Cerebral ischemia leading to an ischemic stroke is a possible complication of a transcatheter aortic valve replacement (TAVR) procedure. This is because embolic debris can become dislodged and travel through the aortic arch, where they either continue to the descending aorta and join the systemic circulation or travel into the cerebral vasculature through the three daughter vessels that branch off the top of the aortic arch. These three vessels are the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. These three vessels lead either directly or indirectly to the cerebral vasculature, where the diameter of vessels become very small. If a large enough embolus travels into the cerebral vasculature, it can become stuck in the small cerebral vessels, blocking blood flow and cutting off the supply of oxygen to brain cells. The purpose of this study is to expand upon previous work in order to 1) create a more accurate physics simulation of blood and debris flow through the aortic arch 2) report on embolic debris distribution through the aortic arch and 3) analysis on which physical parameters affect embolic debris distribution. The physical parameters analyzed were particle diameter and particle density. This study was performed by creating a finite element model in COMSOL Multiphysics™ using a SolidWorks model of an aortic arch, with dimensions taken from a patient’s CT scan. Computational fluid dynamics was performed using a pulsatile pressure waveform throughout the aortic arch with a non-constant viscosity model. Once the velocity profile through the aortic arch matched with value ranges from literature, the particle tracing study was implemented. Both a pulsatile pressure waveform and a constant pressure model were analyzed, as well as a constant viscosity model and a non-constant viscosity model. The pulsatile pressure waveform influenced particle distribution and is recommended for future studies since this model leads to pulsatile flow, which is representative of flow through the aorta. It was seen that the non-constant viscosity model did not have a large effect on the velocity profile, but more than doubled the surface average value of viscosity. It also had an effect on the particle distribution through the aortic arch. Small diameter emboli were more likely to flow into the descending aorta, the brachiocephalic artery, and the left subclavian artery; larger emboli were more likely to flow into the left common carotid. Lower density emboli were more likely to flow into the descending aorta and the brachiocephalic artery. Averaging all densities and sizes, it was determined 44.8% of emboli flow into the three daughter vessels, but ultimately only 30.61% of emboli flow into the cerebral vasculature and have the potential to cause an ischemic stroke.

Ultraljudsundersökningar av arteria carotis communis (CCA) utförs med ultraljud vid bedömning av kärlförändringar och flödeshastigheter (FH) samt utredning av sjukdomar i CCA. Lumendiameter (LD) i CCA är en markör för riskfaktorer som leder till stroke, hjärtinfarkt och ateroskleros. Syftet med den aktuella studien är att studera om det sker någon vasoaktiv förändring i CCA vid konsumtion av koffein hos unga vuxna. Det var 33 försökspersoner som delades upp i grupper beroende på deras koffeinkonsumtionsvanor och undersöktes med ultraljud. Försökspersonerna hade innan undersökning inte konsumerat koffein på 12 timmar. Undersökningen utfördes innan konsumtion av koffeindryck och 45 minuter efter koffeinkonsumtion. En signifikant skillnad efter konsumtion av koffein påvisades i lågkonsument gruppen (grupp 1) (p.0,06) och högkonsument gruppen (grupp 3) (p=0,05). En positiv korrelation mellan LD innan och efter konsumtion (r=0,955; p <0,01) samt FH innan och efter konsumtion (r=0,393; p <0,01) av koffein kunde påvisas. Nyckelord: Carotisduplex, Kaffe, Vasoaktiv, CCA.

