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

The mechanical properties of the arterial wall are of great importance for blood pressure regulation and cardiac load. With increasing age, large arteries are affected by increased wall stiffness. Furthermore, atherosclerotic manifestations may increase the stiffness even further, both processes acting as independent cardiovascular risk factors affecting the arterial system in a heterogeneous way. The aims of this thesis was to characterize the local mechanical properties of brachial artery (BA) with the aid of ultrasound technique and to evaluate the influence of 1) age, gender, sympathetic stimulation and examination site; 2) type 1 diabetes (DM) and its association to circulatory biomarkers; and 3) to evaluate the general properties of the arterial system with the aid of pulse wave velocity (PWV) as well as pulse wave analysis (PWA) in systemic lupus erythematosus (SLE) and correlate the findings to disease activity and circulatory biomarkers. In the most proximal arterial segment of the upper arm a pronounced age-related decrease in wall distensibility, increase in intima-media thickness (IMT), and a slight increase in diameter were seen. Sympathetic stimulation had no influence on wall mechanics. More distally in BA, no change in diameter, and only minor increase in IMT and decrease in distensibility were seen. No gender differences were found. These findings suggest that the principle transit zone between elastic and muscular artery behaviour is located in the proximal part of the upper arm. Women with uncomplicated insulin-dependent DM had similar diameter, IMT and distensibility in their distal BA as controls, whereas flow-mediated dilatation (FMD) was slightly, and nitrate mediated dilatation (NMD) markedly reduced. NMD was negatively correlated with higher HbA1c levels. Vascular smooth muscle cell function seems to be an early manifestation of vascular disease in women with DM, influenced by long-term hyperglycaemia. Women with SLE had increased aortic PWV compared to controls, a finding positively associated with increased levels of complement factor 3 (C3), but not with disease activity. The increased stiffness of central arteries may be one factor contributing to the increased cardiovascular risk seen in SLE.

<p>S obzirom na visoku prevalencu metaboličkog sindroma (10-40% u svetskoj populaciji) i na činjenicu da prisustvo metaboličkog sindroma duplira rizik od nastanka aterosklerotske bolesti kardiovaskularnog sistema jasna je potreba za identifikacijom indivudualnih parametara koji doprinose njenom razvoju. Metabolički sindrom je klaster faktora rizika metaboličkog porekla koji je udružen sa povećanim rizikom za nastanak aterosklerotske bolesti kardiovaskularnog sistema i dijabetes melitusa tipa 2. Insulinska rezistencija, abdominalna gojaznost, aterogena dislipidemija, hipertenzija, proinflamatorno i protrombotično stanje su faktori koji su u osnovi metaboličkog sindroma a često su i praćeni nagomilavanjem masti u jetri. Cilj rada je bio da se utvrdi odnos između markera disfunkcije hepatocita (AST, ALT, GGT), serumskog nivoa inflamatornih biomarkera (broj leukocita, elektroforeza serumskih proteina, CRP, fibrinogen, TNF-&alpha;), biomarkera endotelne disfunkcije (ADMA i homocistein), kao i nivoa serumskih adipokina (leptin i adiponektin) i debljine intima-medija kompleksa (IMT) karotidne arterije kao pokazatelja prisustva aterosklerotskog procesa. Ispitivanje je dizajnirano kao studija preseka. U ispitivanje je uključeno 58 ispitanika oba pola sa karakteristikama metaboličkom sindroma (NCEP:ATP III kriterijumi). Odabir ispitanika je vr&scaron;en u Odeljenju za pravilnu ishranu i zdravstvenu bezbednost hrane, Instituta za javno zdravlje Vojvodine. Kontrolnu grupu su sačinjavale 30 klinički i biohemijski zdravih ispitanika nepu&scaron;ača koji su prema polnoj i dobnoj strukturi odgovarali ispitivanim grupama bolesnika. Iz ispitivanja su isključene osobe koje konzumiraju vi&scaron;e od 20g/dan alkohola, pu&scaron;ači, koji imaju dijagnostikovan virusni hepatitis B ili C ili pozitivan Hbs antigen, anti-Hbs antitela i anti-HCV antitela, osobe koje imaju verifikovana oboljenja kardiovaskularnog sistema, bubrega, CNS-a, infektivna, maligna i autoimuna oboljenja kao i druga oboljenja jetre i žučnih puteva, osobe koje su pod medikamentoznom terapijom koja može uticati na nivo serumskih biomarkera endotelne disfunckije, lipidni i lipoproteinski status, glikoregulaciju kao i menstruacioni ciklus. Sve laboratorijske analize su urađene u Centru za laboratorijsku medicinu, Kliničkog centra Vojvodine. Doppler ultrasonografski pregled karotidnih arterija i ultrazvuk abdomena i jetre je urađen u Centru za radiologiju Kliničkog centra Vojvodine. Signifikantna pozitivna korelacija niskog stepena je utvrđena između IMT zajedničke karotidne arterije i serumskih koncentracija GGT, hsCRP i leptina kao i odnosa neutrofili/limfociti. Prema prvom konstruisanom regresionom modelu u kojem je zavisna varijabla bila IMT preko 0,09 cm statistički značajan uticaj na predviđanje debljine IMT zajedničke karotidne arterije imaju hsCRP (Exp (B) 1,112 i glikemija (Exp (B) 1,973). Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju glikemija, AST i fibrinogen. Prema drugom konstruisanom regresionom modelu gde su zavisne varijable bile IMT zajedničke karotidne arterije preko 0,09 cm i prisutnost hepatične steatoze najveću mogućnost predviđanja imaju leptin Exp (B) 1,1022 i ALT Exp (B) 1,053. Prema modelu neuronske mreže sa istom zavisnom varijablom najveću mogućnost predviđanja IMT imaju ALT, ADMA i leptin.