INTRODUÇÃO: A gordura visceral abdominal tem sido associada com os fatores de risco cardiovasculares e com a doença arterial coronária (DAC). A maior parte dos estudos delineados para avaliar o risco atribuído à distribuição da gordura corporal utilizaram as medidas antropométricas para estimar a gordura visceral. Entretanto, quando comparada com as medidas antropométricas tradicionais (circunferência do quadril e relação das medidas da cintura e quadril), a gordura visceral avaliada pela tomografia computadorizada (TC) foi mais intensamente associada aos fatores de risco para DAC. A angiografia por TC com múltiplos detectores é um método diagnóstico em ascensão, permitindo a detecção de DAC obstrutiva e não obstrutiva, acrescentando informação para a estratificação de risco cardiovascular. O objetivo desse estudo foi avaliar a associação entre DAC e as medidas de adiposidade por métodos clínicos e tomográficos. MÉTODOS: Nós avaliamos prospectivamente 125 indivíduos consecutivos (57% eram homens, idade média de 56 ± 12 anos) referenciados para realizar angiografia coronária por TC. As variáveis clínicas e laboratoriais foram determinadas e tomografias cardíacas e abdominais foram realizadas em um tomógrafo com 64 fileiras de detectores. A DAC foi definida pela presença de qualquer placa coronária, calcificada ou não, identificada pela angiografia por TC. As artérias coronárias foram classificadas de acordo com a presença ou não de estenoses significativas (obstrução do diâmetro luminal 50%). As calcificações coronárias foram determinadas pelo escore de cálcio. As medidas de gordura visceral e subcutâneas foram realizadas em diferentes níveis do espaço intervertebral. RESULTADOS: A angiografia por TC detectou DAC em 70 participantes (56%) e nenhuma associação foi encontrada com as medidas antropométricas usuais (circunferências de cintura e quadril e índice de massa corpórea). Entretanto, as medidas das áreas de gordura visceral abdominal (GVA) foram significativamente associadas ao diagnóstico de DAC. As médias das áreas de GVA no espaço intervertebral L1-T12 (GVA L1-T12) e L4-L5 (GVA L4-L5) foram 151,2 cm2 e 167,2 cm2, respectivamente. Valores de GVA L1-T12 145 cm2 apresentaram odds ratio de 2,85 (1,3 6,26, IC95%) para o diagnóstico de DAC e a GVA L4-L5 150 cm2 apresentou odds ratio de 2,87 (1,31 6,3, IC 95%) para DAC. As medidas de adiposidade não mostraram associação com o grau de estenose coronária, nem com a presença de calcificações coronárias identificadas pelo escore de cálcio. A análise multivariada determinou a idade e a GVAL1-T12 como as únicas variáveis independentemente associadas ao diagnóstico de DAC. CONCLUSÃO: A gordura visceral avaliada pela TC é um marcador independente de DAC diagnosticada pela angiografia coronária por TC. A avaliação da gordura visceral pela TC em diferentes sítios abdominais foi fortemente associada à DAC, e não se associou às tradicionais variáveis antropométricas e clínicas utilizadas para estimar o risco cardiovascular. A utilização das medidas de adiposidade pela TC na prática clínica pode agregar valor à estratificação de risco da DAC / INTRODUCTION: Visceral abdominal fat has been associated with cardiovascular risk factors and coronary artery disease (CAD). Visceral fat is frequently estimated using anthropometric measurements, but computed tomography (CT) studies have shown stronger association with CAD risk than anthropometric variables (waist circumference, waist-to-hip ratio). CT angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk stratification. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. METHODS: We prospectively evaluated 125 consecutive subjects (57% men, age 56.0 ± 12 years) referred to perform CT angiography. Clinical and laboratory data were determined. Cardiac CT and abdominal CT were performed in a 64- slice scanner. CAD was defined as the presence of any plaque detected by CT angiography and stenosis were graded as significant (greater than 50% of luminal narrowing) or nonsiginificant (less than 50%). The presence of coronary calcification was determined by calcium score. Visceral and subcutaneous adiposity measurements were determined at different intervertebral levels. RESULTS: CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements. Nevertheless CT visceral fat area (VFA) was significantly associated to CAD. The mean VFA at the intervertebral locations T12-L1 (VFA L1-T12) and L4-L5 (VFA L4-L5) were 151.2 cm2 and 167.2 cm2, respectively. VFA L1-T12 values 145 cm2 had an odds ratio of 2.85 (95% CI - 1.30 6.26) to CAD and VFA L4-L5 150 cm2 had a 2.87-fold (95% CI - 1.31-6.30) CAD risk. Adiposity measurement was not related to stenosis severity and neither to the presence of coronary calcification. The multivariate analysis determined age and VFA L1-T12 as the only independent variables associated to CAD. CONCLUSION: Visceral fat as assessed by CT angiography is an independent marker of CAD. VFA in different abdominal sites was strongly related to CAD but this relation was not found using anthropometric measurements and clinical variables. The use of these CT adiposity measurements in the clinical practice may improve the risk stratification to CAD

