Histological verification of atherosclerosis due to bends and bifurcations in carotid arteries predicted by hemodynamic model / Confirmação histológica de aterosclerose devido a dobras e bifurcações das artérias carótidas previstas por modelo hemodinâmico

Tortuosity and bifurcations in carotid arteries alter the blood flow, causing atherosclerosis. Objectives:The aim of the present study is to analyze the effect of variant vascular anatomy in the cervical region on development of atherosclerosis by microanatomical examination. Methods: The effect of blood flow at anomalous bends and bifurcations was observed in right carotid arteries of a seventy year old female cadaver. Fifteen histological slides were prepared from the carotid arteries and interpreted to verify predictions of atherosclerosis. Results: The model predicts atherosclerosis at bends, bifurcations and large aperture arteries. Microanatomical examination revealed presence of atherosclerosis of varying thickness at the bends and bifurcation in the right carotid arteries, as predicted. Atherosclerosis was also detected in the straight part of the wider common carotid artery. No atherosclerosis was observed in the contralateral carotid arteries. The variant carotid vascular anatomy consisting of bends, bifurcations and wider arteries revealed that the shear stress and velocity of blood flow are reduced at these anomalous sites. Conclusions: Anatomical anomalies such as bends and branching in the carotid arteries alter the irrigation pattern and generate biomechanical forces that cause turbulent flow and reduce shear stress/blood flow velocity. Decreased shear stress and velocity causes development of atherosclerosis. Histological slides established the presence of atherosclerosis at bends and bifurcations and in wider arteries

Tortuosidade e bifurcações das artérias carótidas alteram o fluxo sanguíneo, causando aterosclerose. Objetivos: O objetivo do presente estudo foi analisar o efeito de anatomia vascular variante na região cervical sobre o desenvolvimento de aterosclerose via exame microanatômico. Métodos: O efeito do fluxo sanguíneo em dobras e bifurcações anômalas foi observado nas artérias carótidas do lado direito em um cadáver do sexo feminino de 70 anos de idade. Quinze lâminas histológicas foram preparadas a partir das artérias carótidas e interpretadas para confirmar as previsões de aterosclerose. Resultados: O modelo prevê aterosclerose em dobras, bifurcações e artérias de grande calibre. O exame microanatômico revelou a presença de aterosclerose de densidades variáveis nas dobras e bifurcação das artérias carótidas do lado direito, conforme previsto. Aterosclerose também foi detectada na parte reta da artéria carótida comum mais larga. Não foi observada aterosclerose nas artérias carótidas contralaterais. A anatomia vascular carotídea variante consistindo de dobras, bifurcações e artérias mais largas revelou que a tensão de cisalhamento (shear stress) e a velocidade do fluxo sanguíneo são reduzidos nesses pontos anômalos. Conclusões: Anomalias anatômicas tais como dobras e ramificações das artérias carótidas alteram o padrão de irrigação e geram forças biomecânicas que causam fluxo turbulento e reduzem a tensão de cisalhamento e a velocidade do fluxo. Tensão e velocidade menores causam o desenvolvimento de aterosclerose. As lâminas histológicas estabeleceram a presença de aterosclerose nas dobras e bifurcações nas artérias mais largas

Neutrophil-Lymphocyte ratio in cardiovascular disease risk assessment / Relação Neutrófilo-Linfócito na avaliação de risco de doença cardiovascular

The development of cardiovascular diseases with atherosclerotic origin is associated with a severe inflammatory process. Neutrophils and lymphocytes are cells sensitive to this type of disorder and their ratio, known as the NLR (neutrophil/lymphocyte ratio), has shown to be useful in clinical practice. The aim of this study was to assess the role of NLR in cardiovascular disease risk assessment. We carried out a literature review in the PubMed databases searching for articles published between 2001 to 2017 and found that NLR is in fact a useful marker for cardiovascular disease. Using NLR in patients at cardiovascular risk would be useful to delineate the prognosis of patients with this disease pattern

Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients / Frequência de Aterosclerose Subclínica em Brasileiros Infectados pelo HIV