La rigidité artérielle est un facteur de risque pour les maladies cardiovasculaires et neurodégénératives, telles que la maladie d'Alzheimer. Des recherches antérieures utilisant un modèle murin de calcification de l'artère carotide ont révélé que cette rigidité entraîne des altérations structurelles, notamment la rupture des fibres élastiques, une augmentation du dépôt de collagène, un épaississement de l'intima-média, ainsi qu'une diminution de la compliance et de la distensibilité artérielles. Ces modifications contribuent à une augmentation de la pulsatilité sanguine et au stress oxydatif cérébral, ce qui entraîne une activation microgliale et astrocytaire, conduisant à une neurodégénérescence, en particulier dans l'hippocampe. Ce mémoire vise à explorer l’hypothèse selon laquelle le sildénafil, connu sous le nom de Viagra, pourrait protéger le cerveau des effets de la rigidité des artères carotides sans modifier directement cette rigidité. Contrairement aux études précédentes centrées sur les altérations cérébrales, cette étude se concentre sur les effets vasculaires du sildénafil. Les résultats montrent que le sildénafil améliore partiellement la compliance et la distensibilité des carotides, et réduit significativement les dépôts de sels calciques dans les artères, comme confirmé par des analyses histologiques et spectrophotométriques. Ces résultats enrichissent les connaissances sur les effets vasoprotecteurs du sildénafil, suggérant un potentiel thérapeutique au-delà de son usage traditionnel, pour atténuer les conséquences néfastes de la rigidité artérielle. En préservant les propriétés vasculaires sans affecter directement la fonction cérébrale, le sildénafil pourrait être considéré comme une nouvelle approche pour la gestion des risques cardiovasculaires et neurodégénératifs associés à la rigidité artérielle. / Arterial stiffness is a risk factor for cardiovascular and neurodegenerative diseases, such as Alzheimer's disease. Previous research using a murine model of carotid artery calcification revealed that this stiffness leads to structural alterations, including the rupture of elastic fibers, increased collagen deposition, thickening of the intima-media, as well as reduced arterial compliance and distensibility. These changes contribute to increased blood pulsatility and cerebral oxidative stress, which leads to microglial and astrocytic activation, resulting in neurodegeneration, particularly in the hippocampus. This thesis aims to explore the hypothesis that sildenafil, known as Viagra, could protect the brain from the effects of carotid artery stiffness without directly modifying this stiffness. Unlike previous studies focused on cerebral alterations, this study concentrates on the vascular effects of sildenafil. The results show that sildenafil partially improves the compliance and distensibility of the carotid arteries and significantly reduces calcium salt deposits in the arteries, as confirmed by histological and spectrophotometric analyses. These findings enhance the understanding of the vasoprotective effects of sildenafil, suggesting therapeutic potential beyond its traditional use, to mitigate the harmful consequences of arterial stiffness. By preserving vascular properties without directly affecting brain function, sildenafil could be considered a novel approach for managing cardiovascular and neurodegenerative risks associated with arterial stiffness.

Cardiovascular diseases are the leading causes of death worldwide and improved diagnostic methods are needed for early intervention and to select the most suitable treatment for patients. Currently, carotid artery plaque vulnerability is typically determined by visually assessing ultrasound B-mode images, which is influenced by user-subjectivity. Since plaque vulnerability is correlated to the mechanical properties of the plaque, quantitative techniques are needed to estimate plaque stiffness as a surrogate for plaque vulnerability, which would reduce subjectivity during plaque assessment. The work in this thesis focused on three noninvasive ultrasound-based techniques to quantitatively assess plaque vulnerability and measure arterial stiffness. In Study I, a speckle tracking algorithm was validated in vitro to assess strain in common carotid artery (CCA) phantom plaques and thereafter applied in vivo to carotid atherosclerotic plaques where the strain results were compared to visual assessments by experienced physicians. In Study II, hard and soft CCA phantom plaques were characterized with shear wave elastography (SWE) by using phase and group velocity analysis while being hydrostatically pressurized followed by validating the results with mechanical tensile testing. In Study III, feasibility of assessing the stiffness of simulated plaques and the arterial wall with SWE was demonstrated in an ex vivo setup in small porcine aortas used as a human CCA model. In Study IV, SWE and pulse wave imaging (PWI) were compared when characterizing homogeneous CCA soft phantom plaques. The techniques developed in this thesis have demonstrated potential to characterize carotid artery plaques. The results show that the techniques have the ability to noninvasively evaluate the mechanical properties of carotid artery plaques, provide additional data when visually assessing B-mode images, and potentially provide improved diagnoses for patients suffering from cerebrovascular diseases. / <p>Doctoral thesis in medical technology and medical sciences</p><p>QC 20160921</p>