From this series of studies, we conclude that microalbuminuria may represent a novel risk factor in SLE, and lupus patients are more susceptible to endothelial dysfunction caused by hyperhomocysteinemia. The use of antimalarial agents is beneficial for lupus patients with active disease on corticosteroid, and antioxidant vitamins are useful in lowering the oxidative stress markers but do not affect the endothelial function. The results highlight the importance of targeting the known modifiable risk factors in order to prevent premature atherosclerosis in SLE patients. / My first step was to elucidate the prevalence and metabolic abnormalities in SLE patients with microalbuminuria. Twenty percent of patients were found to have microalbuminuria, which was associated with higher mean arterial pressure, total plasma antioxidant and homocysteine levels. / Next, we recruited 12 SLE patients and 15 controls and gave them oral methionine loading to achieve acute hyperhomocysteinemia. After oral methionine loading, von Willebrand factor (vWF) levels increased significantly in both groups. The increase in vWF was apparently more pronounced in SLE (20%) compared to controls (8%). Fibrinogen binding to platelets increased significantly only in SLE patients. / Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause which can affect any organs. Studies have reported an increased prevalence of cardiovascular disease (CVD) in these patients. We performed a series of studies to elucidate the interaction between microalbuminuria, dyslipidaemia, hyperhomocysteinemia, oxidative stress and immune dysregulation from the underlying disease in order to understand the accelerated atherosclerotic process in SLE. / We then evaluated the effects of long-term antioxidant vitamins. The plasma malondialdehyde level was significantly decreased after treatment in the vitamin group. Other oxidative stress markers and antioxidant levels and endothelial function remained unchanged in both groups. / We then proceeded to study the relative effect of antimalarial agents on fasting lipid fractions in patients with active SLE. Total cholesterol, very low-density lipoprotein cholesterol, and low density lipoprotein cholesterol levels were significantly lower in patients taking antimalarial agents, particularly for those patients taking concomitant prednisone. In the last study, we demonstrated that hydroxychloroquine had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. / Tam Lai Shan. / Adviser: Edmund K. Li. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1550. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 178-214). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

A ativação de Receptores de Hidrocarbonetos de Arila (AhR) é associada ao desenvolvimento de doenças cardiovasculares (DCV), dentre elas a aterogênese. Entretanto, não foi elucidado se a ativação do AhR por compostos/moléculas endógenas influenciaria o desenvolvimento de placas vulneráveis. Diante do exposto, o presente estudo testou a hipótese que a ativação do AhR mediada por compostos/moléculas endógenas contribui para o processo aterogênico e vulnerabilidade da placa aterosclerótica de camundongos nocautes para apoliproteína E (ApoE-/-). Nosso estudo mostrou que um dispositivo cilíndrico (cast), que promove estresse de cisalhamento baixo (ECB) e estresse de cisalhamento oscilatório (ECO), causa o desenvolvimento de placas ateroscleróticas com fenótipos vulnerável e estável de forma tempo dependente, em carótidas de camundongos ApoE-/- submetidos a dieta western. Regiões com ECB, apresentaram aumento na expressão de IL-1?, TNF-?, MMP-12 e do AhR, sugerindo que este receptor contribui com o processo inflamatório em placas vulneráveis, posto que ele regula a expressão gênica de mediadores pró-inflamatórios. O tratamento com CH223191 (antagonista AhR) diminuiu