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Until recently, tests of vascular structure, function and compliance have been used predominantly for assessing the efficacy of treatment – for example, aggressive medical therapy may yield improvements in vascular structure and function with a concomitant decrease in cardiac events. However, the role of abnormal vessel function in the development of atherosclerosis, and the relationship of structural changes in peripheral vessels with coronary disease might suggest that these tests could be used as a screening test for patients with subclinical coronary disease. At present, there is insufficient evidence to support the theory that normal vascular structure and function can rule out significant coronary disease, and indeed, such an association may be confounded by the presence of risk factors that alter these test results in the absence of significant coronary artery disease (CAD). The overall hypothesis of the studies undertaken in this thesis was that utilizing contemporary technology during ultrasonic and tonometric assessment of arterial structure, function and compliance, it is possible to non-invasively characterise both early and advanced arterial dysfunction and identify patients both at risk and with cardiovascular disease. The aim of these studies was to determine whether these tests can be used to guide intervention when arterial dysfunction is diagnosed and whether they are robust enough as a follow-up tool. The thesis initially reviews arterial structure, function and compliance and their relationship to cardiovascular risk and in particular, CAD. This review provides a rationale for the studies undertaken here to resolve clinical and technical issues as well as provide an insight into the tests chosen to assess arterial function. The second chapter discusses the methodology used in these studies to assess arterial structure, function and compliance, diagnose coronary artery disease and determine cardiovascular risk. They range from stress echocardiography for the diagnosis of CAD to tests for arterial structure (carotid intima-media thickness [IMT]), endothelial function (brachial artery reactivity [BAR]), local arterial distensibility (distensibility coefficient [DC]) and systemic or total arterial compliance (TAC). In addition, several methods will be discussed for assessing local arterial elasticity with a novel imaging technique. The rationale for using tests for arterial structure, function and compliance in patients with CAD as well as cardiovascular risk is examined in chapter 3. Chapter 3 examines the use of TAC, IMT and BAR in patients undergoing dobutamine stress echocardiography (DSE) in a group of patients with and without disease. TAC was neither an independent predictor of CAD risk or patients having CAD in this study. BAR was a predictor of risk status but not of patients having CAD. Only IMT was an independent predictor of both patients at risk for CAD and those with CAD. In chapter 3 both pulse pressure and total arterial compliance were only univariate predictors of risk for CAD. Chapter 4 examines three different methods of estimating TAC, all based on the two-element Windkessel model in 320 patients with and without cardiovascular risk. The pulse-pressure method (PPM) is based on a combination of pressure, obtained using applanation tonometry of the radial artery, and an estimate of stroke volume obtained by Doppler echocardiography of the left ventricular outflow and by 2D echocardiographic dimension of the left ventricular outflow tract. The area method (AM) is an integral variation of the Windkessel equations and is based on the derived central pressure waveform. The stroke volume-pulse pressure method (SVPP) is a simple ratio of stoke volume and pulse pressure. We conclude that they correlate well and show similar differences between groups with and without risk. The PPM had the smallest difference from the mean and standard deviation in Bland Altman analysis and we therefore used the PPM for most future studies. Chapter 5 discusses the use of tissue Doppler for the derivation of central pressure and determination of distensibility coefficient, a marker of local arterial elasticity. Tissue Doppler can be used to evaluate the low frequency, high amplitude signals which come from tissue by changing filtering settings on an ultrasound machine. Using off-line software, the tissue velocities can be extracted and with a processing algorithm, vessel wall displacement values over time can be generated. These vessel wall displacement values which are in microns (µm) can then be used to calculated distensibility coefficient which is calculated as 2*((net displacement/minD)/PP). We studied a large group of patients with and without cardiovascular risk and conclude that DC using tissue Doppler correlates highly with DC by B-mode and M-mode imaging and is also very reproducible. In a subgroup, the vessel displacement values were “calibrated” using mean and diastolic pressure and with specialised software and a transfer function, central pressure wave forms were reconstructed. In this study we conclude that the central pressure obtained using tissue Doppler displacement of the carotid artery correlates highly with that obtained using applanation tonometry although there are technical challenges involved. With the known prognostic value of pulse pressure, chapter 6 explores whether there is added benefit to measuring total arterial compliance over pulse pressure alone. Once again patients with and without disease were studied and we conclude that brachial pulse pressure correlates well with TAC in men with normal cardiac function. However, in women and in patients at the low and high extremes of function, and in patients with preclinical and overt cardiovascular disease, there appears to be incremental value in measuring TAC. The role of cardiovascular risk factors in association with TAC is examined in chapter 7. Several studies have shown that TAC is lower in certain groups due to age, height, hypertension, hyperlipidaemia or other factors. We studied 720 patients with and without cardiovascular risk factors and did several multiple linear regression models based on anthropomorphic variables. Age was an independent correlate of TAC in most of the regression models and we conclude that TAC is associated with multiple risk factors, but age is a major determinant. The influence of age and other correlates may dwarf the contribution of individual risk factors and therefore their alteration with therapy. Chapter 8 examines the correlates of preclinical cardiovascular disease in both indigenous and non-indigenous Australians with and without diabetes mellitus (DM). DM is a major health problem in the Indigenous population in Australia and CVD occurs earlier in this group than in caucasians and is responsible for 1/3 of all deaths. We studied a large group of indigenous Australians with and without DM and matched them to a caucasian population. There were no differences in BAR between the groups probably due to large standard deviations in the measurements. In assessing DC, both DM groups had significantly lower DC than the non-DM groups. However, in the IMT analysis both of the indigenous groups had significantly higher IMT than their caucasian counterparts and even after IMT was corrected for age, Indigenous patients even at an early age had significantly higher IMT. We conclude that despite a high incidence of risk factors in indigenous Australians both with and without DM, ethnicity (and various other risk factors for which it is a marker) appears to be an independent predictor of preclinical cardiovascular disease. In chapter 3 we determined that TAC was not an independent correlate of patients either at risk of CAD or with CAD. Chapter 9 discusses the results of a study of patients presenting for stress echocardiography for either detection of CAD or risk stratification. Ischaemia was detected in 25% of cases and TAC was similar in those with and without