La rigidité artérielle est considérée comme un facteur de risque important pour le développement du déclin cognitif. Toutefois, les effets précis de la rigidité artérielle sur le cerveau sont peu connus et, à ce jour, aucun modèle animal ne permet d’étudier l’effet isolé de ce facteur sur l’homéostasie cérébrale. Dans cette étude, nous avons développé un nouveau modèle de rigidité artérielle qui se base sur la calcification de l’artère carotide chez la souris. Au niveau artériel, ce modèle présente une fragmentation de l’élastine, une augmentation de la distribution du collagène et de l’épaisseur intima-média ainsi qu’une diminution de la compliance et de la distensibilité artérielles démontrant la rigidité artérielle. De plus, le modèle ne présente pas d’augmentation de pression artérielle ni de changement de rayon du lumen indiquant une absence d’hypoperfusion globale et d’anévrisme. Au niveau cérébral, les résultats montrent que la rigidité artérielle induit une augmentation de la pulsatilité du flux sanguin cérébral menant ainsi à une augmentation du stress oxydatif. Ce dernier induit une inflammation cérébrale, détectée par l’activation de la microglie et des astrocytes, induisant ultimement une neurodégénérescence. Ces effets sont surtout observés au niveau de l’hippocampe, la région cruciale pour la mémoire et la cognition. Ainsi, cette étude montre que la rigidité artérielle altère l’homéostasie cérébrale et mérite d’être considérée comme une cible potentielle dans la prévention et le traitement des dysfonctions cognitives chez les personnes âgées. / Arterial stiffness is considered as an important risk factor for the development of cognitive decline in the elderly population. However, its precise effects on the brain are unknown and, to date, no animal model allows to study the precise outcome of arterial stiffness on the brain homeostasis. In this study, we developed a new animal model of arterial stiffness based on the calcification of the carotid artery in mice. On the arterial level, this model shows a fragmentation of elastin, increased collagen distribution and intima-media thickness as well as decreased arterial compliance and distensibility, thus fulfilling the major arterial stiffness properties. In addition, this model does not a show an increase in blood pressure or change in arterial lumen radius indicating a lack of global hypoperfusion and aneurysm. Regarding the brain, the results show that arterial stiffness induces an increase in cerebral blood flow pulsatility leading to increased oxidative stress. Oxidative stress induces brain inflammation, detected by the activation of microglia and astrocytes, ultimately leading to neurodegeneration. These effects are particularly observed in the hippocampus, a crucial area for memory and cognition. Thus, this study shows that arterial stiffness alters brain homeostasis and therefore should be considered as a potential therapeutical target for the prevention and treatment of cognitive dysfunction in the elderly.

Made available in DSpace on 2016-03-22T17:26:32Z (GMT). No. of bitstreams: 1 MESTRADO FERNANDA.pdf: 502799 bytes, checksum: ac66c75ef6d7608e98e8cb58e8b514d8 (MD5) Previous issue date: 2010-12-09 / OBJECTIVES: Assess the carotid intima-media thickness (IMT) in a sample of male adolescents in a southern Brazil city, and investigate the association of this measure with biological and demographics variables. METHODS: Cross-sectional study in a random sample of 239 eighteen years old male adolescents, in the Pelotas city military recruitment, in the south of Brazil, held in July 2010. The presence of cardiovascular risk factors was investigated by a questionnaire and physical examination (weight, height, blood pressure and waist circumference). The study was performed in B-mode ultrasound of both common carotid arteries, with IMT measurement in the posterior wall, at a distance of 1.0 to 2.0 cm of the carotid bifurcation. We obtained five measurements of each common carotid and the mean of both sides corresponded to the carotid IMT of each participant. RESULTS: The mean carotid IMT was 0.4969 (± 0.0466) mm and atheromatous plaque were not identified in any adolescent. In the multivariate analysis, BMI (p=0.005) and waist circumference (p<0.001) were