Placas ateroscleróticas podem ser estáveis ou vulneráveis à formação de trombo, e os dois processos mais comumente envolvidos a este grave desfecho de trombose luminal são ruptura e erosão de placa. O conhecimento deste estado de vulnerabilidade pode ser importante na prática clínica. A parede arterial é um importante local de modificação proteica em resposta ao estresse. Proteínas em placas ateroscleróticas podem ser nitradas e seu acúmulo durante a aterogênese pode estar relacionado à captação de lipídios. Entre as consequências da nitração proteica, um importante marcador de estresse oxidativo, estão alterações na estrutura, atividade e susceptibilidade a proteólise e estas mudanças podem estar relacionadas a estabilidade da placa. Assim, este estudo teve como objetivo a quantificação e a verificação da distribuição tecidual de proteínas nitradas em segmentos de diferentes graus de vulnerabilidade de um mesmo indivíduo, e a correlação destes marcadores com o perfil histopatológico da placa. Segmentos de diferentes ramos coronários de 30 indivíduos, após infarto agudo do miocárdio fatal, foram estudados. Cinco tipos de placas ateroscleróticas de cada indivíduo foram selecionados, considerando o percentual de estenose e a presença ou não de trombo. Proteínas nitradas totais, linfócitos e macrófagos foram avaliados pela técnica de imuno-histoquímica. Os segmentos apresentando ruptura de placa demonstraram maior número de linfócitos e macrófagos nas camadas adventícia e íntima quando comparados a outros segmentos. A nitração estava relacionada com marcadores histológicos de vulnerabilidade da placa. Além disso, proteínas nitradas estavam diferentemente distribuídas nas camadas do vaso e altos níveis destas proteínas não foram implicados em todos os casos de formação de trombo, já que foi detectado em maior quantidade somente em rupturas de placa e não em casos de erosão de placa. Estes resultados mostram que estresse oxidativo é um importante atributo na diferenciação destes estados patológicos / Atherosclerotic plaques may be stable or vulnerable to thrombus formation. The two processes most commonly involved in this serious outcome of luminal thrombosis are rupture and erosion of the plaque. The knowledge of this vulnerable state of the plaque could be important in clinical practice. The artery wall is an important site of protein modification in response to stress. Proteins in atherosclerotic plaques may be nitrated, and its accumulation during atherogenesis may be related to lipid uptake. The consequences of protein nitration, an important marker of oxidative stress, are changes in its structure, activity and susceptibility to proteolysis and these changes may be related to plaque stability. Thus, this study aimed to quantify and investigate tissue distribution of nitrated proteins in coronary segments of different degrees of vulnerability from the same individual, and correlate these markers with plaque histopathological profile. Segments of coronary branches from 30 patients (after fatal acute myocardial infarct) were studied. Five different types of coronary atherosclerosis plaques from each subject were selected, considering the stenosis percentage and the presence or not of thrombus. Total nitrated protein, lymphocytes and macrophages were assessed by immunohistochemistry. The group presenting disrupted plaque exhibits higher macrophages and lymphocytes content in adventitia an intima layer when compared with other segments. Nitration was related with histological markers of plaque vulnerability. Furthermore, protein nitration was differently distributed in arteries layers and high levels of nitrated proteins were not implicated in all cases of thrombus formation, since it was detected in higher amounts only in ruptured and not in eroded plaques. These findings demonstrates that oxidative stress is an important characteristic in the differentiation of these pathophysiologic states