Abstract Background: AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. Objectives: To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Methods: Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p < 0.05. Results: Plaques were found in 37% of the HIV group and 4% of controls (p < 0.001). Furthermore, carotid intima-media thickness was higher in the HIV group than in controls (p < 0.001). Patients with carotid plaque had higher fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than those without plaques. The presence of HIV, adjusted for age, overweight/obesity, and smoking increased by almost fivefold the risk of atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to protease inhibitors did not influence carotid intima-media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). Conclusions: HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

Resumo Fundamento: Aterosclerose e AIDS são importantes problemas de saúde pública. A maior sobrevida de indivíduos infectados pelo HIV acha-se associada com maior número de eventos cardiovasculares nessa população, mas tal associação ainda não foi completamente esclarecida. Objetivos: Identificar a frequência de aterosclerose subclínica em pacientes infectados pelo HIV em comparação a controles; analisar as associações entre aterosclerose e variáveis clínicas e laboratoriais, fatores de risco cardiovascular e escore de risco de Framingham (ERF) para doença coronariana. Métodos: Estudo prospectivo transversal caso-controle avaliando a presença de aterosclerose subclínica em 264 pacientes infectados pelo HIV e 279 controles. A avaliação clínica incluiu ultrassonografia das artérias carótidas, análise da rigidez arterial através da velocidade de onda de pulso (VOP) e augmentation index (AIx), exames laboratoriais do sangue periférico e determinação do risco cardiovascular segundo os critérios do ERF. O nível de significância adotado na análise estatística foi p < 0,05. Resultados: Placas foram identificadas em 37% do grupo infectado pelo HIV e em 4% dos controles (p < 0,001). A espessura médio-intimal carotídea foi maior no grupo HIV do que nos controles (p < 0,001). Pacientes com placa carotídea apresentaram maiores níveis de glicemia de jejum, colesterol total, colesterol da lipoproteína de baixa densidade e triglicérides do que aqueles sem placas. A presença do HIV, ajustada por idade, sobrepeso/obesidade e tabagismo aumentou em quase cinco vezes o risco de placa aterosclerótica carotídea (OR: 4,9; IC95%: 2,5-9,9; p < 0,001). Exposição aos inibidores da protease não influenciou a espessura médio-intimal carotídea, não se associou com frequência de placa carotídea e não alterou as características mecânicas do sistema arterial (VOP e AIx). Conclusões: Pacientes infectados pelo HIV apresentam maior risco de aterosclerose na associação com os clássicos fatores de risco cardiovascular. Tratamento com os inibidores da protease não promove alterações funcionais nas artérias, nem se associa com maior frequência de placas ateroscleróticas carotídeas. O ERF pode ser inadequado para essa população.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol / Padrão Lipídico Discordante e Placa Aterosclerótica Carotídea. Importância do Colesterol Remanescente

Abstract Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

Resumo Fundamento: Indivíduos com níveis de não HDL-C excedendo em 30 mg/dl aqueles de LDL-C (discordância lipídica) ou com altos níveis de colesterol remanescente poderiam ter maior risco cardiovascular residual. Objetivos: determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. Métodos: Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos < 4,0 mmol/l. Usou-se ultrassom para avaliar a presença de placa carotídea. Modelos de regressão logística múltipla foram construídos. Resultados: Este estudo incluiu 772 pacientes (idade média, 52 ± 11 anos; 66% mulheres). A prevalência de discordância lipídica foi de 34%. Sexo masculino e índice de massa corporal mostraram associação independente com padrão lipídico discordante. A prevalência de placa carotídea foi maior em indivíduos com discordância lipídica (40,2% vs. 29,2; p = 0,002). A análise multivariada mostrou associação do padrão lipídico discordante com maior probabilidade de placa carotídea (OR: 1,58; IC95%: 1,08-2,34; p = 0,02). Da mesma forma, identificou-se uma significativa associação entre colesterol remanescente calculado e placa carotídea. Conclusão: Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

Avaliação da subtração do artefato do fio-guia na análise quantitativa e tecidualcom ultrassom intracoronário e tecnologia iMAP® em pacientes com síndrome coronária aguda: subanálise do estudo iWonder / Evaluation of guidewire artifact subtraction in quantitative and tissue analysis with intracoronary ultrasound and iMAPTM technology in patients presenting with acute coronary syndrome: an iWonder study subanalysis