positively associated with carotid IMT. CONCLUSION: The association of BMI and waist circumference with the carotid IMT during adolescence shows the importance of adiposity as a cardiovascular risk factor / OBJECTIVES: Assess the carotid intima-media thickness (IMT) in a sample of male adolescents in a southern Brazil city, and investigate the association of this measure with biological and demographics variables. METHODS: Cross-sectional study in a random sample of 239 eighteen years old male adolescents, in the Pelotas city military recruitment, in the south of Brazil, held in July 2010. The presence of cardiovascular risk factors was investigated by a questionnaire and physical examination (weight, height, blood pressure and waist circumference). The study was performed in B-mode ultrasound of both common carotid arteries, with IMT measurement in the posterior wall, at a distance of 1.0 to 2.0 cm of the carotid bifurcation. We obtained five measurements of each common carotid and the mean of both sides corresponded to the carotid IMT of each participant. RESULTS: The mean carotid IMT was 0.4969 (± 0.0466) mm and atheromatous plaque were not identified in any adolescent. In the multivariate analysis, BMI (p=0.005) and waist circumference (p<0.001) were positively associated with carotid IMT. CONCLUSION: The association of BMI and waist circumference with the carotid IMT during adolescence shows the importance of adiposity as a cardiovascular risk factor

O acidente vascular cerebral (AVC) e a primeira causa de obito no Brasil e a principal de incapacidade no mundo. A doenca aterosclerotica carotidea esta associada a cerca de 15% dos AVC. A endarterectomia cirurgica e o tratamento padrao-­ouro para as estenoses carotideas sintomaticas. A angioplastia carotidea com stent via endovascular (ACS) e uma alternativa terapeutica a endarterectomia. O desenvolvimento de dispositivos de protecao embolica levou a reducao das taxas de complicacao durante a ACS. A tecnica de protecao mais utilizada na pratica clinica e a protecao distal com filtro. As estrategias de protecao proximal, por bloqueio ou reversao do fluxo carotideo, tem revelado resultados promissores em relacao a protecao distal com filtro durante a ACS. Assim, o objetivo do estudo foi comparar a reversao de fluxo e o filtro de protecao durante a ACS. Os objetivos primarios foram a incidencia, o numero e o tamanho das lesoes cerebrais isquemicas por ressonancia magnetica pela sequencia diffusion-­weighted-­imaging (DWI) apos a ACS. Os objetivos secundarios foram as complicacoes cardiacas e eventos cerebrovasculares (CCEC), ataque isquemico transitorio (AIT) e as lesoes cerebrais isquemicas definitivas na imagem por ressonancia magnetica pela sequencia fluid-­attenuated inversion recovery (FLAIR) no seguimento de tres meses. As lesoes isquemicas foram obtidas por ressonancia magnetica (RM) de campo 3 Tesla. Os pacientes foram avaliados quanto aos desfechos neurologicos atraves das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS). Quarenta pacientes foram incluidos randomicamente no estudo. Comparado a reversao de fluxo (n=21) o filtro de protecao (n=19) resultou em uma reducao significativa na incidencia (15,8% vs. 47,6%, p=0,03), no numero (0,73 vs. 2,6, p=0,05) e no tamanho (0,81 vs. 2,23 mm, p=0,05) das novas lesoes cerebrais isquemicas. Dois pacientes, um de cada grupo, apresentaram AIT no seguimento de tres meses. Nao foram observadas CCEC na internacao ou no seguimento de tres meses. Neste estudo, o filtro de protecao mais eficaz que a reversao de fluxo na protecao cerebral durante a angioplastia carotidea com stent por acesso femoral. / Objectives: Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow-­reversal versus filter protection during CAS through femoral access. Methods: Patients were randomly enrolled in CAS using flow-­reversal or filter protection. The primary endpoints were the incidence, number and size of new ischemic brain lesions after CAS. The secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE), transient ischemic attack (TIA) and definitive ischemic brain lesions on fluid-­attenuated inversion recovery magnetic resonance image (FLAIR-­MRI) at a three-­month follow-­up. Ischemic brain lesions were assessed by a 3T-­MRI. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Results: Forty consecutive patients were randomly assigned. Compared to flow-­reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% vs. 47.6%, p=0.03), number (0.73 vs. 2.6, p=0.05) and size (0.81 vs. 2.23 mm, p=0.05) of new ischemic brain lesions. Two patients, one from each group, presented TIA at the three-­month follow-­up. There were no MACCE in the hospital or at the three-­month follow-­up. Conclusions: In this small sample size trial, filter protection was more effective than flow-­reversal in reducing ischemic brain lesions during CAS through femoral approach.