ischaemia. In multiple linear regression models however, in addition to cardiovascular risk factors TAC was independently associated with both the presence of CAD and the extent of ischaemia at stress echocardiography. Several studies have used vascular function as an outcome measure in intervention trials, either lifestyle or pharmacologic. In chapter 10 we undertook a lifestyle and diet intervention study in a large group of healthy patients with type-II DM. The tests for IMT, BAR and TAC were used in addition to biochemical markers and fitness assessment. At follow-up the intervention group had significant changes in weight and BMI and significantly increased fitness but failed to show any changes in any of the vascular parameters. We conclude that while metabolic and fitness parameters respond to treatment in patients with type-II DM, the early changes seen in vascular structure, function and compliance may not change in the long term. Although TAC has been correlated with hypertension, LVH, myocardial ischaemia and heart failure there are few data existing regarding the relationship of TAC to outcome. In the final chapter of this thesis we sought whether TAC was predictive of outcome in a large, primary prevention group of patients with varying degrees of cardiovascular risk. We followed up 719 patients who were studied between 2001 and 2008 in Brisbane, Australia and examined TAC in relation to mortality and a composite endpoint of death or hospital admission. There were significant differences in groups having low and normal TAC for both death and the composite endpoint and in patients with intermediate and high Framingham 10-year risk TAC was an independent predictor of both death and the composite endpoint. We conclude that TAC correlates with outcome in patients with varying degrees of cardiovascular risk and also adds incremental benefit to Framingham risk alone in patients with intermediate risk.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-08-03T19:33:51Z No. of bitstreams: 1 Rogerio Jorge Barbosa Oliveira Incorporação e esterificação do colesterol na... 2012.pdf: 2467697 bytes, checksum: 40447b73cfb90f7a212555b74a8d0091 (MD5) / Made available in DSpace on 2012-08-03T19:33:51Z (GMT). No. of bitstreams: 1 Rogerio Jorge Barbosa Oliveira Incorporação e esterificação do colesterol na... 2012.pdf: 2467697 bytes, checksum: 40447b73cfb90f7a212555b74a8d0091 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / As complicações da aterosclerose agregam as principais causas de morte no mundo relacionada a problemas cardiovasculares. É caracterizada por distúrbio da condição mecânica e fisiológica, que promove espessamento e endurecimento nas ar tér i as coronárias, cerebrais e periféricos, ocasionando lesão inflamatória crônica, rica em lipídios e células características do processo inflamatório nas paredes vasculares. Objetivos: Avaliar concentrações plasmáticas de biomarcadores do metabolismo lipídico e resultados de doppler de carótidas, relacionando-os com a doença aterogênica de carótidas. Delineamento: Estudo de Corte Transverso. Casuística e Métodos: 66 pacientes com idade 57,5 ± 15,5 anos, (20 a 77), 63% mulheres. Na análise estatística utilizaram-se testes paramétricos e nãoparamétricos, valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: Verificou-se DCA na população masculina a partir da faixa 36-45 anos; nas mulheres, a doença pôde ser detectada a partir de 46-55 anos, elevando-se em ambos gêneros conforme aumento da idade. Tivemos maior prevalência de DCA no gênero feminino (33% contra apenas 15%), na faixa de 56-65 anos, mostrando RR de 1,56 para o gênero feminino (p<0,002; teste de Fisher, com aproximação de Katz). Quanto ao perfil clínico, houve prevalência de 53% pacientes com DCA; 82% pacientes estavam em uso de medicação regular para quaisquer das doenças pregressas; 68% hipertensos; 73% dislipidêmicos; 11% coronariopatas; 4% apresentaram AVE e 64% faziam uso regular de hipolipemiantes. O teste de Fisher evidenciou diferentes RR em função da presença ou não de DCA: Hipotireoidismo (DCA vs NDCA, p< 0,555; RR=1,0); (DCA vs EMI, p < 0,0001; RR=5,2); Dislipidemia (DCA vs NDCA, p< 0,001; RR=1,62); HAS (DCA vs NDCA, p< 0,003; RR=1,76); DM (DCA vs NDCA, p< 0,001; RR=3,6); AVE (DCA vs NDCA, p< 0,0001; RR=2,03); DAC (DCA vs NDCA, p< 0,0001; RR=6,14). Predominaram estenoses leves em 44%, estenoses moderadas em 9%, não foram observados pacientes com estenose severa ou oclusão. A avaliação dos dados de colesterol livre e total de colesterol marcado na fração HDL diferiu entre os grupos estratificados por HDL-C maior e menor do que 40mg/dl e para as condições DCA e sem DCA (p = 0,0409 e, p = 0,0475 teste t), respectivamente. A análise de correlação linear de Pearson entre os dados de atividade de PON1 quando HDL-C < 40mg/dl e incorporação de colesterol livre e, também entre percentual de esterificação CL/CE foi significativa (r = -0,6; p = 0,048; n = 20 e r = -0,7; p = 0,006; n = 12), respectivamente. Conclusões: Evidenciado presença da DCA com aumento da idade conforme literatura; prevaleceu DCA no perfil clínico dos participantes do estudo; as doenças de base identificadas elevam o risco para DCA; o transporte reverso de colesterol é prejudicado na DCA. / Atherosclerosis is the leading cause death worldwide related from cardiovascular. Atherosclerosis is characterized by disturbance of mechanical and physiological condition, which promotes thickening and hardening of the coronary vessels, cerebral and peripheral inflammatory lesion causing chronic high-fat and abnormal cells in vascular walls. Objectives: Assess plasma concentrations of biomarkers of lipid metabolism and vascular echocardiography results of carotid artery linking them with the disease of the carotid atherogenic. Delineation: Cross-sectional observational study. Casuistry and Methods: 66 patients aged 57.5 ± 15.5 years (20-77), 63% female. Were used in the statistical analysis parametric tests and non-parametric, p-values <0.05 was considered significant. Results: It was found in the DCA from the male population age 36-45 years, in women, the disease could be detected from 46-55 years, rising in both genders as age increases. We had a higher prevalence of DCA among females (33% versus 15%), range 56-65 years, showing an RR of 1.56 for females (p <0.002, Fisher's test with approximation of Katz). As the clinical profile, there was prevalence from 53% patients with DCA, 82% patients were taking regular medication for any of the previous diseases, 68% hypertensive, 73% had dyslipidemia, and of those, 53% had evidence of DCA associated with. Coronary artery disease 11%, 4% had stroke and 64% were regularly taking lipid-lowering. The Fisher test showed different RR due to the presence or absence of DCA: The Fisher test showed different RR due to the presence or absence of DCA: Hypothyroidism (DCA vs NDCA, p <0.555, RR = 1.0), (DCA vs. EMI, p <0.0001, RR = 5.2) ; Dyslipidemia (DCA vs NDCA, p <0.001, RR = 1.62), hypertension (DCA vs NDCA, p <0.003, RR = 1.76), DM (DCA vs NDCA, p <0.001, RR = 3.6 ), stroke (DCA vs NDCA, p <0.0001, RR = 2.03), DAC (DCA vs NDCA, p <0.0001, RR = 6.14). Mild stenosis predominated in 44%, moderate stenosis in 9%. Were not seen patients with severe stenosis or occlusion. The evaluation of data from free cholesterol and total cholesterol HDL fraction differed marked on stratified groups and increased HDL-C less than 40mg/dl and conditions and without DCA (p = 0.0409 and p = 0, 0475 t-test), respectively. The analysis of Pearson's linear correlation between the data of PON1 activity when HDL-C <40mg/dl and incorporation of free cholesterol, and also between percentage of esterification CL / CE was significant (r = -0.6, p = 0.048 n = 20 and r = -0.7, p = 0.006, n = 12), respectively. Conclusions: Evidenced presence of DCA with increasing age according to the literature, DCA prevailed in the clinical profile of study participants, underlying diseases increase the risk identified for DCA, the reverse is impaired in DCA.