Fundamentos: Ensaios prévios reunindo pacientes em series consecutivas ou randomicas sem cegamento evidenciaram beneficio da adição do cilostozol à terapia antiplaquetária em diabéticos submetidos ao implante de stents coronários farmacológicos com redução nas taxas de reestenose binária, perda tardia intra-stent e revascularização tardia da lesão alvo. Objetivos: O objetivo primário deste estudo foi verificar se a adição do cilostazol à dupla terapia antiplaquetária, proporcionaria uma redução adicional da hiperplasia intimal em diabéticos após o implante de stent farmacológico, mensurada por meio do cálculo do volume de obstrução pelo ultrassom intracoronário 9 meses após o procedimento índice. Os objetivos secundários foram aferir a angiografia quantitativa do vaso alvo e ocorrência de eventos cardíacos adversos graves (óbito, infarto do miocárdio não fatal e necessidade de nova revascularização da lesão-alvo) aos 30 dias, 9 meses e 1 ano. Casuística e métodos: Estudo prospectivo, unicêntrico, randomizado, duplo cego, reunindo 133 pacientes diabéticos, comparando pacientes que receberam cilostazol (Grupo 1, n= 65 ) versus placebo (Grupo 2, n= 68), submetidos a implante de stent coronário com liberação de zotarolimus em artéria coronária nativa com estenose maior ou igual a 50% e diâmetro de referência igual ou superior a 2,0 mm (avaliação visual), com reestudo angiográfico e análise ultrassonográfica aos 9 meses. Resultados: Os 2 grupos foram similares nas características clínicas, angiográficas e técnicas, exceto na evidencia de maior incidência de hipertensão arterial no grupo 2 (81,5% vs 94,1%, p=0,026) assim como nos diâmetros dos stents coronários utilizados, significativamente menores no grupo 1 (2,78 mm vs 2,96 mm, p<0,001). O calculo do volume de obstrução intimal por meio do ultrassom intracoronário aos 9 meses foi similar entre os grupos (33,2% vs 35,1%, p=0,069), assim como as taxas de eventos cardíacos adversos graves (12,3% vs 8,8%, p= 0,811), trombose de stent (1,5% versus 0,75%, p= 0,237), reestenose binária intra-sent (9,8% vs 6,8%, p= 0,988), perda tardia intra-stent (0,60 vs 0,64, p=0,300) e no segmento ( 0,57 vs 0,58, p= 0,387). Conclusões: A adição do cilostazol à dupla terapia antiplaquetária com ácido acetilsalicílico e clopidogrel em pacientes diabéticos submetidos à implante de stent com zotarolimus, não reduziu eventos cardíacos adversos graves ou o porcentual de hiperplasia intimal intra-stent mensurado pela análise volumétrica do ultrassom intracoronário. / Background: Previous trials with assembled patients in consecutive or random series without blindness offered evidence of the benefit adding cilostazol to the antiplatelet therapy in diabetic patients undergoing drug-eluting stents coronary implantation, with reduction in binary restenosis rates, in-stent late loss and late target lesion revascularization. Objectives: The primary objective of this study was to determine whether the addition of cilostazol to the dual antiplatelet therapy would provide an additional intimal hyperplasia reduction in diabetic patients after drug-eluting stents implantation, measured by calculating the obstruction volume through the intravascular ultrasound 9 months after the index procedure. Secondary objectives were to assess the target vessel quantitative angiography and the occurrence of serious adverse cardiac events (death, nonfatal myocardial infarction and need for a target lesion revascularization) at 30 days, 9 months and 1 year. Methods: Prospective, single center, randomized, double blinded study, gathering 133 diabetic patients, comparing who received cilostazol (Group 1, n= 65) versus placebo (Group 2, n= 68), undergoing coronary stenting, with the releasing of zotarolimus in a native coronary artery with stenosis greater than or equal to 50% and reference diameter equal to or greater than 2.0 mm (visual assessment) with the intravascularultrasound and angiographic restudy at 9 months. Results: Both groups were similar in clinical, angiographic and technical characteristics, except for a higher incidence of arterial hypertension in group 2 (81,5% vs 94,1%, p=0,026) as well as significantly lower coronary stents diameters in group 1 (2,78 mm vs 2,96 mm, p<0,001). The intimal obstruction volume calculated by the intravascularultrasound at 9 months was similar between the groups (33,2% vs 35,1%, p=0,069), as well as the rates of major adverse cardiac events (12,3% vs 8,8%, p= 0,811), stent thrombosis (1,5% versus 0,75%, p= 0,237), in-stent binary restenosis (9,8% vs 6,8%, p= 0,988), in stent late loss (0,60 vs 0,64, p=0,300) and at the segment ( 0,57 vs 0,58, p= 0,387). Conclusions: The addition of cilostazol to the dual antiplatelet therapy with acetylsalicylate acid and clopidogrel, in diabetic patients undergoing stent implantation with zotarolimus did not reduce major adverse cardiac events nor the percentage of intra-stent intimal hyperplasia measured by the intravascularultrasound volumetric analysis.