Introdução: O Stent Carotídeo (SC) surgiu como uma alternativa à cirurgia de endarterectomia para o tratamento de estenose carotídea extracraniana com o objetivo de prevenir o acidente vascular encefálico (AVE). O sucesso do SC depende de estratégias que minimizem o risco de AVE. No início do estudo não existiam estudos randomizados comparando o implante de stent carotídeo com diferentes tipos de proteção cerebral. Objetivos: Testar de forma aleatória a eficácia de dois diferentes princípios de proteção embólica no território carotídeo (Angioguard®) e Mo.Ma), utilizando a ressonância magnética ponderada em Difusão (RM-PD) para detectar novas lesões isquêmicas no encéfalo analisando número, tamanho e localização. Métodos: Sessenta pacientes submetidos ao implante do stent carotídeo (SC), foram alocados aleatoriamente para utilizar filtro distal Angioguard® (30 pacientes) e balão de oclusão proximal Mo.Ma (30 pacientes) desde julho de 2008 a 2011. Todos os pacientes realizaram RM-PD pré e 48 horas pós o SC. Os resultados foram avaliados por neurologista independente e cego ao tipo de proteção cerebral utilizada. Foram acompanhados por um período de pelo menos um ano. Os dados qualitativos foram resumidos em frequências absolutas e relativas (porcentagens) e comparados utilizando o teste quiquadrado com correção de continuidade de Yates ou o teste exato de Fisher. Os dados quantitativos foram expressos em médias e desvio-padrão, e/ou medianas e intervalos interquartis e foram comparadas utilizando o teste t de Student ou não paramétrico de Mann-Whitney. Resultados: Não houve diferença estatisticamente significativa em quanto a antecedentes clínicos ou características das lesões carotídeas entre os grupos, apenas as lesões eram mais calcificadas no grupo Angioguard® (p < 0,01). Não houve diferença entre os grupos quanto a incidência de novas lesões isquêmicas (63,3% do Angioguard® vs 66,7% do Mo.Ma, p = 0,787). Quando presentes, as lesões isquêmicas por pacientes o fizeram em número significativamente menor no grupo Mo.Ma, entre 1 e 43 lesões (mediana = 6), comparado ao grupo AngioguardÒ, entre 1 e 76 lesões (mediana = 10) com p < 0,001. Três pacientes (5%) apresentaram eventos neurológicos em até 30 dias e no seguimento de um ano, 1 paciente teve um infarto agudo do miocárdio. Conclusão: Foram observadas novas lesões isquêmicas cerebrais em mais de 60% dos pacientes que utilizaram os dois dispositivos de proteção cerebral, entretanto houve significativamente menos lesões por paciente no grupo Mo.Ma, com significância estatística p = < 0,001. A maioria das lesões foi pequena < 0,5 mm, e encontradas em território ipsilateral. Não foi observado óbito ou AVE maior no seguimento de pelo menos um ano. / Background: Carotid Stent (CAS) has emerged as an alternative to surgical carotid endarterectomy for the treatment of extracranial carotid stenosis in order to prevent stroke. The success of the CAS depends on estrategies that minimize the risk of stroke. When this study began there were no randomized trial comparing different types of cerebral protection during carotid stenting. Objectives: Randomly test the effectiveness of two different embolic protection principles in carotid artery (Angioguard®) vs Mo.Ma) using diffusion-weighted magnetic resonance imaging (DWI) to detect new ischemic lesions in the brain, analyzing the number, size and location of this new ischemic lesions between groups. Methods: Sixty patients undergoing CAS, were randomly assigned to use distal filter AngioguardÒ (30p) and proximal balloon occlusion Mo.Ma (30p) from July 2008 to July 2011. All patients underwent DWI before and 48 hours after the CAS. The results were evaluated by an independent neuroradiologist blind to the type of cerebral protection used. The patients were followed during at least year. Qualitative data were summarized as absolute and relative frequencies (percentages) and compared using chisquare test with Yates continuity correction or Fisher\'s exact test. Quantitative data were expressed as means and standard deviations, and / or medians and interquartile ranges and were compared using the Student t test or nonparametric Mann-Whitney test. Results: Demographic, clinical and lesion characteristics were not different between the two groups, there were more calcified lesion in the Angioguard® group (p < 0.001). There was no difference between groups regarding the incidence of new ischemic lesions in the Angioguard® group compared to the Mo.Ma group (63.3% vs 66.7% p = 0.787). When present, the number of ischemic cerebral lesions per pacient were in fewer number in the Mo.Ma group (1 to 43 lesions; median = 6) compared to the Angioguard® group (1 to 76 lesions; median = 10) p < 0.001 and this difference was significant. Three patients (5%) had neurological events within 30 days with complete regression of symptoms, and one patient develop an infarction during the first year of follow-up. Conclusions: There were new cerebral ischemic lesions detected by DWI in more than 60% of the patients in both groups, on the other hand there were significantly fewer lesions per patient in those allocated to Mo.Ma as compared to Angioguard® with statistical significance p = 0.001. Most lesions were small < 0.5mm, and localized in ipsilateral territory. There was no death or disabling stroke in at least one year of follow-up.