Os efeitos adversos à saúde desencadeados pela exposição à poluição atmosférica estão sendo muito discutidos. Estudos têm mostrado associações entre a exposição a poluentes atmosféricos, especialmente ao material particulado, e doenças cardiovasculares. Estas partículas, por sua vez, possuem diversas substâncias tóxicas adsorvidas, como os hidrocarbonetos policíclicos aromáticos (HPAs) e metais. O metabólito urinário 1-hidroxipireno tem sido utilizado como um biomarcador para avaliar a exposição aos HPAs presentes no ambiente urbano originados pela emissão veicular. Neste trabalho, foi avaliada a exposição ocupacional aos xenobióticos ambientais e sua inter-relação com a inflamação/aterosclerose e danos oxidativos. Os grupos de estudo deste trabalho foram constituídos por taxistas da cidade de Porto Alegre e indivíduos com atividades administrativas (controles). Neste sentido, a exposição ocupacional aos poluentes ambientais foi avaliada através da quantificação dos biomarcadores de exposição e efeito. Além disso, foram quantificados os níveis de Hcy, ox-LDL e ox-LDL-Ab e a medida da espessura das camadas íntima e média das carótidas (EIMC) pelo exame de ultrassom. Adicionalmente, metais foram quantificados tanto no material particulado como no sangue dos participantes deste estudo. Em relação ao material particulado 2,5 μm foi observada uma concentração média de 12.4 ± 6.9 μg m-3. No capítulo I, verificou-se que os níveis de 1-hidroxipireno estavam aumentados nos taxistas em comparação ao grupo controle (p<0,05). Os mediadores inflamatórios, a peroxidação lipídica, a oxidação de proteínas, bem como os níveis de Hcy, ox-LDL e ox-LDL-Ab também estavam aumentados (p<0,05) e as atividades das enzimas catalase, glutationa peroxidase e glutationa S-transferase estavam diminuídas nos taxistas quando comparadas ao grupo controle (p<0,05). O 1-hidroxipireno foi positivamente associado com os biomarcadores inflamatórios (IL-1β, IL-6 e TNF-α) e negativamente associado com as enzimas antioxidantes (catalase e glutationa S-transferase) (p<0,05). No capítulo II, os resultados demonstraram que os taxistas com comorbidades apresentaram maiores níveis de EIMC em comparação aos taxistas sem comorbidades, porém considerando apenas os taxistas sem comorbidades, 15% apresentaram EIMC acima dos valores de referência. Além disso, observou-se associações positivas entre os níveis de 1-hidroxipireno com Hcy e EIMC (p<0,05). No capítulo III, foi avaliado os níveis sanguíneos dos metais tóxicos e essenciais, bem como sua potencial influência sobre o processo inflamatório, status oxidativo e a função renal. Verificou-se que as concentrações sanguíneas de Hg, As, Pb e Cd estavam aumentadas, enquanto que os níveis de Se, Cu e Zn estavam diminuídos nos taxistas quando comparadas ao grupo controle (p<0,05). Adicionalmente, os níveis de Hg, As e Pb apresentaram associações positivas com as citocinas, Hcy e com o tempo de exposição ocupacional e negativamente com a glutationa peroxidase. Em conjunto, os dados desta tese indicam que os taxistas expostos ocupacionalmente aos poluentes ambientais apresentam elevados níveis de mediadores inflamatórios, danos oxidativos lipídico e proteico, diminuição das enzimas antioxidantes e alteração nos níveis de Hcy, ox-LDL e ox-LDL-Ab. Os resultados indicam que os taxistas apresentam uma maior exposição aos HPAs, comparados aos controles, sendo que esta exposição foi associada diretamente com a inflamação e aterosclerose. Os níveis de Hg, As e Pb também foram associados com inflamação e aterosclerose, porém outras fontes de exposição ambiental a estes xenobióticos precisam ser investigadas. Os taxistas avaliados estão mais propensos a apresentar doenças crônicas, como aterosclerose, relacionadas as múltiplas interações da exposição ocupacional e ambiental à poluição atmosférica. Diante dos resultados, este trabalho demonstrou o papel da poluição contribuindo com a inflamação/aterosclerose que representam importantes preditores para eventos cardiovasculares. / The adverse effects in human health caused by the exposure to air pollutants have been receiving much discussion. Studies have shown an association between exposure to environmental pollutants, especially to airborne particulate matter, and cardiovascular events. These particles contain various chemical compounds adsorbed to their surfaces, such as polycyclic aromatic hydrocarbons (PAHs) and metals. Urinary metabolite 1-hydroxypyrene is a biomarker used to assess exposure to PAHs in the urban environment generated by vehicular emission. The present study aimed to evaluate the occupational exposure to environmental xenobiotics and its relationship with inflammation/atherosclerosis and oxidative damage. The study population was comprised of taxi drivers and office workers (controls) resident in the city of Porto Alegre. The occupational exposure to environmental pollutants was assessed through the measurement of biomarkers of exposure and effect. In addition, we also analyzed the levels of Hcy, ox-LDL and ox-LDL-Ab and the measurement of carotid intima-media thickness (CIMT) by ultrasound imaging. Additionally, metals were measured in particulate matter and blood samples. In relation to the 2.5 μm particulate matter (PM2.5), we found a mean concentration of 12.4 ± 6.9 μg m-3. In the first chapter, we demonstrated that 1-hydroxypyrene levels were increased in taxi drivers compared to the control group (p<0.05). The inflammatory mediators, lipid peroxidation, protein oxidation as well as Hcy, ox-LDL and ox-LDL-Ab levels were also increased (p<0.05) and catalase, glutathione peroxidase and glutathione S-transferase activities were decreased in taxi drivers (p<0.05). 