a vulnerabilidade da placa aterosclerótica, pois reduziu a quantidade de macrófagos, lipídeos, a geração de espécies reativas de oxigênio (EROs) e aumentou a quantidade de células de musculo liso (CML) em regiões com ECB. Além disso, o CH223191 reduziu a expressão de IL-1? em placas ateroscleróticas presentes no arco aórtico e a hipercolesterolemia dos camundongos ApoE-/-. Outrossim, nossos achados apontam que o CH223191 evita o prejuízo induzido por oxLDL na vasodilatação da artéria aorta de camundongos C57BL/6J. Em células endoteliais, a ativação do AhR mediada por oxLDL é responsável pela produção de IL-1?, evento bloqueado pelo CH223191. Nossos achados destacam o AhR como alvo promissor na compreensão de DCV e possível alvo terapêutico na aterosclerose. / Aryl hydrocarbon receptor (AhR) activation is associated with the development of cardiovascular diseases, including atherosclerosis. However, it is unknown whether AhR activation by endogenous compounds/molecules plays a role in the development and vulnerability of the atherosclerotic plaque. We hypothesized that AhR activation by endogenous compounds/molecules promotes atherogenesis and contributes to the formation of vulnerable plaques in apolipoprotein E knockout mice (ApoE-/-). A shear stress modifier (cylindrical device referred to as cast) was placed in the carotid arteries of ApoE-/- mice, creating areas of lower shear stress (LSS) and oscillatory shear stress (OSS), and inducing the development of atherosclerotic vulnerable and stable plaques, respectively, in a time-dependent manner. LSS regions exhibited increased expression of IL-1?, TNF-?, MMP-12 and AhR. Considering that AhR activation leads to transcription of proinflammatory markers transcription, it is possible that AhR expression in LSS regions is associated with the inflammatory process. Treatment with an AhR antagonist (CH223191) reduced lipid and macrophage accumulation and increased the smooth muscle cell content in LSS regions. Additionally, CH223191 reduced IL-1? expression in atherosclerotic plaques in the aortic arch from hypercholesterolemic ApoE-/- mice. Furthermore, CH223191 prevented oxLDL-induced vascular dysfunction (reduced ACh vasodilation) in C57BL/6J. In endothelial cells, oxLDL induced IL-1? release by mechanisms dependent on AhR activation, an effect prevented by CH223191. Our findings point to AhR as a possible new therapeutic target in cardiovascular diseases, including atherosclerosis.

Background: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterised by autoantibody production and variable clinical features, ranging from mild to severe disease. Patients with SLE are at increased risk of developing accelerated atherosclerosis. Biomarkers have potential utility in SLE as markers of disease or predictors of future clinical events and mortality. Objective The aim of this thesis was to identify serological biomarkers predictive for erosive arthritis (EA), cardiovascular events (CVEs), mortality and subclinical atherosclerosis in SLE. Methods: In chapters 2 to 4, study subjects were SLE patients from Bath. Anti-cyclic citrullinated peptide antibodies (ACPA) and HLA-DR and -DQ were studied for markers of EA, and anticardiolipin (aCL) and lipoprotein profiles for markers of CVEs and mortality. In chapters 5 and 6, study subjects were women with SLE from Manchester. B-mode ultrasound scans of subjects' carotid arteries were performed at baseline and follow-up time-points to detect atherosclerotic plaque. Baseline IgG and IgM antiphospholipid (aPL) antibodies and CV risk factors were studied for markers of subclinical atherosclerosis. Clinical data collected for all studies included SLE features and auto-antibody profiles. Results: ACPA was identified as a marker of a SLE phenotype with EA - "rhupus". Patients with major erosive arthritis were HLA-DQB1*0302 carriers. Increased aCL GPL levels and total cholesterol : high density lipoprotein-C (TC : HDL-C) ratio were markers for future CVEs, and increased TC : HDL ratio, aCL GPL and lipoprotein(a) concentrations were markers for increased mortality. Lower HDL-C concentrations and anti-annexin A5 (anti-AnxA5) GPL were markers of carotid plaque progression. Conclusion: This thesis identified new markers for EA, subclinical atherosclerosis and future CVE and mortality risk in SLE. Strategies to incorporate these new CV markers into clinical CV risk assessments may assist in distinguishing the subset of SLE patients most at risk of developing accelerated atherosclerosis.