</p> / <p>Given the high prevalence of metabolic syndrome (10-40% in the world population) and the fact that the presence of metabolic syndrome doubles the risk of atherosclerotic disease of the cardiovascular system, there is a clear need to identify individual parameters that contribute to its development. Metabolic syndrome is a cluster of the risk factors of metabolic origin that is associated with an increased risk for the onset of atherosclerotic disease of the cardiovascular system and type 2 diabetes mellitus. Insulin resistance, abdominal obesity, atherogenic dyslipidemia, hypertension, proinflammatory and prothrombotic conditions are the factors at the base of the metabolic syndrome and are often accompanied by fat accumulation in the liver. The aim of this work was to determine the relation between markers of hepatic dysfunction (AST, ALT and GGT), serum levels of inflammatory biomarkers (white blood cell count, electrophoresis of serum proteins, CRP, fibrinogen, TNF-&alpha;), biomarkers of endothelial dysfunction (ADMA and homocysteine) as well as levels of serum adipokines (leptin and adiponectin) and intima-media thickness of carotid artery as indicators of atherosclerotic process in the patients with metabolic syndrome. Study was cross-sectional. It included 58 participants with metabolic syndrome (NCEP:ATP III criteria) as well as 30 clinically and biochemically healthy nonsmokers, age and gender matched controls. Participants were selected in the Department for Nutrition and Food Safety, Center of Hygiene and Human Ecology Institute of Public Health of Vojvodina. Patients that consumed alcohol more than 20g/day were excluded. Participants with positive HBsAg, anti-HBs-antibodies or anti- HCV antibodies were excluded also. Smokers were also excluded. Patients with cardiovascular diseases, renal diseases, infective, hepatic, malignant and autoimmune diseases were excluded from this study. Subjects which used drugs that could affect biomarker levels of endothelial dysfunction, lipid metabolism, glucose metabolism and menstrual cycle were also excluded. All laboratory analyzes were done in Centre for Laboratory Medicine, Clinical Centre of Vojvodina. Doppler ultrasonography of carotid arteries and ultrasound of abdomen and liver were done in Centre for Radiology, Clinical Centre of Vojvodina. Significant positive correlation of low degree was determined between IMT of common carotid artery and serum concentrations between GGT, hsCRP and leptin and relationship neutrophils/lymphocytes. According to the first constructed regression model where dependent variable was IMT of common carotid artery above 0.09 cm statistically significant influence on foreseeing IMT of common carotid artery have hsCRP (Exp (B) 1.112 and glycaemia (Exp (B) 1.973). According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have glycaemia, AST and fibrinogen. According to the second constructed regression model where dependent variable was IMT above 0.09 cm and present hepatic steatosis greatest probability for foreseeing IMT have leptin Exp (B) 1.1022 and ALT Exp (B) 1.053. According to the neuronal network with the same dependent variable greatest probability for foreseeing IMT have ALT, ADMA and leptin.</p>

O HDL-c é um fator de risco cardiovascular negativo e sua concentração plasmática apresenta relação inversa com a incidência de eventos cardiovasculares. Entretanto, as evidências relativas ao grupo de indivíduos com níveis de HDL-c acima do percentil 95 da população geral ainda são escassas e o impacto da hiperalfalipoproteinemia (HALP) sobre o risco cardiovascular continua representando motivo de controvérsia na literatura médica. Alguns estudos em populações específicas associam a HALP a aumento do risco cardiovascular. Ao mesmo tempo, outros estudos identificaram populações de indivíduos hipoalfalipoproteinêmicos com marcada longevidade. Assim, demonstrou-se aparente dissociação entre níveis de HDL-c e risco cardiovascular em determinadas populações, reconduzível a aspectos disfuncionais da HDL. O objetivo do presente estudo foi verificar o papel da HALP na determinação do risco cardiovascular; comparar a prevalência de doença cardiovascular subclínica, avaliada por meio da quantificação ultrassonográfica da Espessura Íntimo-Medial Carotídea (EIMC), entre portadores de HDL-c >= 90mg/dL (grupo HALP) e portadores de concentrações de HDL-c atualmente consideradas normais (entre 40 e 50mg/dL para os homens e entre 50 e 60mg/dL para as mulheres); e avaliar características e função da HDL em portadores de HALP por meio do estudo de sua composição, de sua capacidade de efluxo de colesterol, e de sua atividade anti-inflamatória e antioxidante, correlacionando estas características com a presença de doença cardiovascular subclínica avaliada por meio da determinação da EIMC, da Velocidade de Onda de Pulso (VOP) e da presença de Calcificação Arterial Coronariana (CAC) avaliada pela TCMD. Para responder estas perguntas, o presente estudo foi articulado em dois braços: Braço 1: Análise da coorte do estudo ELSA com o objetivo de determinar a prevalência de HALP em uma população geral; definir o perfil demográfico, antropométrico e metabólico dos portadores de HALP; e comparar a prevalência de doença vascular subclínica deste grupo com controles da mesma coorte com níveis normais de HDL-colesterol. Braço 2: Recrutamento de 80 voluntários hígidos e portadores de HALP para avaliação da correlação entre presença de doença vascular subclínica, e aspectos estruturais e funcionais da HDL. Em seus