1-Hydroxypyrene levels were positively associated to inflammatory biomarkers (IL-1β, IL-6 and TNF-α) and were negatively associated to antioxidants enzymes (catalase and glutathione S-transferase) (p<0.05). In the chapter II, our results showed that taxi drivers with co-morbidities had higher CIMT levels compared to taxi drivers without co-morbidities; however, considering only taxi drivers without co-morbidities, 15% showed CIMT above the reference values. Moreover, we found that 1-hydroxypyrene levels were positively associated to Hcy and CIMT (p<0.05). In chapter III, we evaluated toxic and essential blood metals and their potential influence on the inflammatory process, oxidative status and renal function. We observed that the levels of Hg, As Pb and Cd in blood were increased and Se, Cu and Zn levels were diminished in taxi drivers compared to the control group (p<0.05). Additionally, Hg, As and Pb levels showed positive associations to cytokines, Hcy and years of work, and negative associations to glutathione peroxidase. Taken together, all data from this thesis indicate that taxi drivers occupationally exposed to environmental pollutants showed elevation of inflammatory mediators, lipid and protein oxidative damages, decreased antioxidant enzymes and enhanced Hcy, ox-LDL and ox-LDL-Ab levels. PAH exposure was higher in taxi drivers compared to controls, and was directly associated to inflammation and atherosclerosis. Hg, As and Pb levels were also associated to inflammation and atherosclerosis, but other sources of environmental exposure to these xenobiotics need to be investigated. Taxi drivers were more susceptible to the development of chronic diseases, such as atherosclerosis, which were related to the multiple interactions of environmental and occupational exposure to air pollution. In summary, this study demonstrated the role of air pollution in contributing to the induction of inflammation/atherosclerosis in taxi drivers, representing important predictors for cardiovascular events.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A periodontite é uma doença infecciosa, crônica e altamente prevalente causando uma resposta inflamatória. A infecção e a inflamação são consideradas a base etiológica para o desenvolvimento da aterosclerose. Recentes estudos indicam que a periodontite severa pode influenciar o aumento de marcadores inflamatórios e de disfunção endotelial associados com o aumento de risco da doença coronariana e o acidente vascular cerebral. Embora alguns estudos tenham sugerido esta associação, os reais efeitos do tratamento da doença periodontal sobre a rede complexa de marcadores envolvidos na aterosclerose são pouco conhecidos. O objetivo deste estudo foi avaliar o efeito da terapia periodontal nos biomarcadores inflamatórios (TNF-&#945;, fibrinogênio, PCRus, INF&#947;, IL-1&#946;, IL-6 e IL-10), perfil lipídico (CT, HDL, LDL, TG, oxLDL e anti-oxLDL) e função endotelial (IMT) das artérias carótidas. Um total de trinta e dois indivíduos saudáveis sistemicamente e afetados pela periodontite severa (16 mulheres, 16 homens; 51,87 anos de idade), incluindo 17 sujeitos para o grupo teste e 15 sujeitos para o grupo controle foram recrutados para o estudo. A ultrassonografia das artérias carótidas e os níveis séricos inflamatórios foram avaliados no início, 40 e 100 dias após o tratamento periodontal não-cirúrgico, comparando tempo e grupos. O tratamento periodontal resultou em significante redução dos parâmetros da doença periodontal. O grupo que recebeu tratamento mostrou decréscimos significativos de oxLDL (P<0.0001), anti-oxLDL (P<0,0001), TNF-&#945; (P<0,0001), fibrinogênio (P=0,008), INF&#947; (P<0,0001), IL-1&#946; (P<0,0001), IL-6 (P<0,0001), IMT (P=0,006) e significante aumento de IL-10 (P<0,0001) após 100 dias do tratamento periodontal comparando com grupo controle. Entretanto, os resultados não foram significativos para PCRu (P=0,109), colesterol total (P=0,438), HDL (P=0,119), LDL (P=0,425) e triglicerídeos (P=0,939). Com base nestes resultados, o tratamento da periodontite pode melhorar o perfil inflamatório e a função endotelial, sendo uma importante ferramenta adicional para a prevenção das doenças cardiovasculares. / Periodontitis is an infectious, chronic and highly prevalente that causes an inflammatory response. Infection and inflammation are considered to be the etiological basis for the development of atherosclerosis. Recent studies indicate that severe periodontitis may influence the increased inflammatory and endotelial dysfunction markers associated with increased risk of coronary heart disease and stroke. Although some studies have suggested this association, the true effects of periodontal treatment on the complex novel of markers involved in atherosclerosis are poorly understood. The aim of this study was to evaluate the effect of periodontal therapy on inflammatory biomarkers (TNF-&#945;, fibrinogen, PCRus, INF&#947;, IL-1&#946;, IL-6 and IL-10), lipid profile (TC, HDL, LDL, TG, oxLDL and anti-oxLDL) and endothelial function (IMT) of carotid arteries. A total of thirty-two otherwise health individuals affected by severe periodontitis (16 women, 16 man; 51,87 years old), including 17 subjects for the test group and 15 subjects in the control group, were enrolled in the study. Echo-Doppler cardiography of the carotid artery and plasma inflammatory indices were evaluated at baseline, 40 and 100 days after non-surgical periodontal treatment. Periodontal treatment resulted in a significant reduction of parameters of periodontal disease. The test group showed significant decreases in oxLDL (P<0.0001), anti-oxLDL (P<0,0001), TNF-&#945; (P<0,0001), fibrinogen (P=0,008), INF&#947; (P<0,0001), IL-1&#946; (P<0,0001), IL-6 (P<0,0001), IMT (P=0,006) and significant increase of IL-10 (P<0,0001) after 100 days of periodontal treatment compared with control group. However, the results were not significant for PCRu (P=0,109), total colesterol (P=0,438), HDL colesterol (P=0,119), LDL colesterol (P=0,425) and tryglicerides (P=0,939). Based on these results, treating periodontitis can improve endotelial function and inflammatory profile being an important preventive tool for cardiovascular disease.