Evaluation of Collagen Fibers, MMP2, MMP9, 8-OHdG and Apoptosis in the Aorta of Ovariectomized LDL Knockout Mice Submitted to Aerobic Exercise / Avaliação de Fibras de Colágeno, MMP2, MMP9, 8-OH-Dg e Apoptose na Aorta de Ratas LDL Nocaute Ovariectomizadas Submetidas a Exercício Aeróbico

Abstract Background: In menopause, there is greater cellular exposure to oxidative stress, related to the decreased antioxidative effects of estrogen. These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. The 8-OHdG is one of the main markers of DNA oxidative damage induced by reactive oxygen species (ROS). Objective: We aimed to investigate effects of moderate aerobic training on the ascending aorta of LDL-knockout (LDL-KO) and ovariectomized female mice. Methods: A total of 15 C57BL/6 mice and 15 LDL-KO mice were divided into experimental groups. The thickness and volume density of types I and III collagen fibers were performed by morphoquantitative analysis, whereas the MMP-2 and MMP-9 and 8-OHdG were detected by immunohistochemistry and apoptosis was detected by the TUNEL assay. The significance level for all tests was p < 0.05. Results: Exercise causes an increase in the thickness of the aorta in LDL-KO groups, particularly accentuated in the ovariectomized groups. The type I collagen fibers showed an increase in volume density influenced by training in both Control groups and in the LDL-KO group. Type III collagen density decreased in both groups. The MMP-2 showed moderade immunostaining in the tunica media in LDL-KO groups, which did not occur in the control groups and the MMP-9 stained irregularly in all tissues. The marker 8-OhdG was stronger in the exercise training groups. Additionally, the ovariectomy, the exercise training and the LDL-KO treatments increased apoptosis. Conclusion: These results suggest that moderate-intensity aerobic exercise in ovariectomized mice associated to an increase in LDL rate possibly increases oxidative stress and apoptosis induction.

Resumo Fundamento: Na menopausa, há maior exposição celular ao estresse oxidativo, relacionada à diminuição dos efeitos antioxidantes do estrogênio. Essas alterações metabólicas favorecem a progressão das doenças cardiovasculares, como a aterosclerose. A função anormal da aorta - a artéria mais importante - está associada a muitas doenças cardiovasculares. O colágeno, especialmente os tipos I e III, é um dos mais importantes componentes da parede da aorta e pode ser afetado por muitos fatores, incluindo a menopausa. Por sua vez, 8-OHdG é um dos principais marcadores de danos oxidativos do DNA induzidos por espécies reativas de oxigênio (EROS). Objetivo: Investigar os efeitos do treinamento aeróbico moderado na aorta ascendente de camundongos fêmeas, nocaute para LDL (LDL-KO) e ovariectomizadas. Métodos: Um total de 15 animais C57BL/6 e 15 animais LDL-KO foram divididos em grupos experimentais. A espessura e a densidade de volume das fibras de colágeno tipos I e III foram realizadas por análise morfoquantitativa; MMP-2 e MMP-9 e 8-OHdG foram detectadas por imunohistoquímica; e a apoptose foi detectada pelo ensaio TUNEL. O nível de significância adotado para todos os testes realizados foi p < 0,05. Resultados: o exercício causa aumento da espessura da aorta em grupos LDL-KO, particularmente acentuada em grupos ovariectomizados. As fibras de colágeno de tipo I mostraram aumento da densidade de volume influenciado pelo treinamento em animais controle e LDL-KO. A densidade do colágeno tipo III diminuiu em ambos os grupos. A MMP-2 mostrou imunomarcação moderada na túnica média em animais LDL-KO; em grupos controle, a MMP-9 marcou irregularmente em todos os tecidos. O marcador 8-OHdG foi mais forte nos grupos de treinamento de exercícios. Além disso, a ovariectomia, o treinamento físico e os tratamentos de LDL-KO aumentaram a apoptose. Conclusão: Esses resultados sugerem que exercícios aeróbicos de intensidade moderada em camundongos ovariectomizados associados ao aumento da taxa de LDL, possivelmente, aumentam o estresse oxidativo e a indução da apoptose.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Hiperplasia em túnicas de artérias coronárias de beijupirás criados em sistema offshore / Hyperplasia in tunics of coronary arteries in beijupirá farmed in offshore system