dois braços, o estudo levou a quatro conclusões principais: 1) Níveis marcadamente elevados de HDL-c estão associados a menor espessura íntimo-medial carotídea quando comparados a níveis de HDL-c considerados normais pelas diretrizes vigentes. Embora portadores do fenótipo HALP apresentem, como grupo, um perfil metabólico mais favorável que o encontrado em indivíduos com HDL-c normal, a associação entre EIMC e HALP foi independente dos fatores de risco tradicionais, indicando que a menor prevalência destes últimos em portadores de HDL-c marcadamente elevado justifica apenas parcialmente a menor prevalência de doença vascular subclínica neste grupo; 2) Embora a HALP se apresente como um fenótipo ateroprotetor, há indivíduos com níveis marcadamente elevados de HDL-c que evoluem com doença cardiovascular, clínica ou subclínica. Neste contexto, nossos resultados indicam correlação entre os três métodos avaliados para estudar doença vascular subclínica em portadores de HALP: EIMC, VOP e CAC; 3) Os fatores de risco tradicionais continuam exercendo seu peso na determinação do risco cardiovascular em portadores de HALP. Idade, tabagismo, hipertensão arterial, hipertrigliceridemia e altos níveis de LDL-c apresentaram associação estatisticamente significativa com a presença de doença vascular subclínica no grupo estudado; 4) A avaliação da composição e da função da HDL em portadores de HALP pode permitir identificar indivíduos especificamente mais suscetíveis à aterosclerose. Nossos resultados indicam que, em particular, a atividade anti-inflamatória da HDL, avaliada pela capacidade de inibição da produção de IL-6; o efluxo de colesterol e a capacidade de transferência de triglicérides apresentaram associação independente com menor espessura íntimo-medial carotídea em portadores de HALP, enquanto níveis mais altos de Apo A-IV se associaram a maior grau de doença cardiovascular subclínica / HDL-c is a negative cardiovascular risk factor and its plasma concentration is inversely related to the incidence of cardiovascular events. However, evidence of benefit among subjects with HDL-c levels above the 95th percentile of the general population is still scarce and the impact of hyperalphalipoproteinemia (HALP) on cardiovascular risk continues to represent matter of debate in the medical literature. Some studies with specific populations indicated an increased cardiovascular risk associated with HALP. In addition, other reports identified groups of patients with marked hypoalphalipoproteinemia and longevity. Hence, there could be a dissociation between HDL-c levels and cardiovascular risk in certain populations, possibly due to dysfunctional HDL particles. The aim of this study was to investigate the role of HALP phenotype in determining cardiovascular risk; to compare the prevalence of subclinical cardiovascular disease, assessed by ultrasound measurement of Carotid Intima-Media Thickness (CIMT) among patients with HDL-c >= 90mg/dL (HALP group) and patients with HDL-c currently considered normal (40-50mg/dL for men and 50-60mg/dL for women); and to evaluate HDL functionality in patients with HALP through the study of its composition, its cholesterol efflux capacity, and its anti-inflammatory and antioxidant activity; correlating those characteristics with the presence of subclinical cardiovascular disease assessed by CIMT, Pulse Wave Velocity (PWV) and Coronary Artery Calcification (CAC). To answer these questions, the present study was articulated into two arms: Arm 1: ELSA-Brasil study cohort analysis in order to assess HALP prevalence in a general population, defining demographic, anthropometric and metabolic profile of HALP individuals; and comparing the prevalence of subclinical vascular disease among HALP subjects with controls with normal HDL-c. Arm 2: Recruitment of 80 healthy volunteers with HALP to study the correlation between subclinical vascular disease and HDL functionality in this group. Our study led to four main conclusions: 1) markedly elevated HDL-c is associated with lower CIMT compared to the control group with normal HDL-c levels. Although individuals with HALP display a more favorable metabolic profile than subjects with normal HDL-c, the association between CIMT and HALP was independent of traditional risk factors, indicating that the lower prevalence of subclinical vascular disease in this group is only partially justified by the lower prevalence of cardiovascular risk factors; 2) Although HALP can be regarded as an atheroprotective phenotype, there are individuals with markedly elevated levels of HDL-c who develop cardiovascular disease. Our results indicate good correlation of the three methods here adopted to study subclinical vascular disease among HALP patients: CIMT, VOP and CAC; 3) Traditional risk factors continue to exert their weight in determining cardiovascular risk in patients with HALP. Age, smoking, hypertension, hypertriglyceridemia and high levels of LDL-c were significantly associated with the presence of subclinical vascular disease among HALP individuals; 4) the assessment of the HDL composition and functionality in patients with HALP may allow to identify individuals specifically more susceptible to atherosclerosis. Our results indicate that, in particular, cholesterol efflux capacity, the anti-inflammatory activity of HDL, and triglyceride transfer capacity were independently associated with lower CIMT in HALP individuals, while higher levels of Apo A-IV were associated with a greater burden of subclinical cardiovascular disease