A terapia antiagregante é comumente indicada na prevenção e tratamento de doenças cardiovasculares. A dupla antiagregação com clopidrogrel e ácido acetilsalicílico (AAS) tem sido frequentemente adotada em pacientes com Doença Arterial Coronariana (DAC), mas apresenta ineficácia em uma parcela significativa da população com genótipo de respondedores. Essa falha terapêutica nos leva a questionar se outros mecanismos moleculares podem estar influenciando na resposta a esses fármacos. Recentes estudos sugerem que pequenas sequências de RNA não codificantes denominadas microRNAs (miRNAs) podem estar fortemente relacionadas com resposta ao tratamento fármaco-terapêutico, controlando as proteínas envolvidas na farmacocinética e farmacodinâmica. Entretanto, os principais miRNAs que atuam na dinâmica da resposta medicamentosa ainda não foram bem definidos. O objetivo deste estudo foi avaliar o perfil de miRNAs no sangue total periférico, procurando melhor esclarecer os mecanismos envolvidos na resposta aos antiagregantes plaquetários AAS e clopidogrel. Para isso, selecionou-se pacientes com DAC, os quais apresentavam diferentes respostas à dupla terapia de antiagregação determinadas pelo teste de agregação plaquetária. Baseados nos fenótipos, os perfis de expressão de miRNAs foram comparados entre os valores da taxa de agregação categorizados em tercis (T) de resposta. O grupo T1 foi constituído de pacientes respondedores, o T2 de respondedores intermediários e o T3 de não respondedores. Os perfis de miRNAs foram obtidos após sequenciamento de última geração e os dados obtidos foram analisados pelo pacote Deseq2. Os resultados mostraram 18 miRNAs diferentemente expressos entre os dois tercis extremos. Dentre esses miRNAs, 10 deles apresentaram importantes alvos relacionados com vias de ativação e agregação plaquetária quando analisados pelo software Ingenuity®. Dos 10 miRNAs, 4 deles, os quais apresentaram-se menos expressos no sequenciamento, demonstraram os mesmos perfis de expressão quando analisados pela reação em cadeia pela polimerase quantitativa (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR- 30a-5p e hsa-let-7g-5p. A partir das análises de predição de alvos, pôde-se observar que os quatro miRNAs, quando menos expressos simultaneamente, predizem ativação da agregação plaquetária. Além disso, os miRNAs hsa-miR- 423-5p, hsa-miR-744-5p e hsa-let-7g-5p mostraram correlação com o perfil lipídico dos pacientes que, por sua vez, apresentou influência nos valores de agregação compreendidos no T3 de resposta a ambos os medicamentos. Sendo assim, conclui-se que maiores taxas de agregação plaquetária podem estar indiretamente relacionadas com os padrões de expressão de hsa-miR- 423-3p, hsa-miR-744-5p e hsa-let-7g-5p. Sugere-se que a avaliação do perfil de expressão destes 3 miRNAs no sangue periférico de pacientes com DAC possa predizer resposta terapêutica inadequada ao AAS e ao clopidogrel / The antiplatelet therapy is often indicated for the prevention and treatment of cardiovascular diseases. Dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) has often been adopted in patients with coronary artery disease (CAD), but it has been ineffective in a significant portion of the population with genotype of responders. This fact leads us to question whether other molecular mechanisms may be influencing the response to these drugs. Recent studies suggest that small non-coding RNA sequences known as microRNAs (miRNAs) may be closely related to response to drug-therapeutic treatment, controlling proteins involved in pharmacokinetics and pharmacodynamics. The aim of this study was to evaluate the profile of miRNAs in whole blood, looking to better clarify mechanisms involved in ASA and clopidogrel response. For this purpose, we selected CAD patients who showed different responses to dual antiplatelet therapy determined by aggregation test. Based on the phenotypes, the miRNA expression profiles were compared between the platelet aggregation values categorized into tertiles (T) of response. The T1 group consisted of responding patients, the T2 consisted of intermediate responders and the T3 consisted of non-responders. The miRNA profiles were obtained after next-generation sequencing and data were analyzed by Deseq2 package. Results showed that 18 miRNAs were differentially expressed between the two extreme tertiles. By Ingenuity® software prediction analysis, 10 miRNAs showed important targets related with activation and aggregation of blood platelets. Of the 10 miRNAs, 4 of them, which were down-expressed on sequencing, showed the same fold-regulation when expression profiles were analyzed by quantitative polymerase chain reaction (qPCR): hsa-miR-423-3p, hsa-miR-744-5p, hsa-miR-30a-5p and has-hsa- let-7g-5p. By target prediction analysis, it was observed that, when the four miRNAs are simultaneously down-expressed, they predict activation of platelet aggregation. Furthermore, hsa-miR-423-5p, hsa-miR-744-5p, and hsa-let-7g-5p showed correlation with the lipid profile of patients which, in turn, demonstrated influence in aggregation values reaching T3 of response to both drugs. Therefore, we concluded that increased platelet aggregation rates may be indirectly related to the expression profiles of hsa-miR-423-3p, hsa-miR-744-5p and hsa-let-7g-5p. It is suggested that the evaluation of the expression profile of these three miRNAs in the peripheral blood of patients with CAD may predict inadequate therapeutic response to aspirin and clopidogrel.