A hipercolesterolemia familiar (HF) é uma doença autossômica dominante caracterizada por níveis elevados de LDL-c e doença arterial coronária (DAC) precoce. Existem evidências de maior prevalência de aterosclerose subclínica nesta população avaliada pelo escore de cálcio (CAC) e pela espessura íntima-média carotídea (EIMC). O objetivo do nosso estudo foi avaliar aterosclerose subclínica por meio da angiotomografia de coronárias em portadores de HF sem aterosclerose manifesta, correlacionando os achados com parâmetros clínicos, laboratoriais, rigidez aórtica e carotídea e com a EIMC. Incluímos 102 HFs, (45±13 anos, 36% homens, LDL-c 280±54mg/dL) e 35 controles (46±12 anos, 40% homens, LDL-c 103±18mg/dL). O grupo HF apresentava maior carga de placa aterosclerótica representado por: maior número de pacientes com placa (48% versus 14%, p=0,0005), maior número de pacientes com estenose luminal acima de 50% (19% versus 3%, p=0,015), maior número total de segmentos com placas (2,0±2,8 versus 0,4±1,3, p=0,0016), maior número de segmentos com placas calcificadas (0,8±1,54 versus 0,11±0,67, p= 0,0044) e maior escore de cálcio pelo método de Agatston (55±129, mediana:0 versus 38±140, mediana:0; p=0,0028). Houve correlação positiva no grupo HF do número total de segmentos com placa com: idade (r=0,41, p<0,0001), escore de risco de Framingham (r=0,25, p=0,012), colesterol total (r=0,36, p<0,0002), LDL-c (r=0,27, p=0,005), HDL-c (r=0,24, p=0,017), apolipoproteína B (r=0,3, p=0,0032) e escore de cálcio (r=0,93, p<0,0001). Além disso, houve correlação negativa com: variação sísto-diastólica carotídea (r=-0,23, p=0,028) e percentual de distensão carotídeo (r=-0,24, p=0,014). A análise multivariada de determinantes da presença de placa aterosclerótica, revelou que idade (OR=1,105, IC95%: 1,049-1,164, p<0,001) e colesterol total (OR=1,013, IC95%:1,001-1,025) foram as variáveis associadas com a presença da mesma. A única variável associada com presença de obstrução luminal acima de 50% foi o escore de cálcio coronário (OR=1,004; IC95%:1,001-1,008; p=0,014). Em relação a determinantes da composição de placa, na análise multivariada a presença de placa não calcificada esteve associada com o sexo masculino (OR:15,45; IC95%: 1,72-138,23, p=0,014), a placa mista com antecedente familiar de DAC precoce (OR=4,90; IC95%:1,32-18,21, p=0,018) e placa calcificada a menor chance com o sexo masculino (OR=0,21; IC95%: 0,05-0,84, p=0,027). Conclusões: Os pacientes portadores de HF apresentam maior carga de placa avaliada pela angiotomografia em comparação aos controles; idade e colesterol total associaram-se a presença de placas no grupo HF; o escore de cálcio associou-se a presença de estenose luminal acima de 50%. / Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by high LDL-c levels and premature coronary artery disease (CAD) onset. There is evidence of greater prevalence of subclinical atherosclerosis in this population evaluated by coronary calcium score (CCS) and carotid intima-media thickness (IMT). The aim of our study was to assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) in patients with FH without manifest atherosclerosis and correlate the findings with clinical and laboratory parameters, aortic and carotid stiffness and IMT. We included 102 FHs (45 ± 13 years, 36% men, LDL-c 280 ± 54mg/dL) and 35 controls (46 ± 12 years, 40% men, LDL-c 103 ± 18mg/dL). The FH group had a greater atherosclerosis plaque burden represented by: higher number of patients with coronary plaque (48% versus 14%, p = 0.0005) and with luminal stenosis greater than 50% (19% versus 3% p = 0.015), higher total number of segments with plaques (2.0 ± 2.8 versus 0.4 ± 1.3, p = 0.0016), higher number of segments with calcified plaques (0.8 ± 1.54 versus 0.11 ± 0.67, p = 0.0044) and higher CCS by the Agatston method (55 ± 129, median: 0 vs. 38 ± 140, median = 0, p = 0.0028). There were positive correlations of total number of segments with plaque in FH group with the following variables: age (r=0.41, p<0.0001), Framingham risk score (r =0.25, p=0.012), total cholesterol (r=0.36, p<0.0002), LDL-c (r=0.27, p=0.005), HDL-c (r=0.24, p=0.017), apolipoprotein B (r=0,3, p=0.0032) and CCS (r=0.93, p<0.0001). In addition there was a negative correlation with: carotid systo-diastolic variation (r=- 0.23, p=0.028) and percentage of carotid distension (r=- 0.24, p=0.014). After multivariate analysis, the determinants of plaque presence were age (OR=1.105, 95% CI=1.049-1.164, p<0.001) and total cholesterol (OR=1.013, 95% CI:1.001-1.025). The only variable associated with presence of luminal stenosis greater than 50% was CCS (OR = 1.004, 95% CI: 1.001-1.008, p=0.014). After multivariate analysis, the presence of non-calcified plaque was associated with male gender (OR: 15.45, 95% CI 1.72-138.23, p = 0.014), mixed plaque with family history of early CAD (OR = 4.90, 95%:1.32-18.21, p=0.018) and calcified plaque negatively with males (OR = 0.21, 95% CI: 0.05-0.84, p = 0.027). Conclusions: FH subjects have higher plaque burden assessed by CTCA compared to controls; age and total cholesterol were associated with the presence of coronary plaque in the FH subjects; CCS was associated with luminal stenosis greater than50%.

Introdução: As lesões contusas de artérias carótidas e vertebrais (LCCV) não são muito frequentes, porém podem apresentar repercussões graves. A incidência desse tipo de lesão é difícil de ser avaliada porque os doentes podem estar neurologicamente assintomáticos quando atendidos no pronto socorro ou podem apresentar sintomas que são atribuídos ao trauma de crânio ou a outras lesões associadas. Estatísticas recentes apontam uma incidência de 0,24% a 0,33% em doentes traumatizados portadores de algum sintoma neurológico. No Brasil não existem trabalhos de nosso conhecimento que tenham estudado a incidência das LCCV. Por outro lado, a real morbidade e mortalidade das LCCV não estão claramente determinadas, nem mesmo na literatura internacional. Os objetivos deste estudo foram: a) avaliar a incidência de LCCV em 100 doentes vítimas de trauma contuso submetidos à angiotomografia cervical, utilizando parâmetros obtidos da avaliação clínica inicial e das tomografias de crânio e da região cervical e b) verificar quais os critérios de indicação da angiotomografia cervical que mais se correlacionam com a presença de LCCV no serviço de trauma de hospital quaternário brasileiro. Material e Método: Durante o período de trinta meses a partir de julho de 2006, todos os doentes admitidos no Pronto-Socorro do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com trauma cervical fechado, com potencial risco de lesão dos vasos cervicais apresentando défice neurológico não justificado pela tomografia computadorizada de crânio, infarto cerebral, hematoma cervical estável, epistaxe volumosa, anisocoria/sinal de Horner, escore na escala de coma de Glasgow abaixo de 8 sem achados justificativos pela tomografia, fratura de coluna cervical, fratura de base de crânio, fratura de face (Le Forte II ou III), sinal do cinto de segurança acima da clavícula, frêmito ou sopro cervical, foram incluídos no estudo. Os doentes foram encaminhados para a angiotomografia cervical para diagnóstico das LCCV. Foram analisados também mecanismo de trauma, sexo, idade, gravidade do trauma, gravidade das LCCV, tipo de tratamento e evolução. Os doentes foram divididos em dois grupos: sem LCCV (Grupo I) e com LCCV (Grupo II). Os dados analisados são apresentados como média e desvio padrão da média e as análises estatísticas foram realizadas com os testes de Qui-Quadrado e Exato de Fisher, e o teste de Mann-Whitney. Foi usado um nível de significância de 5% (p-valor <=0,05). Resultado: Foram atendidos 2.467 doentes vítimas de trauma contuso. Em 100 doentes que apresentaram critérios para inclusão, no estudo a angiotomografia identificou 23 com LCCV, 17 do sexo masculino e 6 do sexo feminino. A idade média foi de 34,81±14,84 anos. Colisão de auto (49%) e atropelamento (24%) foram os mecanismos de trauma mais frequentes seguidos de queda de grande altura (18%), e outros mecanismos (9%). Dez doentes tiveram lesão de carótida interna, 2 doentes com lesão de carótida comum, onze