A obesidade é uma doença crônica com complicações para a qual se busca o tratamento e a prevenção. A gordura visceral é um órgão endócrino de armazenamento hormonal e produtor de adipocinas inflamatórias, tornando o obeso portador de inflamação crônica, que por sua vez é uma das características da aterogênese e do envelhecimento. Os níveis aumentados de interleucina-6 e fator de necrose tumoral-alfa, citocinas multifuncionais, estão associados à morbi-mortalidade em idosos e à patogênese da aterosclerose. Nos dias atuais, a alimentação mundial é caracterizada pelo aumento do consumo de gordura saturada e gorduras trans, bem como pela redução do consumo de ácidos graxos ômega-3. O desequilíbrio na relação ômega-6/ômega-3 propicia um ambiente de inflamação crônica, sendo o estímulo inicial para doenças degenerativas. A substituição de gorduras saturadas por ácidos graxos poliinsaturados, de ácido alfa- linolênico (ALA) - ômega-3, e de ácido graxo monoinsaturado (ácido oléico - ômega- 9), parece estar associada à redução do risco de doença cardiovascular. Entre duas fontes de ácido eicosapentaenóico e ácido docosahexaenóico, os ácidos graxos ômega-3 provenientes de peixes e o ALA das fontes vegetais, este último é mais acessível financeiramente e amplamente disponível no mundo todo. Este estudo foi desenhado para avaliar comparativamente o efeito do aumento do consumo de ALA proveniente de fontes vegetais sobre os indicadores inflamatórios e a reatividade endotelial em pacientes idosos e obesos ou com sobrepeso. Foram selecionados 79 pacientes para receber doses diárias de óleo de linhaça, óleo de oliva e óleo de girassol por 12 semanas consecutivas. Foram realizadas medidas antropométricas, bioquímicas e de reatividade endotelial antes e após a intervenção, sem nenhuma modificação na dieta dos participantes ou em suas medicações utilizadas, não havendo mudanças antropométricas após a conclusão do estudo. Houve melhora em alguns parâmetros bioquímicos com o óleo de linhaça, que reduziu os níveis de PCRus, C3, C4 e fibrinogênio; com o óleo de girassol, que reduziu os níveis de leptina, ApoB e também a relação Apo B/ApoA1; e com o óleo de oliva que beneficiou a relação Apo B/ApoA1 e os níveis de C4. A espessura da artéria carótida também teve melhora significativa com os três óleos suplementados, mais acentuada com o óleo de linhaça e o óleo de oliva. Além disto, o óleo de girassol melhorou significativamente a distensibilidade da parede arterial e da vasodilatação fluxo-mediada (VFM) e o óleo de oliva apresentou tendência de melhora na VFM. Concluímos que a suplementação de ácidos graxos insaturados provenientes dos três óleos vegetais atenuou o quadro pró-inflamatório e pró-trombótico. Ocorreu melhora do perfil de marcadores bioquímicos e resultados significativos estatisticamente nos marcadores de reatividade endotelial como redução da espessura da íntima-média da artéria carótida, melhora da distensibilidade da parede arterial e melhora da funcionalidade medida pela VFM. Foi benéfica sua introdução à dieta, a fim de reduzir o risco cardiovascular em idosos portadores de obesidade ou sobrepeso / Obesity is a chronic disease with complications for which treatment and prevention are sought. Visceral fat is an endocrine organ of hormonal storage and a producer of inflammatory adipokines, leading to chronic inflammation in the obese person, which in turn is one of the characteristics of atherogenesis and aging. Increased levels of multifunctional cytokines, interleukin-6 and tumor necrosis factor-alfa are associated with morbidity and mortality in the elderly, and in the pathogenesis of atherosclerosis. Currently, food worldwide is characterized by increased consumption of saturated and trans fats, as well as reduced consumption of omega-3 fatty acids. Imbalance in the omega-6/omega-3 ratio provides an environment of chronic inflammation, and the initial stimulus for degenerative diseases. The substitution of saturated fats by polyunsaturated fatty acids, alfa-linolenic acid (ALA)- omega-3, and mono-unsaturated fatty acid (omega-9 fatty acids), seems to be associated with reduced risk of cardiovascular disease. Obtaining alfa-linolenic acid from vegetable sources is more financially accessible and widely available worldwide than omega-3 fatty acids from fish; both are sources of eicosapentaenoic acid and docosahexaenoic acid. This study was designed to comparatively evaluate the effect of increased ALA consumption, derived from vegetables, on inflammatory indicators and the endothelial reactivity in obese or overweight elderly patients. Seventy nine patients were selected to receive daily doses of linseed oil, olive oil and sunflower oil for 12 consecutive weeks. Anthropometric, biochemical and endothelial reactivity measurements were performed before and after the intervention, without any changes in the participants\' diet or in their medications, and no anthropometric changes were identified after the conclusion of the study. Improvement in some biochemical parameters were identified with linseed oil, which reduced the levels of C-reactive protein, C3, C4 and fibrinogen; with sunflower oil, which reduced levels of leptin, ApoB and also ApoB/ApoA1 ratio; and with the olive oil that improved the ApoB/ApoA1 ratio and the C4 levels. Carotid artery thickness also showed a significant improvement with the three supplemented oils, and was more accentuated with linseed oil and olive oil. In addition, sunflower oil significantly improved the distensibility of the arterial wall and its flow-mediated dilatation (FMD), and olive oil showed a tendency for improvement in FMD. We concluded that the supplementation of unsaturated fatty acids from the three vegetable oils attenuated the pro-inflammatory and prothrombotic conditions. An improvement in the profile of biochemical markers and statistically significant results was identified in markers of endothelial reactivity, such as reduction of carotid artery intima-media thickness, improvement of the arterial wall distensibility and the endothelial function measured by FMD. The introduction of unsaturated fatty acids in the diet was beneficial, in order to reduce cardiovascular risk in obese or overweight elderly