Made available in DSpace on 2016-08-19T18:15:56Z (GMT). No. of bitstreams: 1 Jose Bonifacio Barbosa.pdf: 454904 bytes, checksum: 58dc9e9d8bdd68d23658064050114df3 (MD5) Previous issue date: 2008-11-11 / The metabolic syndrome (MS) is responsible for increasing cardiovascular morbidity and mortality in the entire world. However, it remains as a complex entity because it has no clear definition and also by the lack of uniformity in the diagnostic criteria. Thus, there are many controversies regarding its exact prevalence in non-selected populations and few studies performed in cardiology outpatient clinic, where the population presents multiple risk factors and the MS can be an aggravating finding determining changes in the therapeutical strategies. The purpose of this research were: to determine the prevalence of MS according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) and the International Diabetes Federation (IDF), to evaluate the differences of the prevalence in both sex, to establish the correlation of MS and other risk factor and cardiovascular diseases (CVD), and to analyze the concordance between the two methods by Kappa. The prevalence was 54.4% and 63.6% according to the NCEP ATPIII and IDF respectively. Considering the gender, the prevalence was higher in female (59%) by the criteria of the NCEP ATPIII. Coronary artery disease (CAD) presented higher frequency among patients with MS (28.4% NCEP ATPIII and 24.3% IDF, p<0.001), but this correlation was not seen among those who had stroke. Age > 40 years and body mass índex (BMI) > 30kg/m² were the variables more frequently associated with a greater risk of MS (p<0,001) after the adjusted analysis of risk factors by the IDF criteria. The general concordance between the two criteria was 0.70 (p<0.001), which was higer in female, 0.82 than in male, 0.85. In conclusion, the prevalence of MS in cardiology outpatient clinic is higher than for the general population with predominance of female sex by the NCEP ATPIII and it has been associated with CAD. There was a good concordance of the two methods used to evaluate the MS; wich was great for the female sex and just regular for male, suggesting that criteria currently utilized for the diagnosis of MS are not adequate for the male sex. It is likely that the cut-off of the waist circunference utilized by the IDF has been responsible for the low concordance found in the female sex by the two definitions. / A síndrome metabólica (SM) é responsável pelo aumento da morbimortalidade cardiovascular em todo o mundo. Porém, permanece como um transtorno complexo por não ter uma definição claramente estabelecida e pela falta de uniformidade dos seus critérios diagnósticos. Desse modo, há muitas divergências quanto à sua exata prevalência em populações não selecionadas, e há poucos relatos de estudos realizados em ambulatórios especializados em cardiologia, onde a população apresenta múltiplos fatores de risco e a presença da SM poderá ser um agravante, determinando mudanças nas estratégias terapêuticas. Os propósitos desta pesquisa foram: determinar as prevalências da SM de acordo com os critérios do National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) e International Diabetes Federation (IDF), avaliar as diferenças na prevalência entre os sexos, verificar a associação entre SM e outros fatores de risco e doenças cardiovasculares (DCVs) e analisar a concordância entre os dois métodos pelo Kappa. A prevalência foi de 54,4% pelo NCEP ATPIII e 63,6% pelo IDF. Quanto ao sexo, foi maior no feminino (59%) pelo critério do NCEP ATPIII. A insuficiência coronariana (ICo) apresentou maior freqüência entre os pacientes com SM ( 24,8% NCEP ATPIII e 24,3% IDF, p<0,001), relação não observada com os portadores de acidente vascular cerebral (AVC). Após análise ajustada dos fatores de risco pela IDF, idade > 40 anos e índice de massa corporal (IMC) > 30kg/m2 foram as variáveis mais associadas à maior risco de SM ( p<0,001). A concordância geral entre os dois critérios foi de 0,70 ( p<0,001), sendo maior no sexo feminino, 0,82 do que no masculino, 0,58. Concluiu-se que, em ambulatórios de cardiologia, a prevalência da SM é bem mais elevada que a população geral, foi mais prevalente no sexo feminino pelo NCEP ATPIII e esteve mais associada com ICo. Houve uma boa concordância entre os métodos utilizados para avaliá-la, sendo ótima para o sexo feminino, mas, regular para o masculino, sugerindo que os critérios atualmente utilizados não estão adequados para o diagnóstico da SM no sexo masculino. Possivelmente o ponto de corte da cintura usado na IDF, foi o maior responsável pela baixa concordância encontrada entre as duas definições no sexo feminino.