As lesões coronarianas já foram relatadas em espécies de peixes anádromos, com características semelhantes às observadas em aterosclerose humana, mas não em peixes cultivados sem interferência de padrões reprodutivos. Objetivou-se descrever lesões coronarianas em beijupirá (Rachycentron canadum) criado em sistema offshore, em 54 exemplares coletados ao longo do cultivo de oito meses. Amostras de tecido cardíaco de alevinos e juvenis foram submetidas à análise histopatológica e à microscopia eletrônica de transmissão (MET), para visualização de lesões coronarianas, sendo as lâminas histológicas coradas pela técnica de hematoxilina-eosina, ácido periódico de Schiff, alcian blue e reticulina de Gomori. Exames realizados pela fotomicroscopia de luz evidenciaram lesões arteriais caracterizadas por hiperplasia das túnicas íntima e média de artérias coronárias em, respectivamente, 29,63% e 79,63% dos animais, com redução do lúmen arterial. Na MET, foram observadas alterações na estrutura das coronárias com espessamento do endotélio e membrana basal, proliferação de fibroblastos e fibras colágenas, com acúmulo de material lipídico subendotelial, resíduos celulares aderidos à membrana basal e vesículas pinocitóticas com presença de lisossomos isolados. Constatou-se que os peixes da espécie Rachycentron canadum criados em cativeiro desenvolvem lesão arterial do tipo crônica degenerativa inflamatória.

The coronary lesions have been reported in species of anadromous fish with similar characteristics as those observed in human atherosclerosis, but not in farmed fish without interference of reproductive patterns. This study aimed to describe coronary lesions in beijupirá (Rachycentron canadum) farmed in an offshore system, in 54 specimens collected along an eight month cultivation period. Samples of heart tissue of fry and juveniles were subjected to histopathological analysis and transmission electron microscopy (TEM) for visualization of coronary lesions, the histology slides were stained using hematoxylin-eosin, periodic acid Schiffh, alcian blue, and reticulin of Gomori. Examinations performed by light microscopy showed arterial lesions characterized by hyperplasia of the intima and media tunics, respectively in 29.63% and 79.63 % of the animals, with reduced lumen. In TEM changes in the structure of the coronary endothelium and thickening of the basement membrane, proliferation of fibroblasts and collagen fibers, with subendothelial accumulation of lipid material, cellular debris adhering to the basement membrane and presence of pinocytotics vesicles and isolated lysosomes were observed. It has been found that the Rachycentron canadum fish species farmed in captivity develop arterial lesion of the chronic inflammatory degenerative type.

Avaliação da espessura do complexo mediointimal das carótidas em idosos portadores de esclerose valvar aórtica / Evaluation of the carotid intima-media complex thickness in elderly patients with aortic valve sclerosis

Objetivo: Avaliar a medida da ECMIC em idosos portadores de EVAo, de forma a tentar estabelecer uma relação entre a EVAo e a Aterosclerose de Carótidas. Método: Estudo seccional observacional baseado na demanda espontânea do Serviço de Ecocardiografia do Centro Clínico Vingt-un Rosado, município de Mossoró-RN, no período de novembro de 2.009 a junho de 2.010. Foram excluídos com história de evento e/ou doença cardiovascular prévios. Foram considerados portadores de aumento da ECMIC, aqueles que tiveram uma medida da ECMIC ≥ 10mm. A análise estatística foi realizada pelo método do Teste Exato de Fisher, considerando significância estatística para um p < 0,05. Resultados: Foram avaliados 105 pacientes, dos quais 37 preenchiam os critérios de exclusão do estudo. Entre os 68 pacientes analisados, foram 18 (26,4%) homens e 50 mulheres (73,5%), com média de idade de 71,9 anos. 56 pacientes (82,3%) tinham EVAo, sendo 16 do sexo masculino (28,5%) e 40 do sexo feminino (71,4%); e 40 apresentavam aumento da ECMI, com prevalência significativamente maior nos pacientes portadores de EVAo (p < 00,5). Conclusão: Os resultados sugerem que idosos portadores de EVAo devem ser mais bem avaliados para detecção de ateromatose subclínica.