Made available in DSpace on 2016-01-26T12:51:40Z (GMT). No. of bitstreams: 1 erosdamotadias_dissert.pdf: 1356790 bytes, checksum: 1ece28a3152d142febf47e53f4b83f1e (MD5) Previous issue date: 2012-07-25 / Introduction- The role of hypertension in the loss of cognitive function is controversial. Relationships of hypertension with increases in cerebral vascular resistance, diffused lesions and multiple lacunars infarct of the white matter are well known. Objectives- To evaluate the relationship between hypertension and cognitive deficiency (CD), identify risk factors associated with the development of CD and determine the association between markers of early vascular disease and CD in hypertensive individuals. Methods- One hundred and ninety eight individuals aged between 40 and 80 years old were evaluated. Forty eight participants were normotensive (NT). The remaining 150 hypertensive patients were subdivided into two groups, those with CD (HCD) and those without CD (HNCD). All participants underwent clinical evaluations and complete physical examinations and biochemical blood tests were performed. CD was investigated using the Mini Mental State Examination (MMSE) following the guidelines for its use in Brazil. The impact of hypertension on the arterial bed was assessed by identifying and measuring changes in the intima-media thickness (IMT) by vascular ultrasonography of the carotid arteries and analyses of the central blood pressure and Augmentation Index by applanation tonometry of the radial artery. Results- There were no significant differences in the plasma concentrations of total cholesterol, high density lipoprotein cholesterol and triglycerides of the three groups. The serum creatinine and estimated glomerular filtration rate where within normal ranges for all three groups. However, significantly higher values were found for the HCD and HNCD Groups compared to the NT Group (p-value < 0.05). A significantly lower MMSE score was recorded for the HCD Group compared to the HA and NT Groups (p-value < 0.05). The IMT was significantly different between the HNCD and HCD Groups (p-value = 0.0124). A significant difference in the IMT was also observed between hypertensive patients and the NT Group (p-value < 0.0001). The central systolic pressure was significantly higher in the HCD and HNCD Groups compared to NT Group (p-value < 0.0001). There were no significant differences in the Augmentation Index (corrected for heart rate) between the three groups (HNCD, HCD and NT). Conclusions- Hypertensive patients with CD have changes in the vascular morphology characterized by an increased carotid IMT and hemodynamic functional impairment manifested by elevated central systolic blood pressure. / Introdução- O papel da Hipertensão Arterial Sistêmica (HAS) no desenvolvimento de disfunção cognitiva é controverso. Reconhece-se sua relação com o aumento da resistência vascular cerebral e com lesões difusas e infartos lacunares múltiplos na substância branca. Objetivos- Avaliar a relação entre HAS e Déficit Cognitivo (DC), identificar fatores de risco associados a DC e identificar marcadores precoces de doença vascular e DC em hipertensos. Casuística e métodos- Foram avaliados 198 indivíduos com idades entre 40 e 80 anos, dos quais 150 eram hipertensos subdivididos em dois grupos, Hipertensos com DC (HA-DC) e Hipertensos sem DC (HA) e 48 indivíduos normotensos (NT). Todos foram submetidos à avaliação clínica, exame físico completo e exames bioquímicos de sangue. O DC foi investigado mediante o Mini Exame do Estado Metal (MEEM) segundo os critérios cujo uso é recomendado no Brasil. A repercussão da HAS no leito arterial foi rastreada por meio da identificação e quantificação de alteração na Espessura Íntima Média (EIMc) das carótidas com Ultrassonografia Vascular Digital e análise da Pressão Arterial Central (PSC) e do Augmentation Index (AI) mediante Tonometria por Aplanação (TA) da artéria radial. Resultados- As concentrações plasmáticas do colesterol total, colesterol de lipoproteína de alta densidade (HDL) e triglicérides (TG) nos três grupos estudados não mostraram diferenças significantes. Os valores de creatinina sérica e a Taxa de Filtração Glomerular estimada (TFGe) encontram-se dentro da faixa de normalidade nos três grupos. Entretanto valores maiores foram observados nos grupos HA-DC e HA, quando comparados ao grupo NT (p < 0,05). O grupo HA-DC confirmou redução significante do escore do MEEM quando comparado aos grupos HA e NT ( p <0,05). Avaliação da EIMc mostrou diferença significante entre os grupos HA e HA-DC (p=0,0124). Por outro lado, também observamos diferença significante para EIMc entre hipertensos e controles (p < 0,0001). Os grupos HA-DC e HA evidenciaram aumento significante da pressão sistólica central (PSC), quando comparados ao grupo NT (p < 0,0001). Os resultados do Augmentation Index 75 (corrigido para FC), avaliados nos três grupos (HA, HA-DC e NT) não apresentaram diferença significante. Os resultados do presente estudo mostraram: presença de alterações morfológicas caracterizadas por aumento da espessura íntima média das carótidas e alterações funcionais qualificadas como elevação da pressão sistólica central no grupo de hipertensos com DC. Entre os fatores de risco para o desenvolvimento de DC apenas a idade foi associada com déficit do escore do MEEM. Conclusões- Hipertensos com DC apresentam alterações morfológicas vasculares caracterizadas por aumento da espessura íntima média das carótidas e comprometimento hemodinâmico funcional manifesto por elevação de pressão sistólica central.