Made available in DSpace on 2016-08-19T18:16:03Z (GMT). No. of bitstreams: 1 DISSERTACAO AIZA LEAL.pdf: 4046960 bytes, checksum: 7d3ca05d04d267fdbb4345764aeea25f (MD5) Previous issue date: 2011-12-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Studies have been conducted to determine the association between metabolic syndrome and coronary artery disease. The current perspective is to investigate whether there are gender differences in his presentation to determine significant changes in prevention and treatment. In this context, this study aimed to evaluate the association of metabolic syndrome with coronary artery disease and verify the gender difference in their characteristics. We evaluated 325 patients who consecutively underwent coronary angiography for investigation of coronary artery disease. Metabolic syndrome was defined according to criteria of National Cholesterol Education Program's Adult Treatment Panel III. It was considered as coronary artery disease the presence of obstruction in the coronary arteries demonstrated by angiography. To verify the association and distribution of their frequencies between the studied variables used the chi-square tests, Student's t, and nonparametric Mann-Whitney test. The levels of significance for all tests was &#945; &#8804; 0.05 and confidence interval of 95%. The prevalence of MS was 54.7% in men and 45.3% in women, with statistical significance. While coronary artery disease had a prevalence of 66.4% and 33.6% respectively for male and female, also statistically significant. The association SM and Coronary Artery Disease was elevated in both sexes, and more present in women, with statistical significance. Hypertriglyceridemia was the component of metabolic syndrome more common in both sexes in the presence of coronary artery disease, followed by low HDL cholesterol in men and high blood pressure in women, these differences were statistically significant. It is concluded that metabolic syndrome was highly prevalent in the population with CAD were no differences between the sexes, women were more affected by the association of metabolic syndrome and coronary artery disease. / Estudos têm sido realizados para determinar a associação entre Síndrome Metabólica e Doença Arterial Coronariana. A perspectiva atual é investigar se há diferença de gênero em sua apresentação que determine mudanças significativas na sua prevenção e tratamento. Neste contexto, este estudo teve como objetivo avaliar a associação da síndrome metabólica com a Doença Arterial Coronariana e verificar a diferença entre sexos nas suas características. Avaliou-se 325 pacientes submetidos consecutivamente à cineangiocoronariografia para investigação de Doença Arterial Coronariana. A Síndrome Metabólica foi caracterizada segundo os critérios do National Cholesterol Education Program's Adult Treatment Panel III. Foi considerada como Doença Arterial Coronariana a presença de obstrução em artérias coronárias demonstrada pela cineangiocoronariografia. Para verificar a associação e a distribuição de suas freqüências entre as variáveis estudadas utilizaram-se os Testes do qui-quadrado, t de Student, e o não paramétrico Mann-Whitney. Os níveis de significância para todos os testes foi de &#945; &#8804; 0.05 e intervalo de confiança de 95%. A prevalência de SM foi de 54,7% nos homens e 45,3% nas mulheres, com signifiância estatística. Enquanto que a Doença Arterial Coronariana apresentou prevalência de 66,4% e 33,6%, respectivamente para sexo masculino e feminino, também com significância estatística. A associação SM e Doença Arterial Coronariana esteve elevada em ambos os sexos, e mais presente em mulheres, havendo significância estatistica. A hipertrigliceridemia foi o componente da Síndrome Metabólica mais frequente em ambos os sexos na presença de doença arterial coronariana, seguido do HDL colesterol baixo nos homens e da elevação da pressão arterial em mulheres, estas diferenças foram significante estatisticamente. Conclui-se que síndrome metabólica mostrou-se muito prevalente na população com DAC e houve diferença entre os sexos, as mulheres foram mais acometidas pela associação da Síndrome Metabólica e Doença Arterial Coronariana.