Correlation of lifetime progress of atherosclerosis and morphologic markers of severity in humans: new tools for a more sensitive evaluation

OBJECTIVES: To describe the morphological features of atherosclerosis in the aortas of autopsied patients (ranging from young adults to the elderly), thus providing new tools for a more sensitive morphological evaluation. METHOD: We collected 141 aorta samples. We assessed the macroscopic degree of atherosclerosis, thickness of the intima and media, lipid and collagen depositions in the intima, and the infiltration of mast cells into the layers of the aorta. We correlated the findings with gender, age, race and cause of death. RESULTS: The degree of atherosclerosis was significantly higher in the elderly. The aorta was thicker in the elderly and in cases with a cardiovascular cause of death. The thickness of the intima was significantly greater in the elderly, in males and in cases with a cardiovascular cause of death. The lipid content in the intima of the aorta was significantly higher in Caucasians. Older people and men had a significantly higher number of mast cells. CONCLUSION: A macroscopic evaluation is a good indicator of the severity of atherosclerosis, but a more detailed analysis, namely evaluating the thickness of the layers of the aorta and the number of mast cells, may further elucidate the changes in the constituents of this vessel.

Efeitos da remoção da túnica adventícia da aorta descendente em suínos / Effects of removal of the adventitia of the descending aorta and structural alterations in the tunica media in pigs

OBJETIVO: Investigar os efeitos da remoção da adventícia da aorta em suínos. MÉTODOS: O experimento foi realizado com oito suínos. Removeu-se a camada adventícia da aorta descendente. Após a eutanásia com duas, quatro, seis e oito semanas, o segmento aórtico era removido. Após, eram feitos cortes histológicos com a coloração de hematoxilina e eosina (HE) e pelo método de Weigert - Van Gieson. RESULTADOS: Após duas semanas identificou-se um leve desarranjo do terço externo da túnica média. Nos animais sacrificados após quatro semanas observou-se um desarranjo estrutural dos terços externos da túnica média. Após seis semanas observou-se necrose da parede aórtica. Finalmente, após oito semanas além da fibrose da parede aórtica identificou-se a destruição da lâmina elástica interna. CONCLUSÃO: A remoção da adventícia da aorta em suínos levou à alterações degenerativas da média, determinando perda da estrutura da parede aórtica que é variável em sua localização, intensidade e forma, dependendo do tempo a partir do qual se estabeleceu a lesão isquêmica.

OBJECTIVE: To investigate the effects of removal of the adventitia on the tunica media in a pig model. METHODS: The experiment was performed in eight pigs. The adventitia of the descending aorta was removed. Following euthanasia, at two, four, six and eight weeks, the aortic segment was removed. Next, slices of the aorta were stained with hematoxylin and eosin (HE) and Weigert - Van Gieson. RESULTS: After two weeks there was a slight cellular breakdown in the outer third of the media. After four weeks structural breakdown of elastic fibers was observed in the outer two thirds of the same layer. In six weeks, several areas of necrosis and almost complete disruption of elastic fibers were identified. Finally, after eight weeks, there was fibrosis of the entire wall with disruption of the internal elastic lamina. CONCLUSION: The removal of the adventitia leads to degeneration of the media, determining loss of the normal structure of the aortic wall that is variable in its location, intensity and shape, depending on the length and duration of the ischemic insult.

Carotid intima-media thickness correlation with lipid profile in patients with familial hypercholesterolemia versus controls

To determine the variations in carotid intima-media thickness [CIMT] in familial hypercholesterolemia [FH] patients and its use as predictive marker for premature cardiovascular diseases. National Institute of Cardiovascular Diseases and Dr. Ziauddin Hospital, Karachi, from June 2008 to October 2009. Familial hypercholesterolemia was clinically diagnosed by premature coronary diseases, xanthomas, arcus cornealis and family history of premature coronary heart diseases. Controls were age matched normal individuals without hypercholesterolemia. Their lipid profile was tested after overnight fasting. CIMT was measured in mm using B-mode ultrasonography using linear probe. Student t-test was applied to compare mean CIMT of cases and the control. The mean CIMT values of the FH cases were correlated with LDL using Pearson's correlation test. Forty cases with hypercholesterolemia gave consent to participate in the study. These patients had total cholesterol >200 mg/dL and LDL >/= 160 mg/dL as compared to twenty controls of similar age with total cholesterol