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A periodontite é uma doença infecciosa, crônica e altamente prevalente causando uma resposta inflamatória. A infecção e a inflamação são consideradas a base etiológica para o desenvolvimento da aterosclerose. Recentes estudos indicam que a periodontite severa pode influenciar o aumento de marcadores inflamatórios e de disfunção endotelial associados com o aumento de risco da doença coronariana e o acidente vascular cerebral. Embora alguns estudos tenham sugerido esta associação, os reais efeitos do tratamento da doença periodontal sobre a rede complexa de marcadores envolvidos na aterosclerose são pouco conhecidos. O objetivo deste estudo foi avaliar o efeito da terapia periodontal nos biomarcadores inflamatórios (TNF-&#945;, fibrinogênio, PCRus, INF&#947;, IL-1&#946;, IL-6 e IL-10), perfil lipídico (CT, HDL, LDL, TG, oxLDL e anti-oxLDL) e função endotelial (IMT) das artérias carótidas. Um total de trinta e dois indivíduos saudáveis sistemicamente e afetados pela periodontite severa (16 mulheres, 16 homens; 51,87 anos de idade), incluindo 17 sujeitos para o grupo teste e 15 sujeitos para o grupo controle foram recrutados para o estudo. A ultrassonografia das artérias carótidas e os níveis séricos inflamatórios foram avaliados no início, 40 e 100 dias após o tratamento periodontal não-cirúrgico, comparando tempo e grupos. O tratamento periodontal resultou em significante redução dos parâmetros da doença periodontal. O grupo que recebeu tratamento mostrou decréscimos significativos de oxLDL (P<0.0001), anti-oxLDL (P<0,0001), TNF-&#945; (P<0,0001), fibrinogênio (P=0,008), INF&#947; (P<0,0001), IL-1&#946; (P<0,0001), IL-6 (P<0,0001), IMT (P=0,006) e significante aumento de IL-10 (P<0,0001) após 100 dias do tratamento periodontal comparando com grupo controle. Entretanto, os resultados não foram significativos para PCRu (P=0,109), colesterol total (P=0,438), HDL (P=0,119), LDL (P=0,425) e triglicerídeos (P=0,939). Com base nestes resultados, o tratamento da periodontite pode melhorar o perfil inflamatório e a função endotelial, sendo uma importante ferramenta adicional para a prevenção das doenças cardiovasculares. / Periodontitis is an infectious, chronic and highly prevalente that causes an inflammatory response. Infection and inflammation are considered to be the etiological basis for the development of atherosclerosis. Recent studies indicate that severe periodontitis may influence the increased inflammatory and endotelial dysfunction markers associated with increased risk of coronary heart disease and stroke. Although some studies have suggested this association, the true effects of periodontal treatment on the complex novel of markers involved in atherosclerosis are poorly understood. The aim of this study was to evaluate the effect of periodontal therapy on inflammatory biomarkers (TNF-&#945;, fibrinogen, PCRus, INF&#947;, IL-1&#946;, IL-6 and IL-10), lipid profile (TC, HDL, LDL, TG, oxLDL and anti-oxLDL) and endothelial function (IMT) of carotid arteries. A total of thirty-two otherwise health individuals affected by severe periodontitis (16 women, 16 man; 51,87 years old), including 17 subjects for the test group and 15 subjects in the control group, were enrolled in the study. Echo-Doppler cardiography of the carotid artery and plasma inflammatory indices were evaluated at baseline, 40 and 100 days after non-surgical periodontal treatment. Periodontal treatment resulted in a significant reduction of parameters of periodontal disease. The test group showed significant decreases in oxLDL (P<0.0001), anti-oxLDL (P<0,0001), TNF-&#945; (P<0,0001), fibrinogen (P=0,008), INF&#947; (P<0,0001), IL-1&#946; (P<0,0001), IL-6 (P<0,0001), IMT (P=0,006) and significant increase of IL-10 (P<0,0001) after 100 days of periodontal treatment compared with control group. However, the results were not significant for PCRu (P=0,109), total colesterol (P=0,438), HDL colesterol (P=0,119), LDL colesterol (P=0,425) and tryglicerides (P=0,939). Based on these results, treating periodontitis can improve endotelial function and inflammatory profile being an important preventive tool for cardiovascular disease.

Os efeitos adversos à saúde desencadeados pela exposição à poluição atmosférica estão sendo muito discutidos. Estudos têm mostrado associações entre a exposição a poluentes atmosféricos, especialmente ao material particulado, e doenças cardiovasculares. Estas partículas, por sua vez, possuem diversas substâncias tóxicas adsorvidas, como os hidrocarbonetos policíclicos aromáticos (HPAs) e metais. O metabólito urinário 1-hidroxipireno tem sido utilizado como um biomarcador para avaliar a exposição aos HPAs presentes no ambiente urbano originados pela emissão veicular. Neste trabalho, foi avaliada a exposição ocupacional aos xenobióticos ambientais e sua inter-relação com a inflamação/aterosclerose e danos oxidativos. Os grupos de estudo deste trabalho foram constituídos por taxistas da cidade de Porto Alegre e indivíduos com atividades administrativas (controles). Neste sentido, a exposição ocupacional aos poluentes ambientais foi avaliada através da quantificação dos biomarcadores de exposição e efeito. Além disso, foram quantificados os níveis de Hcy, ox-LDL e ox-LDL-Ab e a medida da espessura das camadas íntima e média das carótidas (EIMC) pelo exame de ultrassom. Adicionalmente, metais foram quantificados tanto no material particulado como no sangue dos participantes deste estudo. Em relação ao material particulado 2,5 μm foi observada uma concentração média de 12.4 ± 6.9 μg m-3. No capítulo I, verificou-se que os níveis de 1-hidroxipireno estavam aumentados nos taxistas em comparação ao grupo controle (p<0,05). Os mediadores inflamatórios, a peroxidação lipídica, a oxidação de proteínas, bem como os níveis de Hcy, ox-LDL e ox-LDL-Ab também estavam aumentados (p<0,05) e as atividades das enzimas catalase, glutationa peroxidase e glutationa