Resumo: Doença cardiovascular (DCV) está entre as principais causas de morbimortalidade e obesidade é um de seus fatores de risco. O melhor prognóstico de pacientes obesos gerou um paradoxo e a investigação de outros indicadores de obesidade como preditores de doença arterial coronariana (DAC). A associação de razão cintura-quadril e circunferência da cintura, marcadores de obesidade central, com doença coronariana determinada angiograficamente ainda não respondeu essa questão adequadamente. Além disso, a associação com circunferência do pescoço, marcador de obesidade visceral, não foi avaliada. Nesse estudo, avaliou-se a associação de obesidade – central, visceral e geral - com gravidade e extensão da doença coronariana. Métodos e Resultados: Estudo caso-controle foi conduzido em 376 pacientes, com 40 anos ou mais, com doença coronariana crônica, submetidos à cineangiocoronariografia eletiva. Índice de Massa Corporal (IMC), circunferência cintura, razão cintura-quadril (RCQ) e circunferência do pescoço foram aferidos. Doença coronariana significativa foi definida na presença de pelo menos 50% de estenose coronariana em um dos vasos epicárdicos (casos). Controles foram selecionados entre aqueles sem doença coronariana significativa. Foram identificados 155 casos e 221 controles e calculada odds ratio e IC 95%, com e sem controle para fatores de confusão. Houve predomínio de homens entre os casos, assim como idade entre 50-59 e mais de 70 anos. Razão cintura-quadril foi o principal preditor independente de DAC, seguido de circunferência do pescoço. Razão cintura-quadril associou-se fortemente com DAC nas análises univariada (OR= 3,7; IC 95%1,4-10,1 p=0,02) e o efeito tornou-se mais evidente na multivariada (OR= 4,0 IC 95% 1,3-12,1 p=0,03). Circunferência do pescoço só tornou-se significativamente associada no modelo multivariado (OR= 2,4 IC 95% 1,1-5,3 p= 0,04), assim como a categoria de obesidade do índice de massa corporal. Conclusões: Obesidade central, determinada por RCQ, é fator de risco independente para doença coronariana significativa, assim como circunferência do pescoço. / Introduction: Cardiovascular Disease is one of the main causes of morbimortality while the obesity is one of its risk factors. The best prognosis of obese patients has led to a paradox and the investigation of other obesity indicators as the coronary artery disease predictors (CAD). The association of waist-hip ratio and waist circumference, which are markers of central obesity with angiographically determined coronary disease has not yet answered that question adequately. In addition to that, the association with neck circumference as a marker of visceral obesity has not been evaluated. In this study, we have evaluated the association of central, visceral and general obesity with severity and extent of coronary artery disease. Methods and Results: A case-control study was conducted in 376 patients, aged 40 years or more, with chronic coronary disease, undergoing the elective cineangiography. Body Mass Index (BMI), waist circumference, waist-hip ratio (WHR), and neck circumference have been measured. Significant coronary disease was defined in the presence of at least 50% of coronary stenosis in one of the epicardial vessels or their branches, with diameter greater than three mm (cases). Controls have been selected among those without significant coronary disease. At the enrolment, 155 cases and 221 controls were identified. Odds ratios and the confidence intervals of 95% (95%CI) were calculated in the crude and multivariate analysis. There was a predominance of men in the cases, as well as aged 50-59 and over 70 years. The WHR was the main independent predictor of CAD, followed by the neck circumference. The waist-hip ratio was strongly associated with CAD in univariate analysis (OR= 3.7; 95%CI 1.4-10.1; P=0.02) and the effect became more evident controlling for confounding factors (OR = 4.0 95%CI 1.3-12.1; P=0.03). The neck circumference became significantly associated with CAD in the multivariate model (OR = 2.4 95% CI 1.1-5.3; P = 0.04), as well as obesity, in the category of BMI. Conclusions: Central obesity, as determined by WHR, was an independent risk factor for significant coronary disease, as well as the neck circumference.