doentes com lesão de vertebral. Sete doentes apresentaram lesão arterial grau I, 10 grau II, 4 grau IV e I grau V e uma fístula de carótida. Sete (30,4%) dos 23 doentes com LCCV apresentavam fratura de vértebras cervicais e 11 (47,8%) apresentavam fratura de face (LeFort II e III). Dezessete doentes foram tratados clinicamente e seis doentes foram submetidos a tratamento endovascular (um stent e cinco embolizações). Conclusão: Os critérios utilizados neste estudo permitiram o diagnóstico de LCCV em 0,93% dos casos, sendo que tais lesões ocorreram nos traumatizados mais graves, e não influenciaram a morte na população estudada / Background: Blunt trauma of the carotid and vertebral arteries (LCCV) are infrequent, but may have serious repercussions. The incidence of this type of injury is difficult to evaluate as many patients are neurologically asymptomatic when assisted in emergency rooms, or with symptoms attributed to cranium trauma or to other associated injuries. Recent statistical data show an incidence of 0.24% to 0.33% traumatized patients that carry some neurological symptom, we are not aware of any papers in Brazil that have studied the occurrence of LCCV. On the other hand, the real morbidity and mortality are not clearly determined, not even in the international literature. The objectives of the current study were: a) to evaluate the incidence of carotid and vertebral artery injuries in 100 patients with blunt trauma subjected to cervical angiography, using parameters obtained from the initial clinical evaluation and tomography of the patients and b) to verify which criteria for recommending cervical angiography are most related to the presence of LCCV in the trauma services section in a Brazilian quaternary care hospital. Method: During thirty months, starting in July 2006, all patients admitted in the emergency room of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, with blunt cervical trauma, with potential risk of injuries to cervical vessels that presented neurological deficit unexplained after cranial CT scan, cerebral infarction, stable cervical haematomas, severe epistaxis, anisocoria/sign of Horner`s syndrome, Glasgow coma scores bellow 8 that are not explained by CT scan, cervical spine fracture, basilar skull fracture, facial fracture (Le Forte II or III), seatbelt signals above the clavicle, cervical hum or bruit were included in the study. The patients were subjected to cervical angiography in order to diagnose LCCV. There were analyzed the mechanisms of injuries, gender, age, severity of LCCV, type of treatment and outcome. The patients were divided into two groups: without LCCV (Group I) and with LCCV (Group II). The data analyzed are presented as mean minus standard deviation and the statistical analyzes were done using Chi-square and Fisher`s exact tests, and the Mann-Whitney test. For date comparison, a p-value <=0,05 was considered significant. Results: 2.467 patients, victims of blunt trauma, were included in the study. In 100 patients that presented the criteria for the inclusion in the study, the angiography identified 23 with LCCV, 17 male and 6 female. The mean age was 34,81±14,84 years. Car crash (49%) and car-pedestrian accidents (24%) were the most frequent mechanisms of injury, followed by falling from altitude (18%), and other mechanisms (9%). Ten patients suffered internal carotid artery injury, 2 patients with common carotid artery injury, and eleven patients with vertebral artery injury. Seven patients presented arterial injury level I, 10 level II, 4 level IV and 1 level V and one carotid fistula. Seven (30,4%) out of the 23 patients with LCCV presented cervical vertebrae fractures and 11 (47,8%) presented facial fracture (LeFort II e III). Seventeen patients were treated clinically and six underwent endovascular treatment (one stent and five embolizations). Conclusion: The criteria used in this study have allowed the diagnosis of LCCV in 0,93% of the cases, those being such injuries that occurred in the most seriously traumatized patients, and did not lead to death in the studied population.