S-transferase estavam diminuídas nos taxistas quando comparadas ao grupo controle (p<0,05). O 1-hidroxipireno foi positivamente associado com os biomarcadores inflamatórios (IL-1β, IL-6 e TNF-α) e negativamente associado com as enzimas antioxidantes (catalase e glutationa S-transferase) (p<0,05). No capítulo II, os resultados demonstraram que os taxistas com comorbidades apresentaram maiores níveis de EIMC em comparação aos taxistas sem comorbidades, porém considerando apenas os taxistas sem comorbidades, 15% apresentaram EIMC acima dos valores de referência. Além disso, observou-se associações positivas entre os níveis de 1-hidroxipireno com Hcy e EIMC (p<0,05). No capítulo III, foi avaliado os níveis sanguíneos dos metais tóxicos e essenciais, bem como sua potencial influência sobre o processo inflamatório, status oxidativo e a função renal. Verificou-se que as concentrações sanguíneas de Hg, As, Pb e Cd estavam aumentadas, enquanto que os níveis de Se, Cu e Zn estavam diminuídos nos taxistas quando comparadas ao grupo controle (p<0,05). Adicionalmente, os níveis de Hg, As e Pb apresentaram associações positivas com as citocinas, Hcy e com o tempo de exposição ocupacional e negativamente com a glutationa peroxidase. Em conjunto, os dados desta tese indicam que os taxistas expostos ocupacionalmente aos poluentes ambientais apresentam elevados níveis de mediadores inflamatórios, danos oxidativos lipídico e proteico, diminuição das enzimas antioxidantes e alteração nos níveis de Hcy, ox-LDL e ox-LDL-Ab. Os resultados indicam que os taxistas apresentam uma maior exposição aos HPAs, comparados aos controles, sendo que esta exposição foi associada diretamente com a inflamação e aterosclerose. Os níveis de Hg, As e Pb também foram associados com inflamação e aterosclerose, porém outras fontes de exposição ambiental a estes xenobióticos precisam ser investigadas. Os taxistas avaliados estão mais propensos a apresentar doenças crônicas, como aterosclerose, relacionadas as múltiplas interações da exposição ocupacional e ambiental à poluição atmosférica. Diante dos resultados, este trabalho demonstrou o papel da poluição contribuindo com a inflamação/aterosclerose que representam importantes preditores para eventos cardiovasculares. / The adverse effects in human health caused by the exposure to air pollutants have been receiving much discussion. Studies have shown an association between exposure to environmental pollutants, especially to airborne particulate matter, and cardiovascular events. These particles contain various chemical compounds adsorbed to their surfaces, such as polycyclic aromatic hydrocarbons (PAHs) and metals. Urinary metabolite 1-hydroxypyrene is a biomarker used to assess exposure to PAHs in the urban environment generated by vehicular emission. The present study aimed to evaluate the occupational exposure to environmental xenobiotics and its relationship with inflammation/atherosclerosis and oxidative damage. The study population was comprised of taxi drivers and office workers (controls) resident in the city of Porto Alegre. The occupational exposure to environmental pollutants was assessed through the measurement of biomarkers of exposure and effect. In addition, we also analyzed the levels of Hcy, ox-LDL and ox-LDL-Ab and the measurement of carotid intima-media thickness (CIMT) by ultrasound imaging. Additionally, metals were measured in particulate matter and blood samples. In relation to the 2.5 μm particulate matter (PM2.5), we found a mean concentration of 12.4 ± 6.9 μg m-3. In the first chapter, we demonstrated that 1-hydroxypyrene levels were increased in taxi drivers compared to the control group (p<0.05). The inflammatory mediators, lipid peroxidation, protein oxidation as well as Hcy, ox-LDL and ox-LDL-Ab levels were also increased (p<0.05) and catalase, glutathione peroxidase and glutathione S-transferase activities were decreased in taxi drivers (p<0.05). 1-Hydroxypyrene levels were positively associated to inflammatory biomarkers (IL-1β, IL-6 and TNF-α) and were negatively associated to antioxidants enzymes (catalase and glutathione S-transferase) (p<0.05). In the chapter II, our results showed that taxi drivers with co-morbidities had higher CIMT levels compared to taxi drivers without co-morbidities; however, considering only taxi drivers without co-morbidities, 15% showed CIMT above the reference values. Moreover, we found that 1-hydroxypyrene levels were positively associated to Hcy and CIMT (p<0.05). In chapter III, we evaluated toxic and essential blood metals and their potential influence on the inflammatory process, oxidative status and renal function. We observed that the levels of Hg, As Pb and Cd in blood were increased and Se, Cu and Zn levels were diminished in taxi drivers compared to the control group (p<0.05). Additionally, Hg, As and Pb levels showed positive associations to cytokines, Hcy and years of work, and negative associations to glutathione peroxidase. Taken together, all data from this thesis indicate that taxi drivers occupationally exposed to environmental pollutants showed elevation of inflammatory mediators, lipid and protein oxidative damages, decreased antioxidant enzymes and enhanced Hcy, ox-LDL and ox-LDL-Ab levels. PAH exposure was higher in taxi drivers compared to controls, and was directly associated to inflammation and atherosclerosis. Hg, As and Pb levels were also associated to inflammation and atherosclerosis, but other sources of environmental exposure to these xenobiotics need to be investigated. Taxi drivers were more susceptible to the development of chronic diseases, such as atherosclerosis, which were related to the multiple interactions of environmental and occupational exposure to air pollution. In summary, this study demonstrated the role of air pollution in contributing to the induction of inflammation/atherosclerosis in taxi drivers, representing important predictors for cardiovascular events.