Arterial Stiffness is Associated With Diabetic Retinopathy in Korean Type 2 Diabetic Patients / 예방의학회지

OBJECTIVES: We evaluated the association between common carotid artery intima-media thickness (CCA-IMT), brachial-ankle pulse wave velocity (baPWV), carotid plaque, and peripheral arterial disease (PAD) as indicators of macroangiopathy and diabetic retinopathy as an indicator of microangiopathy in type 2 diabetic patients. METHODS: We analyzed 605 type 2 diabetic patients registered at a public health center in Korea. Following overnight fasting, venous blood and urine samples were collected and analyzed. The CCA-IMT, levels of carotid plaque, baPWV, and ankle-brachial index (ABI) of the subjects were assessed. We used non-mydriatic fundus photography to diagnose diabetic retinopathy. Multiple logistic regression analyses were used to evaluate the association between macroangiopathy and diabetic retinopathy. CCA-IMT and baPWV were divided into tertiles: CCA-IMT, 0.39 to 0.65 mm, 0.66 to 0.78 mm, and 0.79 to 1.30 mm; baPWV, 9.9 to 15.8 m/s, 15.9 to 18.9 m/s, and 19.0 to 38.0 m/s. RESULTS: The association between baPWV and diabetic retinopathy remained significant after adjustment, with an increasing odds ratio (OR) in the second tertile (OR, 2.41; 95% confidence interval [CI], 1.27 to 4.55) and the third tertile (OR, 4.63; 95% CI, 2.33 to 9.21). No significant differences were observed in carotid plaque, PAD, and each tertile of CCA-IMT. CONCLUSIONS: BaPWV was associated with diabetic retinopathy, while CCA-IMT, carotid plaque, and PAD were not. This study suggests that the association between macroangiopathy and microangiopathy may be attributable to functional processes rather than structural processes within the vascular system.

Correlation between Hyperghrelinemia and Carotid Artery Intima-Media Thickness in Children with Prader-Willi Syndrome

PURPOSE: Prader-Willi syndrome (PWS) is a genetic disorder characterized by childhood-onset obesity and endocrine dysfunction that leads to cardiovascular disability. The objective of the study is to assess the relationship between carotid intima-media thickness (IMT) and atherosclerotic risk factors. MATERIALS AND METHODS: Twenty-seven PWS children and 24 normal controls were enrolled. Correlations of IMT with atherosclerotic risk factors were assessed. RESULTS: IMTs in the PWS group did not differ from those in the controls (p = 0.172), although total ghrelin levels were higher in the PWS children (p = 0.003). The multivariate analysis revealed positive correlations between total ghrelin levels (rho = 0.489, p = 0.046) and IMT in the PWS group and between body mass index-standard deviation score (BMI-SDS) (rho = 0.697, p = 0.005) and IMT in the controls. CONCLUSION: Considering the positive correlation of IMT with total ghrelin levels and the high level of ghrelin in PWS children, a further study is warranted to evaluate the role of elevated ghrelin on atherosclerosis for PWS.

Association Between Meat Consumption and Carotid Intima-Media Thickness in Korean Adults with Metabolic Syndrome / 예방의학회지