INTRODUCTION: The“vulnerable plaque" is defined as the“precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

Les pathologies cardiovasculaires sont le plus souvent l’aboutissement des processus liés à l’athérosclérose. Elles représentent la première cause de morbi-mortalité dans le monde et leur incidence s’accroit avec le vieillissement de la population et l’expansion de facteurs de risques comme le diabète ou l’obésité. La sténose valvulaire aortique (SVA) est la valvulopathie la plus fréquente dans les pays développés présentant de nombreux points communs avec l’athérosclérose vasculaire. En plus des facteurs de risque, les lésions valvulaires et les lésions vasculaires partagent des similitudes dans les processus physiopathologiques impliqués comme l’inflammation, la fibrose, l’angiogenèse et la calcification. Ce dernier processus apparait dans les stades avancés des pathologies liées à l’athérosclérose et joue un rôle critique via son implication dans la stabilité de la plaque ou l’épaississement des cuspides valvulaires aortiques. Les macrophages, cellules issues de la différenciation des monocytes infiltrés, jouent un rôle prépondérant dans ces lésions via les phénotypes classiques (M1) et alternatifs (M2). Néanmoins cette dichotomie ne reflète pas complètement la variété de leur plasticité et les différents phénotypes induits notamment par le microenvironnement des monocytes/macrophages (zones riches en lipides, zones riches en fer ou zones riches en calcification). Dans la valve aortique, les cellules interstitielles de valve (VIC) forment la population cellulaire la plus présente au sein de la valve aortique. Ces cellules jouent un rôle déterminant dans le maintien du tissu valvulaire, mais également dans les processus de calcification menant à la SVA. Dans un premier temps, cette thèse a pour but d’étudier la capacité des macrophages à former des ostéoclastes, cellules responsables de la dégradation de la matrice osseuse, au sein des plaques d’athérosclérose. Dans un second temps, ce travail se focalisera sur les processus de calcification de la valve aortique via l’étude du rôle de la leptine dans les calcifications valvulaires (étude a priori) puis dans une étude transcriptomique sans a priori de VIC issues de valve sténosées et non-sténosées. Nos résultats sur les macrophages montrent ex vivo que les cellules en bordure des calcifications vasculaires sont des macrophages alternatifs de type M2. In vitro, ces cellules sont incapables de se différencier en ostéoclastes et de résorber une matrice osseuse. Pour l’étude de l’effet de la leptine sur les VIC, nous montrons que la leptine sérique est plus élevée chez des patients présentant une SVA, nous confirmons que la leptine et son récepteur sont exprimés au sein des valves aortiques et que la leptine favorise la différenciation ostéoblastique des VIC de manière dépendante des voies Akt et ERK. Enfin, l’étude transcriptomique a permis de mettre en évidence une nouvelle voie métabolique dérégulée dans les VIC. Cette enzyme est sous exprimée dans les VIC issues de valves pathologiques et dans les zones calcifiées des valves aortiques sténosées. Par ailleurs, le traitement des VIC par le produit de cette enzyme en milieu procalcifiant inhibe la calcification. Cette thèse met en avant de nouveaux indices sur les processus de calcification observés dans les plaques d’athérosclérose et les valves aortiques sténosées. Ces résultats décrivent l’impossibilité des M2 à former des ostéoclastes capables de résorber les calcifications. Il sera intéressant d’étudier le phénotype des macrophages en bordure des calcifications des valves aortiques sténosées. D’autre part, il sera intéressant d’étudier l’origine de la leptine dans la valve et son mécanisme d’action sur les VIC. Enfin, ce travail a mis à jour une nouvelle voie métabolique, impliquée dans le développement des calcifications valvulaires, qui pourrait constituer une voie thérapeutique innovante dans le traitement médicamenteux de la SVA. / Cardiovascular diseases (CVD) are the most often outcome of atherosclerosis processes. CVD