O ultrassom intracoronário (USIC) é o método adjunto mais utilizado na Cardiologia Intervencionista, e sua análise depende de normas para a aquisição, mensuração e interpretação das imagens. Ao associar a caracterização tecidual, o artefato causado pelo fio-guia pode hiperestimaro porcentual de núcleo necrótico em determinadas lesões, levando à classificação equivocada defibroateroma. Descrevemos os efeitos quantitativos e na análise tecidual resultantes da subtração do efeitodo artefato do fio-guia nas lesões ateroscleróticas em pacientes com síndrome coronária aguda. Métodos: Foram avaliados 21 pacientes com infarto do miocárdio pós-trombólise com USIC em escala de cinzas e com a tecnologia iMAP®, totalizando 76 lesões.Resultados: O USIC em escala de cinzas mostrou que as lesões tinham extensão média de 21,01 ± 18,03 mm e apresentavam elevada carga de placa (52,07 ± 7,56%). A análise pelo iMAP® demonstrou que, após a subtração do artefato do fio-guia, houve redução de todos os componentes teciduais (necrótico, calcífico, lipídico e fibrótico), porém de maneira mais acentuada do núcleo necrótico (diferença média de 3,59%). Além disso, após a subtração do artefato, 12,4% das lesões que inicialmente apresentavam núcleo necrótico ≥ 10% passaram a não ser mais classificadas como fibroateroma.Conclusões: A análise da placa de ateroma pela tecnologia iMAP® mostrou que o artefato do fio-guia superestimou o componente tecidual do núcleo necrótico. Essa interferência pode mudar errônea e categoricamente as características fenotípicas de lesões mais benignas e estáveis (fibróticas) para lesões potencialmente instáveis, como os fibroateromas, na relação de um em cada dez pacientes...

Intravascular ultrasound (IVUS) is the most widely used ancillary method in Interventional Cardiology, and its analysis depends on standards for acquisition, measurement and interpretation of the images. By associating tissue characterization, the artifact caused by the guidewire may overestimate the percentage of necrotic core in certain lesions, leading to misclassification of fibroatheroma. In this paper we described quantitative and tissue analysis effects resulting from subtracting the effect of guidewire artifact on atherosclerotic lesions in patients with acute coronary syndrome. Methods: Twenty-one patients with post-thrombolysis myocardial infarction were evaluated with grayscale IVUS and iMAPTM technology, totaling 76 lesions. Results: Grayscale IVUS showed that the lesions had a mean length of 21.01 ± 18.03 mm and revealed highplaque burden (52.07 ± 7.56%). The analysis by iMAPTM demonstrated that, after subtracting the guidewire artifact, there was a reduction of all tissue (necrotic, calcific, lipid and fibrotic) components, but more markedly in necrotic core (mean difference: 3.59%). In addition, after artifact subtraction 12.4% of the lesions that initially exhibited a necrotic core ≥ 10% ceased to be classified as fibroatheroma.Conclusions: An atheroma analysis by iMAPTM technology showed that the guidewire artifact over estimated the tissue component of the necrotic core. This interference may change, in an erroneous and categoric alway, the phenotypic characteristics of more stable and benign (fibrotic) lesions to potentially unstable lesions, for example, fibroatheromas, in a ratio of one out of ten patients...

Nonalcoholic Fatty Liver Disease Is Associated with the Presence and Morphology of Subclinical Coronary Atherosclerosis

PURPOSE: In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease. MATERIALS AND METHODS: We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques. RESULTS: Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis. CONCLUSION: Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis.