<p>Postmenopausal estrogen therapy, initiated early in the menopause, seems to protect against development of atherosclerosis and cardiovascular diseases. This thesis concerns studies of artery wall thickness and arterial stiffness estimated by noninvasive ultrasound techniques in long-term estrogen treated postmenopausal women who initiated therapy at the time of the menopause.</p><p>A noninvasive 25 MHz high-frequency ultrasound technique was validated in the imaging of superficial arteries by using an animal model. Ultrasound estimates of the artery wall layers obtained <i>in vivo</i> in the pig were compared to <i>ex-vivo</i> histomorphometry. Valid estimates of total artery wall and media thickness were found for the most superficial arteries. Adventitia thickness was underestimated and intima thickness overestimated in this animal model when non-atherosclerotic vessels were imaged.</p><p>To validate the clinical usefulness of separately estimating the artery wall layers in the human, the carotid artery wall was imaged in elderly subjects. Separate estimates of intima thickness, media thickness and intima/media ratio differed significantly between subjects with and without atherosclerosis and CVD, indicating that this noninvasive high-frequency ultrasound method might be a strong tool in monitoring changes in artery wall morphology associated with aging and development of atherosclerosis.</p><p>The investigation of intima thickness, media thickness and intima/media ratio of the carotid and femoral arteries in long-term estrogen treated postmenopausal women showed a maintenance of a thin intima and a preservation of media thickness and intima/media ratio at values similar to those obtained in women of fertile age. By comparing estrogen-users with age-matched postmenopausal nonusers, long-term estrogen therapy initiated at the time of the menopause seemed to counteract the increase in intima and decrease in media thickness associated with aging and development of atherosclerosis. The preservation of the artery wall morphology into older age might be a mechanism for the well-documented cardioprotective effects of estrogen when therapy is initiated early after menopause. However, long-term estrogen therapy showed no substantial effects on the age-related changes in arterial stiffness estimated at the aorta, carotid and femoral arteries, suggesting that any long-term cardioprotective effect that estrogen therapy may have is unlikely to be mediated by an impact on arterial stiffness. </p>

Postmenopausal estrogen therapy, initiated early in the menopause, seems to protect against development of atherosclerosis and cardiovascular diseases. This thesis concerns studies of artery wall thickness and arterial stiffness estimated by noninvasive ultrasound techniques in long-term estrogen treated postmenopausal women who initiated therapy at the time of the menopause. A noninvasive 25 MHz high-frequency ultrasound technique was validated in the imaging of superficial arteries by using an animal model. Ultrasound estimates of the artery wall layers obtained in vivo in the pig were compared to ex-vivo histomorphometry. Valid estimates of total artery wall and media thickness were found for the most superficial arteries. Adventitia thickness was underestimated and intima thickness overestimated in this animal model when non-atherosclerotic vessels were imaged. To validate the clinical usefulness of separately estimating the artery wall layers in the human, the carotid artery wall was imaged in elderly subjects. Separate estimates of intima thickness, media thickness and intima/media ratio differed significantly between subjects with and without atherosclerosis and CVD, indicating that this noninvasive high-frequency ultrasound method might be a strong tool in monitoring changes in artery wall morphology associated with aging and development of atherosclerosis. The investigation of intima thickness, media thickness and intima/media ratio of the carotid and femoral arteries in long-term estrogen treated postmenopausal women showed a maintenance of a thin intima and a preservation of media thickness and intima/media ratio at values similar to those obtained in women of fertile age. By comparing estrogen-users with age-matched postmenopausal nonusers, long-term estrogen therapy initiated at the time of the menopause seemed to counteract the increase in intima and decrease in media thickness associated with aging and development of atherosclerosis. The preservation of the artery wall morphology into older age might be a mechanism for the well-documented cardioprotective effects of estrogen when therapy is initiated early after menopause. However, long-term estrogen therapy showed no substantial effects on the age-related changes in arterial stiffness estimated at the aorta, carotid and femoral arteries, suggesting that any long-term cardioprotective effect that estrogen therapy may have is unlikely to be mediated by an impact on arterial stiffness.