OBJECTIVES: The effect of meat consumption on cardiometabolic risk has been continuously studied, but their associations are not conclusive. The aim of this study is to examine the association between the consumption of meat or red meat and carotid intima-media thickness (IMT) in healthy Korean adults. METHODS: This study evaluated 2374 community-dwelling adults (933 men and 1441 women) who were free of cardiovascular disease or cancer, living in a rural area in Korea. Total meat and red meat intakes were assessed with a validated 103 item-food frequency questionnaire. Carotid IMT was evaluated ultrasonographically, IMTmax was defined as the highest value among IMT of bilateral common carotid arteries. RESULTS: After adjustment for potential confounding factors, the mean IMTmax tended to increase in higher meat consumption groups in both men and women with metabolic syndrome (p for trend= 0.027 and 0.049, respectively), but not in participants without metabolic syndrome. Frequent meat consumption (> or =5 servings/week) was significantly associated with higher IMTmax in men with metabolic syndrome (by 0.08 mm, p=0.015). Whereas, the association was not significant in women (by 0.05 mm, p=0.115). Similar but attenuated findings were shown with red meat intake. CONCLUSIONS: Our findings suggest that a higher meat consumption may be associated with a higher carotid IMT in Korean adults with metabolic syndrome. The frequent meat consumption (> or =5 servings/week), compared with the others, was associated with a higher carotid IMTmax only in men with metabolic syndrome. Further research is required to explore optimal meat consumption in people with specific medical conditions.

Modificación del grosor intima-media carotídeo según factores de riesgo clásicos y síndrome metabólico con o sin inflamación / Relation of intima-media thickness, traditional risk factors and metabolic syndrome in subjects with or without inflammation

El grosor intima-media carotideo (CIMT) es un marcador de aterosclerosis subclinica y eventos isquémicos cerebrales y coronarios. Si bien los valores normales promedio en Chile, han sido publicados, no existen datos locales de cómo se modifica el CIMT según la carga de factores de riesgo (FR) cardiovascular. Objetivos: Analizar la modificación del CIMT según la carga de FR clásicos, presencia de síndrome metabólico (SMET) y SMET más inflamación. Métodos: Hombres y mujeres de Santiago sin antecedente de eventos isquémicos previos, nivel socio económico medio, medio bajo y medio alto. En todos se realizó encuesta sobre antecedentes demográficos, FR cardiovascular, y medición de PA, IMC, cintura, y perfil lipídico, glicemia y proteína C-reactiva ultrasensible (ePCR) en ayuno. Para diagnóstico de SMET se usó NCEP ATPIII (2001), y para inflamación, ePCR> 2 mg/L (valor de corte de > riesgo porAHA). El CIMT se midió en carótida común derecha e izquierda con software MATH®. Resultados: Se incluyeron en el análisis 999 sujetos (508 hombres), edad promedio 43.8 +/- 11 años. La prevalencia de HTA fue 30 por ciento, dislipidemia 68 por ciento, tabaquismo 47 por ciento, y SMET 24 por ciento. El CIMT medio promedio fue 0.61 +/- 0.1 mm y la ePCR promedio 2.22 mg/L. La modificación del CIMT medio (mm) según número de FR (edad>45/55 hombre/mujer, diabetes, HTA, colesterol total > 200, HDL < 40/50, tabaquismo e historia familiar), fue la siguiente: 0 FR= 0.55 +/- 0.08; 1-2 FR= 0.59 +/- 0.091; > 3 FR= 0.67 +/- 0.12 (p < 0.0001). Asimismo, el CIMT aumentó según el puntaje de Framingham: < 5 por ciento = 0.58 +/- 0.09; 5-10 por ciento= 0.66 +/- 0.11; > 10-20 por ciento= 0.68 +/- 0.11; >20 por ciento > o = 0.76 +/- 0.14 (p < 0.0001). El CIMT fue significativamente mayor en los sujetos con SMET, y se incrementa en forma significativa cuando se adiciona ePCR>2 mg/L. En el modelo de regresión múltiple, el CIMT se asocia en forma conjunta a Framingham (p < 0.0001) y SMET+ePCR>2...