Os efeitos adversos à saúde desencadeados pela exposição à poluição atmosférica estão sendo muito discutidos. Estudos têm mostrado associações entre a exposição a poluentes atmosféricos, especialmente ao material particulado, e doenças cardiovasculares. Estas partículas, por sua vez, possuem diversas substâncias tóxicas adsorvidas, como os hidrocarbonetos policíclicos aromáticos (HPAs) e metais. O metabólito urinário 1-hidroxipireno tem sido utilizado como um biomarcador para avaliar a exposição aos HPAs presentes no ambiente urbano originados pela emissão veicular. Neste trabalho, foi avaliada a exposição ocupacional aos xenobióticos ambientais e sua inter-relação com a inflamação/aterosclerose e danos oxidativos. Os grupos de estudo deste trabalho foram constituídos por taxistas da cidade de Porto Alegre e indivíduos com atividades administrativas (controles). Neste sentido, a exposição ocupacional aos poluentes ambientais foi avaliada através da quantificação dos biomarcadores de exposição e efeito. Além disso, foram quantificados os níveis de Hcy, ox-LDL e ox-LDL-Ab e a medida da espessura das camadas íntima e média das carótidas (EIMC) pelo exame de ultrassom. Adicionalmente, metais foram quantificados tanto no material particulado como no sangue dos participantes deste estudo. Em relação ao material particulado 2,5 μm foi observada uma concentração média de 12.4 ± 6.9 μg m-3. No capítulo I, verificou-se que os níveis de 1-hidroxipireno estavam aumentados nos taxistas em comparação ao grupo controle (p<0,05). Os mediadores inflamatórios, a peroxidação lipídica, a oxidação de proteínas, bem como os níveis de Hcy, ox-LDL e ox-LDL-Ab também estavam aumentados (p<0,05) e as atividades das enzimas catalase, glutationa peroxidase e glutationa S-transferase estavam diminuídas nos taxistas quando comparadas ao grupo controle (p<0,05). O 1-hidroxipireno foi positivamente associado com os biomarcadores inflamatórios (IL-1β, IL-6 e TNF-α) e negativamente associado com as enzimas antioxidantes (catalase e glutationa S-transferase) (p<0,05). No capítulo II, os resultados demonstraram que os taxistas com comorbidades apresentaram maiores níveis de EIMC em comparação aos taxistas sem comorbidades, porém considerando apenas os taxistas sem comorbidades, 15% apresentaram EIMC acima dos valores de referência. Além disso, observou-se associações positivas entre os níveis de 1-hidroxipireno com Hcy e EIMC (p<0,05). No capítulo III, foi avaliado os níveis sanguíneos dos metais tóxicos e essenciais, bem como sua potencial influência sobre o processo inflamatório, status oxidativo e a função renal. Verificou-se que as concentrações sanguíneas de Hg, As, Pb e Cd estavam aumentadas, enquanto que os níveis de Se, Cu e Zn estavam diminuídos nos taxistas quando comparadas ao grupo controle (p<0,05). Adicionalmente, os níveis de Hg, As e Pb apresentaram associações positivas com as citocinas, Hcy e com o tempo de exposição ocupacional e negativamente com a glutationa peroxidase. Em conjunto, os dados desta tese indicam que os taxistas expostos ocupacionalmente aos poluentes ambientais apresentam elevados níveis de mediadores inflamatórios, danos oxidativos lipídico e proteico, diminuição das enzimas antioxidantes e alteração nos níveis de Hcy, ox-LDL e ox-LDL-Ab. Os resultados indicam que os taxistas apresentam uma maior exposição aos HPAs, comparados aos controles, sendo que esta exposição foi associada diretamente com a inflamação e aterosclerose. Os níveis de Hg, As e Pb também foram associados com inflamação e aterosclerose, porém outras fontes de exposição ambiental a estes xenobióticos precisam ser investigadas. Os taxistas avaliados estão mais propensos a apresentar doenças crônicas, como aterosclerose, relacionadas as múltiplas interações da exposição ocupacional e ambiental à poluição atmosférica. Diante dos resultados, este trabalho demonstrou o papel da poluição contribuindo com a inflamação/aterosclerose que representam importantes preditores para eventos cardiovasculares. / The adverse effects in human health caused by the exposure to air pollutants have been receiving much discussion. Studies have shown an association between exposure to environmental pollutants, especially to airborne particulate matter, and cardiovascular events. These particles contain various chemical compounds adsorbed to their surfaces, such as polycyclic aromatic hydrocarbons (PAHs) and metals. Urinary metabolite 1-hydroxypyrene is a biomarker used to assess exposure to PAHs in the urban environment generated by vehicular emission. The present study aimed to evaluate the occupational exposure to environmental xenobiotics and its relationship with inflammation/atherosclerosis and oxidative damage. The study population was comprised of taxi drivers and office workers (controls) resident in the city of Porto Alegre. The occupational exposure to environmental pollutants was assessed through the measurement of biomarkers of exposure and effect. In addition, we also analyzed the levels of Hcy, ox-LDL and ox-LDL-Ab and the measurement of carotid intima-media thickness (CIMT) by ultrasound imaging. Additionally, metals were measured in particulate matter and blood samples. In relation to the 2.5 μm particulate matter (PM2.5), we found a mean concentration of 12.4 ± 6.9 μg m-3. In the first chapter, we demonstrated that 1-hydroxypyrene levels were increased in taxi drivers compared to the control group (p<0.05). The inflammatory mediators, lipid peroxidation, protein oxidation as well as Hcy, ox-LDL and ox-LDL-Ab levels were also increased (p<0.05) and catalase, glutathione peroxidase and glutathione S-transferase activities were decreased in taxi drivers (p<0.05). 1-Hydroxypyrene levels were positively associated to inflammatory biomarkers (IL-1β, IL-6 and TNF-α) and were negatively associated to antioxidants enzymes (catalase and glutathione S-transferase) (p<0.05). In the chapter II, our results showed that taxi drivers with co-morbidities had higher CIMT levels compared to taxi drivers without co-morbidities; however, considering only taxi drivers without co-morbidities, 15% showed CIMT above the reference values. Moreover, we found that 1-hydroxypyrene levels were positively associated to Hcy and CIMT (p<0.05). In chapter III, we evaluated toxic and essential blood metals and their potential influence on the inflammatory process, oxidative status and renal function. We observed that the levels of Hg, As Pb and Cd in blood were increased and Se, Cu and Zn levels were diminished in taxi drivers compared to the control group (p<0.05). Additionally, Hg, As and Pb levels showed positive associations to cytokines, Hcy and years of work, and negative associations to glutathione peroxidase. Taken together, all data from this thesis indicate that taxi drivers occupationally exposed to environmental pollutants showed elevation of inflammatory mediators, lipid and protein oxidative damages, decreased antioxidant enzymes and enhanced Hcy, ox-LDL and ox-LDL-Ab levels. PAH exposure was higher in taxi drivers compared to controls, and was directly associated to inflammation and atherosclerosis. Hg, As and Pb levels were also associated to inflammation and atherosclerosis, but other sources of environmental exposure to these xenobiotics need to be investigated. Taxi drivers were more susceptible to the development of chronic diseases, such as atherosclerosis, which were related to the multiple interactions of environmental and occupational exposure to air pollution. In summary, this study demonstrated the role of air pollution in contributing to the induction of inflammation/atherosclerosis in taxi drivers, representing important predictors for cardiovascular events.