are the first leading cause of death rate with an increasing incidence due to ageing populations and expansion of risk factors such as diabetes mellitus or obesity. Aortic valve stenosis (AVS) is the most frequent valvulopathy in developed countries sharing common points with vascular atherosclerosis. More than only risk factors, valvular and vascular lesions share common pathophysiological processes implicated in the development of the disease such as inflammation, fibrosis, angiogenesis and calcification. This last process appears in late stages of atherosclerosis diseases and play critical roles via implication in plaque stability or thickening of the aortic valve. Macrophages are cells deriving from infiltrated monocytes, playing an important role in the inflammatory state of lesions via classical (M1) or alternative phenotypes (M2) phenotypes. Nevertheless, this dichotomy does not reflect completely the variety of their plasticity and different phenotypes induced by the microenvironment of monocytes/macrophages (lipid riche zone, iron riche zone or calcium rich zone). In the aortic valve, valvular interstitial cells (VIC) are the most prominent cell type found in the aortic valve. These cells play a major role not only in the valve tissue homeostasis but also in the calcification processes leading to AVS. In a first part, the aim of this thesis is to elucidate the ability of macrophages to differentiate into osteoclasts, cell type responsible for bone matrix remodeling, inside atherosclerosis plaques. In a second part, this work will focus on the calcification processes occurring in the aortic valve via the study of the role of leptin in valvular calcification (association study) and then in a transcriptomic analysis of VIC isolated from calcified versus non calcified aortic valves (genome-wide expression study). Our results about macrophages show that ex vivo cell surrounding vascular calcification are alternative M2 macrophages. In vitro, these cells are no able to differentiate into true osteoclasts nor to resorb calcium deposits. Concerning the role of leptin on VIC, the results show that serum leptin is higher in patients with AVS, leptin and its receptors are expressed in the aortic valves and leptin enhances the osteoblast différenciation of VIC in an Akt and ERK dependant manner. Finally, the transcriptomic analysis allowed to highlight a new pathway deregulated in VIC. This enzyme is underexpressed in VIC isolated from calcified aortic valves and in the calcified zonesAbstract4of stenosed aortic valves. Otherwise, treating VIC with the product of this enzyme in a procalcifying medium inhibits calcification processes.This thesis highlights new insights into the calcification processes occurring in atherosclerosis lesions and calcified aortic valves. These results describe that M2 macrophages cannot differentiate into osteoclasts and reverse calcification formation inside atherosclerosis plaques. In parallel, it would be interesting to study the macrophages phenotypes surrounding calcium deposits in stenosed aortic valves. Then, it will be interesting to decipher the origin of leptin and its precise mechanism of action on VIC. Finally this work points out a new metabolic pathway implicated in the development of valvular calcification which could be a medical treatment of SVA.

Made available in DSpace on 2017-07-24T19:22:07Z (GMT). No. of bitstreams: 1 Chigueyuki Jitumori.pdf: 1740960 bytes, checksum: 9b32a5e7e1e0ef0d5aea1b277aaca545 (MD5) Previous issue date: 2008-02-25 / In the last years, a great amount of information suggested a possible relationship between periodontal disease and cardiovascular disease. Several scientific works showed a significant association between periodontal parameters and cardiovascular problems. The aim of this research went evaluate to oral health and the periodontal disease in humans verifiying if these conditions potentially could be correlated as possible risk factors for coronary artherosclerotic disease. Eighty patients were submitted the coronary angiography and divided in two groups: patients