A ecocardiografia com perfusão miocárdica em tempo real (EPMTR) permite análise simultânea da contração segmentar miocárdica e análise qualitativa da perfusão miocárdica (PQL), além da quantificação da reserva de fluxo sanguíneo do miocárdio (FSM). A EPMTR quantitativa tem demonstrado melhorar a acurácia na detecção de doença arterial coronariana (DAC), todavia, seu valor prognóstico é desconhecido. Os objetivos deste estudo foram determinar o valor prognóstico das alterações transitórias da CSM e do FSM regional em pacientes com DAC suspeita ou confirmada e identificar dentre os parâmetros analisados qual o melhor preditor de eventos cardíacos. Estudamos 227 pacientes que se submeteram ECMTR sob estresse pela adenosina e 168 pela dobutamina, com sistema de baixo índice mecânico após infusão intravenosa de agente de contraste ecocardiográfico. A reserva de velocidade de repreenchimento () e um índice de fluxo sanguíneo do miocárdio (Anx) foram obtidos a partir da EPMTR quantitativa utilizando-se software Q-Lab. Reserva e reserva do FSM (Ax) foram determinadas como a razão entre os valores obtidos durante o estresse pela adenosina/dobutamina e o repouso. Eventos foram determinados como morte cardíaca, infarto do miocárdio não-fatal, angina instável (eventos maiores) e revascularização do miocárdio percutânea ou cirúrgica (eventos menores). Durante uma média de acompanhamento de 32 meses - adenosina e 34 meses - dobutamina (5 dias - 6,9 anos), 46 eventos ocorreram no grupo adenosina (2 mortes, 6 infartos do miocárdio não-fatais e 11 angina instável) e 38 eventos no grupo dobutamina (3 mortes, 3 infartos do miocárdio não-fatais e 11 angina instável). Pela curva Receiver Operator Characteristics (ROC). os valores de corte da reserva utilizados foram de 2,1 e 2,45 e da reserva de FSM foram de 2,26 e 2,78, para adenosina e dobutamina, respectivamente. A CSM e a PQL foram preditores independentes de eventos totais, pela EPMTR sob estresse pela adenosina (RR,2,8; IC95%; p=0,003 e RR,4,3; IC95%; p<0,001, respectivamente), mas não para eventos maiores. Todavia, foram preditores independentes de eventos totais (RR,3,3; IC95%; p=0,002 e RR,6,7; IC95%; p<0,001, respectivamente) e maiores (RR,3,3; IC95%; p=0,024 e RR,3,7; IC95%; p=0,018, respectivamente) para EPMTR sob estresse pela dobutamina. Os parâmetros quantitativos, reserva e reserva Ax adicionaram valor prognóstico sobre as demais variáveis durante EPMTR pela adenosina para eventos totais (RR,16,5; IC95%, p<0,001 e RR,7,9; IC95%; p<0,001, respectivamente), sendo os únicos preditores de eventos maiores neste grupo (RR,8,7; IC95%; p=0,005 e RR,5,9; IC95%; p=0,023) quando anormais em 2 ou mais territórios coronarianos. Estes parâmetros adicionaram valor prognóstico sobre as demais variáveis durante EPMTR pela dobutamina (RR,23,7; IC95%; p<0,001 e RR,16; IC95%; p<0,001,respectivamente), todavia, somente a reserva , mas não a Ax, foi preditor de eventos maiores neste grupo (RR,21; IC95%; p=0,003) quando anormal em 2 ou mais territórios coronarianos. Concluimos que os parâmetros quantitativos do fluxo sanguíneo miocárdio obtidos pela EPMTR sob estresse pela adenosina e dobutamina fornecem informação prognóstica independente e adicional sobre a análise da CSM e análise qualitativa da perfusão miocárdica em pacientes com suspeita de DAC. Os parâmetros quantitativos, em particular a reserva pode prever pacientes com ainda pior prognóstico (os pacientes com reservas anormais em dois ou mais territórios coronarianos) / Real-time myocardial contrast echocardiography (RTMCE) permits simultaneous analysis of wall motion (WM) and qualitative myocardial perfusion (QMP) beyond quantification of myocardial blood flow reserve (MBFR). Although quantitative RTMCE has been demonstrated to improve the accuracy for detecting coronary artery disease (CAD), its prognostic value is unknown. We sought to determine the prognostic value of transient changes in myocardial WM, QMP and myocardial blood flow during adenosine and dobutamine stress RTMCE in patients with known or suspected CAD and to identify among the parameters, the best predictor of outcome. We studied 227 patients who underwent adenosine stress RTMCE and 168 patients who underwent dobutamine stress RTMCE with low-mechanical index pulse sequence schemes following intravenous infusion of contrast agent. The replenishment velocity reserve () and an index of myocardial blood flow (Anx) were derived from quantitative RTMCE using Q-Lab software. reserve and MBFR reserve was determined as the ratio of values obtained during adenosine/dobutamine and baseline. The study end points were primary outcomes which included: cardiac death, myocardial infarction and unstable angina; and secondary outcomes: which included coronary bypass or angioplasty. During a median follow-up of 32 months - adenosine and 34 months-dobutamine (5 days-6,9years), 46 events occurred adenosine (2 death, 6 nonfatal