Muito se conhece sobre os efeitos deletérios da poluição do ar, e a sua influência sobre a mortalidade e morbidade por problemas respiratórios e também por doenças cardiovasculares. Diversos métodos têm sido estudados no sentido de se avaliar as consequências da exposição aos poluentes atmosféricos sobre a saúde humana, bem como, tentar estabelecer os mecanismos que envolvem esta relação. Dados antropométricos, exames de imagem e marcadores laboratoriais têm sido utilizados no sentido de se investigar o desenvolvimento de doença aterosclerótica e, a partir daí, tentar estabelecer uma relação entre os fatores de risco, dentre eles, os poluentes atmosféricos e a aterogênese. Sabe-se que a medida ultrassonográfica da espessura da camada íntima - média das artérias carótidas (EIMC) - tem sido descrita como uma análise complementar de grande potencial na avaliação não invasiva da atividade inflamatória vascular, da gênese e do desenvolvimento da doença aterosclerótica, sendo considerado um preditor independente de risco para morbidade e mortalidade por causas cardiovasculares. Este projeto de pesquisa utilizou o banco de dados relativos ao estado de São Paulo do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil) e teve por objetivo investigar os possíveis efeitos da poluição atmosférica produzida pelo tráfego veicular na EIMC nos sujeitos incluídos neste projeto. A mensuração da exposição aos poluentes foi feita por meio de medidas indiretas utilizando-se a densidade de tráfego veicular dos locais georreferenciados (local de trabalho e domicílio), a distância da residência dos sujeitos do estudo em relação a vias de grande fluxo de veículos e, ainda, a distância percorrida no deslocamento dos sujeitos entre o domicílio e o local trabalho. Foi realizado um estudo de corte transversal com o modelo de regressão linear univariado e multivariado para se avaliar a possível correlação entre a exposição aos poluentes do ar e espessura da íntima média das carótidas (EIMC) / Air pollution has been well known to have deleterious effects, which leads to mortality and morbidity due to respiratory problems and cardiovascular diseases. Several methods have been used to evaluate the consequences of exposure to air pollutants on human health, to identify the mechanisms involving this relationship. Anthropometric data, imaging studies, and laboratory markers have been used to investigate the development of atherosclerotic disease and, based on this, we tried to identify the relationship between the risk factors, such as atmospheric pollutants and atherogenesis. Ultrasound measurement of the carotid intima-media thickness (CIMT) has been potentially described as a great complementary analysis in noninvasive assessment of vascular inflammatory activity, onset, and development of atherosclerotic disease, and is considered an independent predictor of risk for morbidity and mortality due to cardiovascular diseases. The database from the Longitudinal Study of Adult Health (ELSA-Brasil) in São Paulo was used in this study, to investigate the possible effects of air pollution produced by vehicular traffic in the CIMT of the subjects. The measurement of exposure to air pollutants was made through indirect measures of the density of vehicular traffic of georeferenced locations (work and home), the distance from the subjects\' residence to high traffic flow areas, as well as the distance covered during subjects\' commuting from their homes to workplace. A cross-sectional study using the univariate and multivariate linear regression models was conducted to evaluate the possible correlation between exposure to air pollutants and CIMT

Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Attempts have been made to inhibit intimal hyperplasia of the arteries with cilostazol and other drugs. Therefore, it is important to address the following research question: what is the difference between the mean of post-angioplasty myointimal thickening in the iliac artery of rabbits treated with A. sativum and that treated with cilostazol? Our objective is to determine the mean difference of post-angioplasty myointimal hyperplasia in the external iliac artery of rabbits with induced atherosclerosis, and compare the outcome between treatment with A. sativum and treatment with cilostazol. This is a randomized preclinical trial study conducted in experimental animals. We used female New Zealand rabbits (Oryctolagus cuniculus), submitted to an atherosclerotic diet and angioplasty of the external iliac artery. The animals were divided into the following groups (n = 10 each) according to treatment: group A, A. sativum, 800 μg⋅kg-1⋅day-1, orally; group C, cilostazol, 50 mg/day, orally; group S, 10 mL of 0.9% physiological saline solution, orally. Our primary variable is the difference of the mean myointimal hyperplasia. The secondary variable is the mean plate thickness of the arterial wall. Complementary data include frequency of limb ischemia, limb loss frequency, frequency of hematoma or bruising, frequency of infection, frequency of bleeding, frequency of animal death, and mean of lipid levels. The sample size was arbitrated in 30 rabbits. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the χ2 test. We calculated the 95% confidence interval (CI) for each point estimate, and the P value was set as < 0.05. Group S had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P < 0.0001. In conclution the Allium sativum quite as effective in inhibiting myointimal hyperplasia compared with those treated with cilostazol. / A hiperplasia intimal está relacionada à falha de enxertos e suturas vasculares no primeiro ano pós-cirurgia e nas reestenoses pós-angioplastia. O Allium sativum (alho comum) reduz o colesterol e tem efeito antioxidante, antiplaquetário e antitumoral; logo havia grande possibilidade de reduzir ou inibir a hiperplasia da íntima das artérias, a qual sua inibição vem sendo tentada com o Cilostazol e outros tratamentos. Sendo assim é relevante responder a pergunta de pesquisa: qual a diferença de média de hiperplasia miointimal pós-angioplastia na artéria ilíaca de coelhos tratados com Allium sativum comparada aos tratados com Cilostazol? O objetivo é determinar a diferença de média de hiperplasia miointimal pós-angioplastia na artéria ilíaca externa de coelhos com aterosclerose induzida e tratados com Allium sativum comparada aos tratados com Cilostazol. O estudo foi um ensaio pré-clínico aleatório em animais de experimentação por 35 dias. Os animais foram coelhos fêmeas (Oryctolagus cuniculus), da linhagem Nova Zelandia, submetidos à dieta ateroslcerótica e à angioplastia da artéria ilíaca externa direita. Os animais foram divididos em: Grupo A (n=10) coelhos tratados com a Allium sativum (800 μg/kg/dia), em doses diárias, por via oral. Grupo C (n=10): coelhos tratados com Cilostazol em doses diárias de 50 mg/dia, por via oral. Grupo S (n= 10) coelhos tratados com 10 mL de soro fisiológico 0,9%, por via oral, que foi nosso controle negativo. A variável primária foi a diferença de frequência da média de hiperplasia miointimal. Variáveis secundárias: a média de espessura da placa na parede arterial. Dados complementares: a frequência isquemia do membro, a frequência de perda do membro, a frequência de hematoma ou equimose, a frequência de infecção, a frequência de sangramento, a frequência de morte do animal e a média dos níveis lipídicos. O tamanho da amostra foi arbitrado em 30 coelhos. A análise estatística foi realizada com o teste ANOVA, Qui-quadrado e Tukey. Foi calculado o intervalo de confiança de 95% para cada ponto estimado. Os resultados foram: grupo S teve um índice médio de hiperplasia de 35,74% IC de 95% (31,76% a 39,71%); grupo C teve um índice médio de hiperplasia de 16,21% IC de 95% (13,36% a 19,05%); grupo A teve um índice médio de hiperplasia de 21,12% IC de 95% (17,26% a 25,01%); com P < 0,0001. Sendo assim, o Allium sativum tem a mesma eficácia na inibição da hiperplasia miointimal comparada aos tratados com Cilostazol