with coronary artherosclerotic disease (n=59) and patients without coronary artherosclerotic disease (n=21). The analyzed variables were age, gender, smoking, alcoholic using, family history of coronary disease, hypertension, diabetes, total cholesterol, LDL, HDL, triglicerides and obesity; reactive C protein, CK, CKMB, ureia, creatinin and number of erythrocytes, leucocytes and lymphocytes. The periodontal exam and of the condition of health and oral hygiene consisted of the following parameters: dental loss, tongue biofilm presence, number of periodontal pockets with clinical depth ³5mm; number of sites with loss of clinical insert ³6mm; gingival index, plaque index, number of patients and sites with exsudate. In the collected exsudates of periodontal pockets were accomplished microbiologic tests and Streptococcus of the group viridans alpha hemolyse and negative catalase were isolated in 43.75% of the samples. The results showed that the cholesterol levels increase was a tendency in the patients with and without coronary artherosclerotic disease with periodontal disease, coming significantly different when compared with the patients without artherosclerotic disease and without periodontal disease (p=0.0389) showing a relationship between periodontal disease and lipid metabolism. The parameters of oral hygiene (p=0.0237) and periodontal condition presented values significantly different when compared the groups (p<0.0001), presenting a difference among the proportions =0.2519 with 95% of the confidence interval of the difference = 0.058 to 0.445 and Odds Ratio=3.913. Suggesting that patients with periodontal disease have 4x larger probability approximately of having coronary problems (p=0.0125). / Nos últimos anos, uma grande quantidade de informações sugeriu uma possível relação entre doença periodontal e doença cardiovascular. Diversos trabalhos científicos mostraram uma associação significativa entre parâmetros periodontais e problemas cardiovasculares. O objetivo desta pesquisa foi avaliar a saúde bucal e o grau de omprometimento de doença periodontal em humanos verificando se potencialmente estas condições poderiam estar correlacionadas como possíveis fatores de risco para doença aterosclerótica coronariana. Oitenta pacientes foram submetidos a cinecoronariografia e divididos em dois grupos: pacientes com doença aterosclerótica coronariana (n=59) e pacientes sem doença aterosclerótica coronariana (n=21). As variáveis analisadas foram idade, sexo, tabagismo, etilismo, história familiar de doença coronariana, hipertensão arterial sistêmica, diabetes, colesterol total, LDL, HDL, triglicerídeos e obesidade; proteína C reativa, CK, CKMB, uréia, creatinina e contagem de eritrócitos, leucócitos e linfócitos. O exame periodontal e da condição de saúde e higiene oral consistiu nos seguintes parâmetros: perda dentária, presença de saburra, número de bolsas periodontais com profundidade clínica de sondagem ³ 5 mm; número de sítios com perda de inserção clínica 6 mm; índice gengival, índice de placa, número de pacientes e sítios com exsudato. Nos exsudatos coletados de bolsas periodontais foram realizados testes microbiológicos sendo que Streptococcus do grupo viridans alfa hemólise e catalase negativa foram isolados em 43.75% das amostras. Os resultados mostraram que o aumento dos níveis de colesterol foi uma tendência nos pacientes com e sem lesão aterosclerótica coronariana com doença periodontal, apresentando-se significativamente diferente quando comparado com os pacientes sem doença aterosclerótica e sem doença periodontal (p=0.0389) demonstrando uma relação entre doença periodontal e metabolismo lipídico. Os parâmetros de higiene oral (p=0.0237) e periodontais apresentaram valores significativamente diferentes quando comparados os grupos (p<0.0001), apresentando uma diferença entre as proporções =0.2519 com 95% do intervalo de confiança da diferença= 0.058 a 0.445 e Odds Ratio=3.913. Há o direcionamento conclusivo que pacientes com doença periodontal têm aproximadamente 4x maior probabilidade de ter problemas coronarianos (p=0.0125).