[Truncated abstract] An elevated total plasma homocysteine concentration (tHcy) is associated with an increased risk of myocardial infarction and ischemic stroke. Folic acid, vitamin B6 and B12 supplements significantly reduce tHcy even in people who are not overtly vitamin deficient. If homocysteine is a causal risk factor for atherothrombotic events, treatment with B-vitamins might prove a simple and cost-effective means to reduce cardiovascular risk. However, it remains unclear whether elevated tHcy causes atherosclerosis or is simply a risk marker. To prove that homocysteine is a modifiable risk factor for cardiovascular disease it is necessary to show that lowering tHcy reduces vascular risk. The aim of this study was to determine whether long-term homocysteine-lowering with B-vitamins would improve vascular structure and function in people with a history of stroke. This study was a cross-sectional sub-study of the Vitamins TO Prevent Stroke trial (VITATOPS), a multi-centre, randomised, double-blind, placebo-controlled clinical trial designed to test the efficacy and safety of B-vitamins (folic acid 2mg, vitamin B6 25mg and vitamin B12 0.5mg) in the prevention of vascular events in patients with a recent history of stroke or transient ischemic attack. 173 VITATOPS participants were recruited for the current study. Age, sex, stroke type, medications, cardiovascular risk factors and smoking history were recorded and blood pressure, height, weight, waist and hip girth were measured in all subjects at least two years after randomisation. ... After a mean treatment period of 3.9 ± 0.9 years, the subjects randomised to vitamin treatment had significantly lower tHcy than the subjects randomised to placebo (7.9mol/L, 95%CI 7.5, 8.4 versus 11.8mol/L, 95%CI 10.9, 12.8; p<0.001). There were no significant differences between groups in CIMT (0.84 ± 0.17mm vitamins versus 0.83 ± 0.18mm placebo; p=0.74) or FMD (median of 4.0%, IQR 0.9, 7.2, vitamins versus 3.0%, IQR 0.6, 6.6 placebo; p=0.48). Pooled estimates from the meta-analyses showed that B-vitamin treatment reduces CIMT by 0.10mm (95%CI –0.20, -0.01mm) and increases FMD by 1.4%, (95%CI 0.7, 2.2), although these estimates may have been influenced by positive publication bias. The improvement in FMD was significant in studies of less than eight weeks duration but not in studies with longer treatment periods. The association between tHcy and CIMT and FMD was eliminated by adjustment for renal function and long-term B-vitamin treatment did not alter the strong linear relationship between tHcy and cystatin C. Lowering tHcy did not alter arterial wall inflammation assessed by 18FDG-PET, although small subject numbers meant we were unable to exclude a minor treatment effect. Long-term homocysteine-lowering with B-vitamin treatment did not improve CIMT or FMD or reduce arterial wall inflammation in people with a history of stroke. The relationship between tHcy and these markers of vascular risk was eliminated by adjustment for renal function. Our data are consistent with the hypothesis that elevated tHcy is a risk marker for cardiovascular disease rather than a modifiable causal risk factor.