Composición y biomecánica de placas de ateroma carotídeas / Composition and biomechanics of carotid atheroma plaques

Introducción: la enfermedad aterosclerótica y sus complicaciones constituyen la causa más frecuente de muerte en el mundo. Un análisis de la relación entre parámetros estructurales y mecánicos de las placas de ateroma carotídea (PAC) es mandatorio a la hora de aumentar nuestros conocimientos en torno a los mecanismos que favorecerían la fatiga mecánica del material de la placa y su complicación. Objetivos: analizar la distensibilidad carotídea en sujetos sanos y con PAC según su composición estructural. Métodos: se estudiaron 100 sujetos asintomáticos con PAC (n=36) y sin PAC (n=64). Se clasificaron las PAC según la mediana de niveles de grises y mapeo por color en lipídicas (L), fibrolipídicas (FL) y fibrosas/calcificadas (FC). Se combinó ultrasonido modo-B con tonometría de aplanamiento y se cuantificó la distensibilidad a lo largo del eje longitudinal en cinco sectores a nivel de la PAC y de la arteria carótida normal. Resultados: se clasificaron 71 PAC (35 L, 16 FL y 20 FC), todas se encontraron en segmentos arteriales con menores niveles de distensibilidad comparado con las arterias sanas. Las PAC FC mostraron mayor rigidez a nivel del hombro proximal en comparación con las L y FL que se comportan de manera más homogénea en todos sus sectores. Conclusión: las PAC L y FL (consideradas de mayor riesgo) no presentaron el cambio significativo de rigidez parietal observado en las PAC FC, consideradas de menor riesgo de complicación. Estas diferencias biomecánicas relacionadas con la composición global de la PAC podrían tener una implicancia en la patogenia de la complicación de placa.

Introduction: the aterosclerotic disease and its complications are the most frequent cause of death in the world. An analysis of the relationship between structural and mechanic parameters of the carotid aterome plaque (CAP) is mandatory in the need of improving our knowledge concerning the mechanisms that would favor the mechanic fatigue of the plaque material and its complication. Objectives: analize the carotid distensibility in healthy persons and with patients with CAP according to their structural composition. Methods: 100 asymptomatic individuals were studied, with CAP (n=36) and without CAP (n=64). CAP persons were classified according to the standard levels of greys and color mapping in lipidic (L), fibrolipidic (FL) and fibrous/calcified (FC). B-mode Ultrasound with applanation tonometry were combined and the distensibility was quantified along the longitudinal axis in five sectors to the level of the CAP and in the normal carotid artery. Results: 71 CAP (35 L, 16 FL y 20 FC) were classified all in low-level distensibility arterial segments compared to healthy arteries. The FC CAP showed more rigidity in the proximal shoulder compared to the L and FL that behave more homogeneously in all their sectors. Conclusion: the L and FL CAPs (considered of major risk) did not present the parietal rigidity significant change observed in the FC CAP, considered of low complication risk. These biomechanic differences related to the global composition of the CAP could have an implication in the pathogenesis of the plaque complication.

Optimizing the Imaging Protocol for Ex Vivo Coronary Artery Wall Using High-Resolution MRI: An Experimental Study on Porcine and Human

OBJECTIVE: To optimize the MR imaging protocol for coronary arterial wall depiction in vitro and characterize the coronary atherosclerotic plaques. MATERIALS AND METHODS: MRI examination was prospectively performed in ten porcine hearts in order to optimize the MR imaging protocol. Various surface coils were used for coronary arterial wall imaging with the same parameters. Then, the image parameters were further optimized for high-resolution coronary wall imaging. The signal-noise ratio (SNR) and contrast-noise ratio (CNR) of images were measured. Finally, 8 human cadaver hearts with coronary atherosclerotic plaques were prospectively performed with MRI examination using optimized protocol in order to characterize the coronary atherosclerotic plaques. RESULTS: The SNR and CNR of MR image with temporomandibular coil were the highest of various surface coils. High-resolution and high SNR and CNR for ex vivo coronary artery wall depiction can be achieved using temporomandibular coil with 512 x 512 in matrix. Compared with histopathology, the sensitivity and specificity of MRI for identifying advanced plaques were: type IV-V (lipid, necrosis, fibrosis), 94% and 95%; type VI (hemorrhage), 100% and 98%; type VII (calcification), 91% and 100%; and type VIII (fibrosis without lipid core), 100% and 98%, respectively. CONCLUSION: Temporomandibular coil appears to be dramatically superior to eight-channel head coil and knee coil for ex vivo coronary artery wall imaging, providing higher spatial resolution and improved the SNR. Ex vivo high-resolution MRI has capability to distinguish human coronary atherosclerotic plaque compositions and accurately classify advanced plaques.