Carotid intima-media thickness (CIMT) is a marker for cerebral and coronary ischemic events. Normal values for CIMT in Chile have been published but the relation of CIMT to level of risk factors (RF) is unknown. Aim. To analyze the relation of CIMT to level of traditional RF and the presence of metabolic syndrome (MS), with or without inflammation. Methods. Males and females living in Santiago, Chile, with no prior history of ischemic events, of a low, medium or high socio-economic level, were studied. Demographic data, and presence of RF were obtained. Blood pressure, BMI, waist, blood lipids, blood glucose and US-CRP were measured in the fasting state. The presence of MS was defined by the NCEP-ATP III (2001) criteria. Inflammation was defined as US-CRP >2mg/L (the cut off point for increased risk, according to the AHA). CIMT was measure in both carotid arteries using the MATH® software. Results. 999 subjects (508 males), aged 43 +/- 11 years old. The prevalence of hypertension (HT) was 30 percent, dyslipidemia 68 percent, tobacco use 41 percent and MS 24 percent. Mean CIMT was 0.61 +/- 0.1 mm and US-PCR was 2.22 mg/L. CIMT according to number of RF - age > 45/55 (male/female), diabetes, HT, total cholesterol > 200 mg/dl, HDL < 40/50 mg/dl, tobacco use and family history- were: 0 RF: 0.55 +/- 0.08; 1-2 RF: 0.59 +/- 0.091; >3 RF: 0.67 +/- 0.12 (p < 0.0001). CIMT according to Framingham scores was: < 5 percent: 0.58 +/- 0.09; 5 - 10 percent: 0.66 +/- 0.11; 10 - 20 percent: 0.68 +/- 0.11 and > 20 percent: 0.76 +/- 0.14 (p < 0.0001). CIMT was significantly greater in subjects with MS and more in the group with US-PCR > 2mg/L. In multiple regression analysis, CIMT was jointly associated to Framingham score (p < 0.0001) and presence of MS + US-PCR >2 mg/L (p=0.01) (r2=0.19 for the model). Conclusion. CIMT increases in relation to traditional RF load and the presence of MS. An increased atherosclerotic risk in subjects with MS+inflammation (US-PCR > 2 mg/L)...

Complexo miointimal das carótidas comum e interna em portadores de esquistossomose mansônica hepatoesplênica / Intima-media thickness of common and internal carotid arteries in patients with hepatosplenic schistosomiasis mansoni

OBJETIVO: Avaliar a espessura do complexo miointimal (IMT) das carótidas comum e interna, em portadores de esquistossomose hepatoesplênica (EHE) não tratados cirurgicamente, já submetidos a cirurgia para descompressão do sistema porta por esplenectomia e ligadura da veia gástrica esquerda, e comparar com volutários de condições sócio-econômico-ambientais similares, não portadores de esquistossomose. MÉTODOS: Utilizando aparelho de ultra-som Doppler de 7,5MHz foram mensurados os IMT de três grupos de voluntários, de ambos os gêneros, com idades que variaram de 20 a 60 anos, sendo avaliados os IMT máximos, IMT médios, IMT mínimos e seus desvios-padrão, das carótidas comuns e internas e feitas as comparações entre os grupos e suas associações com fatores de risco: idade, hipertensão arterial e tabagismo. RESULTADOS: Não houve diferença significante na média dos IMT, entre os lados direito e esquerdo e nem entre os grupos. Nos pacientes tratados cirurgicamente, assim como nos indivíduos-controle confirmou-se a associação, já conhecida, com os fatores de risco para aterosclerose (idade, hipertensão arterial e tabagismo). Contudo, não se observou este comportamento nos pacientes não operados. CONCLUSÃO: A EHE sem tratamento cirúrgico parece conferir "alguma proteção" contra a aterogênese em seres humanos; todavia, os achados não dão suporte definitivo a esta hipótese.

OBJECTIVE: To evaluate the intima-media thickness (IMT) of common and internal carotid arteries in patients with hepatosplenic schistomiasis mansoni and those who underwent portal decompression surgery (splenectomy and left gastric artery ligature). Both groups were compared with a health volunteer control group, living in the same social-economic-environmental conditions. MEHTODS: An ultrasound Doppler with a 7.5 MHz probe was used. The IMT was measured in the three groups with 20 individuals each, of both gender, with ages ranging from 20 to 60 years. The mean and standard deviations of common and internal carotid arteries maxIMT, medIMT, minIMT were assessed. Risk factors: age, systemic arterial hypertension and cigarette smoking were investigated as regard to IMT measurements. RESULTS: There were no statistical differences in IMT between right and left side, and among surgical, non-surgical and control groups. The surgical treated patients and controls showed correlation to known atherosclerotic risk factors: age, hypertension and cigarette smoking. However, non-surgically treated patients did not present the same correlation. CONLCUSION: It is tempting to believe that non-operated schistosomotic patients may have "some protection" against atherogenesis in human beings; however, the data do not lend full support to this hypothesis.

Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism

Subclinical hypothyroidism (SHT) is a disease for which exact therapeutic approaches have not yet been established. Previous studies have suggested an association between SHT and coronary heart disease. Whether this association is related to SHT-induced changes in serum lipid levels or to endothelial dysfunction is unclear. The aim of this study was to determine endothelial function measured by the flow-mediated vasodilatation of the brachial artery and the carotid artery intima-media thickness (IMT) in a group of women with SHT compared with euthyroid subjects. Triglycerides, total cholesterol, HDL-C, LDL-C, apoprotein A (apo A), apo B, and lipoprotein(a) were also determined. Twenty-one patients with SHT (mean age: 42.4 ± 10.8 years and mean thyroid-stimulating hormone (TSH) levels: 8.2 ± 2.7 µIU/mL) and 21 euthyroid controls matched for body mass index, age and atherosclerotic risk factors (mean age: 44.2 ± 8.5 years and mean TSH levels: 1.4 ± 0.6 µIU/mL) participated in the study. Lipid parameters (except HDL-C and apo A, which were lower) and IMT values were higher in the common carotid and carotid bifurcation of SHT patients with positive serum thyroid peroxidase antibodies (TPO-Ab) (0.62 ± 0.2 and 0.62 ± 0.16 mm for the common carotid and carotid bifurcation, respectively) when compared with the negative TPO-Ab group (0.55 ± 0.24 and 0.58 ± 0.13 mm, for common carotid and carotid bifurcation, respectively). The difference was not statistically significant. We conclude that minimal thyroid dysfunction had no adverse effects on endothelial function in the population studied. Further investigation is warranted to assess whether subclinical hypothyroidism, with and without TPO-Ab-positive serology, has any effect on endothelial function.

Comparison of common carotid artery intima-media thickness between Brazilian Euro-descendants and Afro-descendants with atherosclerosis risk factors

OBJECTIVE: To compare common carotid intima-media thickness (IMT) between the two major Brazilian ethnic groups (those of African descent and those of European descent) among individuals with one or more risk factors for atherosclerotic disease. METHOD: Two hundred and six patients with one or more risk factors for atherosclerotic disease were evaluated in a cross-sectional study in which their clinical, ethnic and Demographic characteristics were collected. All patients underwent duplex ultrasound examination of their carotid vessels to obtain IMT measurements. RESULTS: One hundred and fifty-three patients (74.3%) had a carotid IMT greater than 1.0 mm at one or more point of measurement in at least one common carotid artery. There was a significant correlation between older age and mean carotid wall thickness (R=0.479 / P<0.01). Multivariate analysis identified male sex, arterial hypertension and older age as variables associated with increased IMT (P<0.05 for all variables). When IMT was compared between the two ethnic groups in this study, no significant differences were noted. Euro-descendants and Afro-descendants had similar IMT values, even when the groups were stratified by degree of IMT (normal vs. increased) and presence of stroke and/or transient ischemic attack (yes vs. no). CONCLUSIONS: The risk factors associated with increased common carotid artery IMT in Brazilian individuals are similar to those in previously described populations. No differences were observed between the two main Brazilian ethnic groups. Longitudinal studies are required for a better evaluation of the incidence, etiologic factors and evolution of carotid intimomedial thickening in this population.

C-reactive Protein and Carotid Intima-media Thickness in a Population of Middle-aged Koreans / 예방의학회지