A disfunção erétil (DE) tem alta prevalência entre hipertensos e tem sido considerada marcador precoce de risco cardiovascular. A presença e gravidade da DE bem como a resposta clínica aos inibidores da fosfodiesterase tipo 5 (PDE5) parecem depender da biodisponibilidade do óxido nítrico (NO) endotelial e da extensão da doença aterosclerótica. O objetivo deste estudo foi avaliar a resposta clínica da vardenafila usada em dois regimes terapêuticos em hipertensos com DE vasculogênica e sem doença cardiovascular maior, correlacionando a gravidade da DE e a eficácia da vardenafila com dados antropométricos, laboratoriais, escore de risco cardiovascular e parâmetros vasculares funcionais e estruturais. A resposta clínica à vardenafila nos dois regimes foi avaliada conforme o percentual de respostas positivas à questão 3 do Perfil do Encontro Sexual (PES3). Os parâmetros vasculares considerados foram a espessura médio-intimal (EMI) da carótida comum, a dilatação mediada pelo fluxo (DMF) da artéria braquial e a dilatação nitrato-mediada (DNM). Foram incluídos 100 homens hipertensos com idade entre 50 e 70 anos, sendo 74 portadores de DE vasculogênica e 26 com função erétil normal que serviram de grupo controle. Nos pacientes com DE, o índice de massa corporal, relação cintura-quadril, EMI da carótida, níveis séricos de triglicerídeos, colesterol total e LDL foram significativamente maiores que no grupo controle. Após o uso de vardenafila on demand (fase 1), os pacientes com mais de 50% de respostas positivas ao PES3 ou 50% de respostas afirmativas e um incremento de 6 pontos ou mais em relação ao Índice Internacional de Função Erétil (IIEF-FE) basal e/ou resposta positiva a Questão de Avaliação Global (QAG), foram considerados respondedores. O escore do IIEF-FE basal se correlacionou negativamente com a EMI da carótida (r=-0,48, P<0,001) e com o escore de Framingham (r= -0,41, P<0,001) no grupo com DE. Houve forte correlação positiva entre a resposta clínica à vardenafila com a DMF (r= 0,70, P<0,001), que não se observou entre o sub-grupo de diabéticos. Os 35 pacientes considerados não-respondedores na fase 1 foram randomizados e, em desenho duplo-cego, receberam vardenafila ou placebo diariamente durante cinco semanas, podendo usar 10 mg de vardenafila uma hora antes da atividade sexual (fase2). Houve resposta clínica positiva em 38,8% dos que receberam a vardenafila na fase 2 e esta resposta se correlacionou com a frequência sexual (r= 0,68, P<0,01) e com o escore de Framingham (r= -0,65, P<0,01), com a EMI da carótida (r= -0,61, P=0,01) e com o LDL-colesterol (r= -0,64, P<0,01). A vardenafila foi bem tolerada em ambos os regimes terapêuticos. Concluímos que nessa amostra de hipertensos, a gravidade da DE foi relacionada a parâmetros vasculares estruturais (EMI), enquanto a resposta clínica à vardenafila on demand foi mais diretamente dependente da função vascular momentânea (DMF). Houve benefício na utilização de vardenafila diariamente com o objetivo de resgatar a eficácia do inibidor quanto à melhora do desempenho sexual. A falta de eficácia clínica ao inibidor da PDE5 em ambos os regimes terapêuticos pode servir como marcador clínico que identifica homens hipertensos com um risco cardiovascular aumentado. / Erectile dysfunction (ED) is a high prevalent disease in hypertensive subjects and has been considered an early cardiovascular risk marker. EDs presence and severity, as well as clinical response to phosfodiesterase type 5 (PDE5) inhibitors, vary according to nitric oxide (NO) availability and atherosclerosis extension. We investigated whether vasculogenic ED severity and clinical response to vardenafil used on demand or continuously were associated with structural and functional vascular changes in patients with uncomplicated hypertension. Our main efficacy criterion was per patient percentage of positive answers on Sexual Encounter Profile question 3(SEP3). Vascular parameters considered were intima-media thickness (IMT), flow-mediated dilation (FMD) on brachial artery and nitrate-mediated dilation. A total of 100 hypertensive men aging between 50 and 70 years were included. Among these patients, 74 had vasculogenic ED and 26 presented normal erectile function according to erectile domain of International Index of Erectile Function (IIEF-EF). Among those with ED, body mass index, waist-rip ratio, carotid IMT, triglycerides, total cholesterol and LDL-cholesterol were significantly higher than controls. After vardenafil on demand usage during phase 1, patients with more than 50% of positive answers on SEP3 or 50% and more than 6 points on IIEF basal score or positive answer to global evaliation question were considered responders. IIEF basal score correlated inversely with carotid IMT (r=-0.48, P<0.001) and with Framingham risk score (r= -0.41, P<0.001) in ED group. Clinical response to vardenafil strongly correlated with FMD (r= 0.70, P<0.001), except among diabetics. Non responders (n=35) on phase 1 were included on phase 2 when, after randomization, they received vardenafil 10 mg nightly or placebo during five weeks. Open vardenafil on demand were allowed one hour before sexual intercourse, and 38.8% of active group improved and became responders to vardenafil. Clinical response on phase 2 correlated with sexual frequency (r= 0.68, P<0.01), Framingham score (r= -0.65, P<0.01), carotid IMT (r= -0.61, P=0.01) and LDL-cholesterol (r= -0.64, P<0.01). We concluded that in hypertensive males with vasculogenic ED and no other clinical evidence of atherosclerosis, ED severity correlated with structural parameters (carotid IMT), while phosphodiesterase-5 effectiveness correlated with functional vascular aspects (brachial FMD). There were positive impact with continuous vardenafil on non responders to on demand regime and that could be an option to salvage strategy. Lack of PDE5 inhibitor efficacy in both therapeutic strategies could point out to higher cardiovascular risk and could be considered a useful clinical marker.