Submitted by Angela Maria de Oliveira (amolivei@uepg.br) on 2017-11-28T11:54:26Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Sandra Mara.pdf: 3331511 bytes, checksum: 1407ac27be63de1ae2c056443112849e (MD5) / Made available in DSpace on 2017-11-28T11:54:26Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Sandra Mara.pdf: 3331511 bytes, checksum: 1407ac27be63de1ae2c056443112849e (MD5) Previous issue date: 2015-03-12 / As doenças periodontais (DP) são condições infectoinflamatórias multifatoriais, que tem no biofilme dental sua etiologia primária, atinge mais de 70% da população mundial e podem influenciar na saúde geral do organismo. Outra doença inflamatória com alto índice de incidência e que se tornou um problema de saúde publica é a aterosclerose. Autores sugerem que a exposição sistêmica a infecções pode resultar na liberação de citocinas inflamatórias, que alteram o metabolismo lipídico, promove a hiperlipidemia, a hiperglicemia e a oxidação de lipídeos; agindo como fator de risco para as doenças cardiovasculares (DCV). Neste estudo foram analisados índices dos componentes sanguíneos; realizando uma análise comparativa dos dados obtidos por meio de exames laboratoriais e análise plasmática de LDL oxidado. Este estudo contou com 60 pacientes voluntários. Sendo que, 30 pacientes com história prévia de DCV, foram provenientes do Consórcio Intermunicipal de Saúde (CIS) 5ª Regional de Saúde do Centro-Oeste do Paraná; todos em tratamento. E 30 sem DCV foram provenientes da clínica odontológica S.M.M. Foram divididos em 4 grupos. Grupo SS 15 pacientes sem DP e sem DCV (controle). Grupo CC 15 pacientes com DP e com DCV. Grupo CS 15 pacientes com DP e sem DCV. Grupo SC 15 pacientes sem DP e com DCV. Foi considerado p<0,05. Não foram verificadas diferenças significativas para índice de leucócitos, plaquetas, HDL, triglicerídeos e na quantificação de colesterol oxidado entre os grupos. O grupo CC apresentou o menor índice de colesterol total com diferença significativa com o grupo CS p=0,0247. Para níveis de LDL o menor índice foi apresentado pelo grupo CC com diferenças significativas com os grupos CS p=0,0147 e SC p=0,0359. Também foram verificadas diferenças significativas no índice de glicose onde o grupo CC apresentou o maior índice entre os grupos com diferenças significativas com os grupos CS p=0,0259 e SS p=0,0043. / Periodontal diseases are chronic conditions infectius inflammatory, multifactorial, which has the biofilm its primary etiology, affects 70% of the population and may influence the overall health of the body. Another inflammatory disease with a high incidence rate and that has become a public health problem is atherosclerosis. Authors suggest that systemic exposure to infections may result in the release of inflammatory cytokines, which alter lipid metabolism, promotes hyperlipidemia, hyperglycemia and lipid oxidation; acting as a risk factor for cardiovascular disease (CVD). This study analyzed levels of blood components; conducting a comparative analysis of data obtained through laboratory tests and plasma analysis of oxidized LDL. This study included 60 volunteer patients. And, 30 patients with a history of CVD were from the Intermunicipal Consortium of Health (CIS) 5th Regional Health Center West of Paraná; all in treatment. And 30 without CVD were from the dental clinic SMM They were divided into 4 groups. Group SS 15 patients without PD and without CVD (control). Group CC 15 patients with PD and CVD. Group CS 15 PD patients without CVD. Group SC 15 patients without PD and CVD. It was considered p <0.05. No significant differences were observed for leukocyte, platelets, HDL, triglycerides index and quantitation of oxidized cholesterol between groups. The CC group showed the lowest total cholesterol index with a significant difference with the CS group p = 0.0247. For LDL levels the lowest index was presented by the CC group with significant differences with CS groups p = 0.0147 and SC p = 0.0359. Significant differences were also found in the glucose index where the CC group had the highest rate among the groups with significant differences with CS p = 0.0259 and p SS groups = 0.0043.