OBJECTIVES: This study was performed to evaluate the relationship between C-reactive protein (CRP) and carotid intima-media thickness (carotid IMT) in a population of middle-aged Koreans. METHODS: A total of 1,054 men and 1,595 women (aged 40-70 years) from Kanghwa County, Korea, were chosen for the present study between 2006 and 2007. We measured high-sensitivity CRP and other major cardiovascular risk factors including anthropometrics, blood pressure, blood chemistry, and carotid ultrasonography. Health related questionnaires were also completed by each study participant. Carotid IMT value was determined by the maximal IMT at each common carotid artery. The relationship between CRP level and carotid IMT was assessed using multiple linear and logistic regression models after adjustment for age, body mass index, menopause (women), systolic blood pressure, total/HDL cholesterol ratio, triglyceride level, fasting glucose, smoking, and alcohol consumption. RESULTS: Mean carotid IMT values from the lowest to highest quartile of CRP were 0.828, 0.873, 0.898, and 0.926 mm for women (p for trend<0.001), and 0.929, 0.938, 0.949, and 0.979 mm for men (p for trend=0.032), respectively. After adjustment for major cardiovascular risk factors, the relationship between CRP and carotid IMT was significant in women (p for trend=0.017), but not in men (p for trend=0.798). Similarly, adjusted odds ratio of increased IMT, defined as the sex-specific top quartile, for the highest versus lowest CRP quartiles was 1.55 (95% CI=1.06-2.26) in women, but only 1.05 (95% CI=0.69-1.62) in men. CONCLUSIONS: CRP and carotid IMT levels appear to be directly related in women, but not in men.

Association of Abdominal Obesity with Atherosclerosis in Type 2 Diabetes Mellitus (T2DM) in Korea

The aim of this study was to investigate the relationship between obesity, insulin resistance and atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Total 530 patients with T2DM were included. To evaluate the severity of atherosclerosis, we measured the coronary artery calcification (CAC) score, intima-media thickness (IMT) of the common carotid artery, and the ankle-brachial pressure index (ABPI). Subjects were classified according to body mass index (BMI), a marker of general obesity, and waist-to-hip ratio (WHR), a marker of regional obesity. The insulin sensitivity index (ISI) was measured by the short insulin tolerance test. All subjects were classified into four groups, according to BMI: the under-weight group, the normal-weight (NW) group, the over-weight (OW) group, and the obese (OB) group. WHR and systolic blood pressure, triglycerides (TG), HDL-cholesterol (HDLC), free fatty acids (FFA), fibrinogen, and fasting c-peptide levels were significantly different between BMI groups. TG, HDL-C, FFA, fibrinogen and ISI were significantly different between patients with and without abdominal obesity. In the OW group as well as in the NW group, carotid IMT, ABPI and CAC score were significantly different between patients with and without abdominal obesity. This study indicates that abdominal obesity was associated with atherosclerosis in T2DM patients.

A practical protocol to measure common carotid artery intima-media thickness

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement

BACKGROUND/AIMS: Behcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis. We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. METHODS: We studied 40 patients (24 males, mean age: 39.1+/-8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2+/-5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. RESULTS: The carotid IMT in the BD group was significantly higher than that in the control group (0.71+/-0.22 mm vs. 0.59+/-0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85+/-0.21 mm vs. 0.64+/-0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. CONCLUSIONS: Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.

Intima-Media Thickness and Pulse Wave Velocity in Hypertensive Adolescents

Increased intima-media thickness (IMT) and pulse wave velocity (PWV) are noninvasive markers of early arterial wall alteration and are more widely used in adult clinical research. We investigated whether IMT and PWV are useful predictors of cardiovascular risk in hypertensive adolescents. Fifteen hypertensive adolescents (13-18 yr old, systolic BP > or = 140 mmHg, diastolic BP > or = 90 mmHg) and seventeen normotensive subjects were included. Height, weight, obesity index, body mass index (BMI), and fat distribution were obtained from each group. Serum lipid, insulin, vitamine B12, folate, renin, aldosterone, angiotensin-converting enzyme (ACE), and homocysteine levels were compared. The carotid IMT and PWV were measured. Arterial wall compliance and distensibility were calculated with the equation. High systolic blood pressure significantly correlated with height, weight, BMI, obesity index, arm circumference, fat mass, and fat distribution. Hypertensive adolescents had significantly greater cIMT (carotid intima-media thickness) and lower elastic properties such as cross-sectional compliance and distensibility of the carotid artery. The carotid IMT significantly correlated with brachial-ankle PWV. In conclusion, the measurement of carotid IMT and brachial-ankle PWV might be useful to predict the development of atherosclerosis in hypertensive adolescents.