myocardial infarctions and 11 unstable angina) and 38 events ocurred-dobutamine (3 death, 3 nonfatal myocardial infarctions and 11 unstable angina). By receiver operator characteristics curve, the cut-off value of were 2.1 and 2.45 and of MBRF were 2.26 and 2.78, for adenosine and dobutamine respectively. WM and QMP analysis were independent predictors of total events by adenosine stress RTMCE (RR,2.8,95%,p=0.003 and RR4.3,95%,p<0.001, respectively) but not for primary events. However, were independent predictors of total events (RR,3.3,95%, p=0.002 and RR6.7,95%, p<.001, respectively) and primary events (RR3.3,95%, p=0.024 and RR3.7,95%, p=0.018, respectively) for dobutamine stress RTMCE. Quantitative parameters, both and Ax reserves added even more prognostic value over other variables during adenosine stress RTMCE for total events (RR,16.5,95%, p<0.001 and RR7.9, 95%, p<0.001, respectively), and these parameters were the only predictors of primary events in this group (RR,8.7,95%,p=0.005 and RR5.9,95%, p=0.023) when this parameters were abnormal in two or more coronary territories. These parameters added even more prognostic value over other variables during dobutamine stress RTMCE (RR,23.7,95%, p<0.001 and RR,16,95%,p<0.001, respectively), however, only reserve but not Ax reserve was good and independent predictor of primary events in this group (RR,21,95%,p=0.003) when this parameter was abnormal in two or more coronary territories . In conclusion, the quantitative parameters obtained from adenosine and dobutamine stress Real Time Myocardial Contrast Echocardiography have independent and additional prognostic information over wall motion analysis and qualitative myocardial perfusion in patients with suspected or known coronary artery disease. And, the quantitative analysis of myocardial perfusion, in particular with the B parameter, identifies a subgroup with greater risk for cardiovascular events (those patients with abnormal reserves in two or more coronary territories)

Red blood cells (RBC) have been shown to mediate plaque development seen in coronary artery disease (CAD). This study determined whether differences in RBC fatty acid (FA) composition were related to CAD risk. FAs were extracted from RBCs of 38 individuals who have undergone cardiac catheterization, 9 of whom had obstructive CAD, and analyzed via gas chromatography. Ferric reducing ability of plasma (FRAP) assay was used to determine oxidative stress. Food frequency questionnaires were used to correlate RBC omega-3 FA to daily intake of omega-3 FA. No correlation was found between RBC content and intake of omega-3 FA. FRAP values and RBC FA composition did not differ between the 2 groups with exception of the saturated FA, palmitic acid (p=0.018). These results suggest that RBC FA composition may differ between individuals with or at risk for CAD. Additional research is needed to validate this biomarker as a predictor of CAD.

INTRODUCTION: The risk factors for cardiovascular disease (CVD) are associated with coronary atherosclerosis and having multiple risk factors potentiates atherosclerosis. This study examined the prevalence of multiple biological and lifestyle/behavioral risk factors and their association with coronary artery calcium (CAC), a marker for subclinical coronary atherosclerosis. METHODS: This is a cross-sectional study of 1607 community-dwelling asymptomatic individuals from central Appalachia who participated in CAC screening between January 2011 and December 2012. Data on demographics (sex and age) and 7 traditional risk factors for coronary artery disease (CAD) were collected and categorized into 5 groups (0-1, 2, 3, 4, and ≥5). Prevalence of these risk factors and CAC scores (0, 1-99, 100-399, ≥400) were assessed, and the impact of the number of risk factors on CAC scores were delineated using multiple logistic regression. RESULTS: Over 98% of participants had ≥1 risk factor. While obesity, diabetes, hypertension, and family history of CAD significantly increased the odds of having CAC, CAC scores significantly increased with number of risk factors. After adjusting for demographic factors, having 3, 4, and ≥5 risk factors was significantly associated with increased odds of having higher CAC scores when compared to zero CAC score by more than one and half times [OR=1.65, CI (1.20-2.25)], two times [OR=2.32, CI (1.67-3.23)] and three times [OR=3.45, CI (2.42-4.92)], respectively. CONCLUSION: The high prevalence of multiple risk factors in the study population suggests the need for aggressive multiple risk factors interventions for primary prevention of CAD, which could address CVD health disparities.

Aim: To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes. Methods: : A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted. Results: : In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively. Conclusion: : There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.