Hoje em dia existe um consenso de que a prevenção e o tratamento de doenças periodontais são importantes na redução de mortalidade e morbidade associadas à doença cardíaca, e uma correlação entre aterosclerose e doença periodontal ainda é desconhecida. Neste estudo, a presença de Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Campylobacter rectus e Enterococcus faecalis em placas de ateroma de artérias coronárias foram detectadas. Trinta pacientes programados para endarterectomia, 28 pacientes com periodontite crônica e 2 sem doença periodontal foram incluídos no estudo. DNA bacteriano foram extraídos dos ateromas e a presença de bactérias periodontais foram detectadas através da reação em cadeia da polimerase. DNA bacteriano periodontal foi encontrado em 28 amostras de ateroma de pacientes periodontais: P. gingivalis em 14 (50%); P. nigrescens em 4 (14,3%), P. intermedia em 3 (10,7%); E. faecalis em 3 (10,7%), T. forsythia em 2 (7,1%); A. actinomycetemcomitans em 2 (7,1%); C. rectus em 2 (7,1%); T. denticola em 1 (3,6%); e P. endodontalis em 1 (3,6%). Fusobacterium nucleatum não foi encontrado em nenhuma das amostras analisadas. Em duas amostras de ateroma de pacientes sem doença periodontal, P. gingivalis e E. faecalis foram observadas em uma amostra e P. intermedia em ambas as amostras. Nossos resultados sugerem que a presença de P. gingivalis em ateroma de artérias coronárias pode apresentar um envolvimento com aterosclerose e parecendo ser um microrganismo da relação aterosclerose e periodontite crônica. / Nowadays there is a consensus that prevention and treatment of periodontal diseases are important in the reduction of mortality and morbidity associated to cardiovascular diseases, and a correlation between atherosclerosis and periodontal disease is still unclear. In this study, the presence of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Campylobacter rectus and Enterococcus faecalis in atheroma plaques from coronary arteries was determined. Thirty patients scheduled for endarterectomy, 28 patients with chronic periodontitis and 2 without periodontal diseases were included in this study. Bacterial DNA was extracted from atheroma and periodontal bacteria detection was done by polymerase chain reaction. Periodontal bacterial DNA was found in 28 atheroma samples from periodontal patients: P. gingivalis in 14 (50%); P. nigrescens in 4 (14.3%); P. intermedia in 3 (10.7%); E. faecalis in 3 (10.7%), T. forsythia in 2 (7.1%); A. actinomycetemcomitans in 2 (7.1%); C. rectus in 2 (7.1%); T. denticola in 1 (3.6%); and P. endodontalis in 1 (3.6%) samples. Fusobacterium nucleatum was not detected in any atheroma analyzed. In two atheroma samples from patients without periodontal disease, P. gingivalis and E. faecalis were observed in one sample and P. intermedia in both samples. Our results suggest that the presence of P. gingivalis in atheroma from coronary arteries may be involved in atherosclerosis, and it appears to be a relationship microorganism atherosclerosis and chronic periodontitis.

Existe a hipótese, dentro da medicina periodontal, de uma possível relação entre doença periodontal e doenças cardíacas. Talvez a doença periodontal possa agir como um fator desencadeante para o desenvolvimento da doença cardiovascular. Vinte e oito pacientes portadores de aterosclerose e periodontite crônica, submetidos à intervenção cirúrgica de revascularização cardíaca e endarterectomia coronariana, participaram do estudo, cujo objetivo foi avaliar nas placas de ateroma de artérias coronárias a presença dos periodontopatógenos do complexo vermelho: Porphyromonas gingivalis, Tannerella forsythia e Treponema denticola. O DNA genômico foi extraídos das amostras de ateromas e se constatou a presença das bactérias através da reação em cadeia da polimerase (PCR). Detectou-se nas 28 amostras de ateroma: P. gingivalis em 50%, T. forsythia em 7,1% e T. denticola em 3,6% respectivamente. Estes resultados ajudam a defender a hipótese de que a doença periodontal pode ser um dos muitos fatores envolvidos com o desenvolvimento da doença cardiovascular, sendo mais um motivo para ser precocemente diagnosticada, prevenida e tratada. / In the field of periodontal medicine there is the hypothesis of a possible connection between periodontal diseases and heart diseases. Maybe the periodontal disease may work as a triggering factor in the development of periodontal of cardiovascular diseases. Twenty-eight patients of atherosclerosis and cronical periodontitis patients were subjected to surgical intervention for cardiac revascularization and coronary endarterectomy, have made part of the study, whose objective was to evaluate the presence of periodontopathogens of the red complex in the atheroma platelets: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Genomic DNA was extracted from atheroma samples, and the presence of bacteria was stated through polymerase chain reaction (PCR). In the 28 samples of atheroma were detected: P. gingivalis at 50%, T. forsythia at 7.1% and T. denticola at 3.6% respectively. These results help to sponsor the hypothesis that the periodontal disease can be one of several factors involved in the development of cardiovascular disease, being this another reason for its early diagnosis, prevention and treatment.