences, such as increase of central systolic pressure or prevalence of isolated systolic hypertension in the elderly. Clinically, central arteries stiffness manifests as aortic pulse wave velocity, which can be quantified, among other methods, using applanation tonometry. There is abundant evidence that aortic pulse wave velocity represents an independent predictor of cardiovascular mortality and morbidity. The most important mechanism in arterial stiffening is repeated mechanical damage which leads to fractures, fragmentation and thinning of elastin. Stiffening of large arteries can be accelerated by several other mechanisms, e.g. deposition of several substances (calcium, advanced glycation end-products, etc.), metabolic turnover of key elements of vascular extracellular matrix (collagen and elastin) or individual genetic susceptibility. In...