Introdução: A obesidade é um problema de saúde pública, de etiologia multifatorial, relacionada à incidência de comorbidades, como as doenças cardiovasculares - causa número um de mortes, globalmente. Contudo, os tratamentos para reverter essa condição não surtem efeito em longo prazo, fazendo com que novas intervenções para seu tratamento sejam utilizadas, como a abordagem Health at Every Size® (HAES®), que ainda mostra resultados inconclusivos quanto à melhora no perfil lipídico relacionado às doenças cardiovasculares. Objetivo: Analisar os efeitos de uma nova intervenção interdisciplinar baseada na abordagem HAES®, sobre o perfil lipídico relacionado às doenças cardiovasculares em mulheres obesas. Métodos: Estudo quantitativo, baseado em ensaio clínico randomizado controlado com duração de sete meses. Noventa e sete participantes foram recrutadas, após aprovação nos critérios de inclusão e exclusão da amostra, e foram aleatoriamente dividas nos grupos \"Intervenção\" ou \"Controle\", cujas atividades conduzidas tiveram os princípios da abordagem HAES® como norteadores. Participantes do grupo \"Intervenção\" realizaram cinco oficinas filosóficas, aconselhamento nutricional quinzenalmente e atividade física três vezes por semana. Já as participantes do grupo \"Controle\" participaram bimestralmente de palestras relativas à filosofia, nutrição e atividade física. A coleta e análise foram realizadas antes e depois da intervenção para os seguintes parâmetros: triglicérides, colesterol total, colesterol não-HDL, colesterol-VLDL, colesterol-LDL e colesterol-HDL. Variáveis foram comparadas antes e depois da intervenção usando Teste T de Student. Resultados: Foram observadas reduções para colesterol total, colesterol LDL e colesterol NHDL em ambos os grupos. Já para colesterol VLDL e triglicerídeos, houve aumento nos níveis observados. Quanto ao colesterol HDL, o grupo \"Intervenção\" teve uma diminuição após o estudo, ao passo que o grupo \"Controle\" teve um aumento no mesmo. Contudo, para todas as variáveis observadas, não houveram diferenças estatisticamente significativas. Conclusão: a intervenção por si não foi suficientemente eficaz para provocar mudanças no perfil lipídico. / Introduction: Obesity is a public health problem, with multifactorial etiology, related to the incidence of comorbidities, such as cardiovascular diseases - the number-one cause of death globally. However, treatments to reverse this condition have no long-term effect, and new interventions to treat obesity are formulated, such as the Health at Every Size® (HAES®) approach, which still shows inconclusive results regarding the improvement in metabolic profile related to cardiovascular diseases. Objective: To analyze the effects of a new interdisciplinary intervention based on the HAES® approach on biochemical markers related to cardiovascular diseases in obese women. Methods: Prospective, quantitative study based on a randomized controlled clinical trial lasting seven months. Ninety-seven participants were recruited, after approval in the inclusion and exclusion criteria of the sample, and were randomly assembled into the \"Intervention\" or \"Control\" groups, whose activities had the principles of the HAES® approach as guides. Participants in the Intervention group held five philosophical workshops, nutritional counseling every two weeks and physical activity three times a week. The participants of the \"Control\" group participated bimonthly in lectures related to philosophy, nutrition and physical activity. Data collection and analysis were performed before and after the intervention for the following parameters: triglycerides, total cholesterol, non-HDL cholesterol, VLDL-cholesterol, LDL-cholesterol and HDL-cholesterol. Variables were compared before and after the intervention using Student\'s t-test. Results: Reductions were observed for total cholesterol, LDL cholesterol and NHDL-cholesterol in both groups. On the other hand, for VLDL-cholesterol and triglycerides, there was an increase in the levels observed. As for HDL-cholesterol, the \"Intervention\" group had a decrease after the study, whereas the \"Control\" group had an increase in the same. However, for all observed variables, there were no statistically significant differences. Conclusion: The intervention itself was not effective enough to cause changes in the lipid profile.

O aumento excessivo de peso corporal acompanhado do acúmulo de gordura visceral eleva o risco de morbidade por hipertensão, diabetes mellitus tipo 2 e doença cardiovascular (DCV). O estresse oxidativo e a inflamação desempenham papel etiológico nestas comorbidades. Neste contexto, os microRNA (miRNA) atuam na regulação pós-transcricional no intuito de manter a homeostase celular sob condições de estresse fisiológico. A expressão de miRNA pode ser modulada por nutrientes e compostos bioativos provenientes da alimentação, atuando sobre processos inflamatórios, reduzindo o risco e/ou atenuando a progressão das DCV. A castanha-do-brasil é a maior fonte alimentar de selênio, sendo considerada um alimento com potencial função antioxidante podendo ser utilizado em pacientes com elevado risco cardiovascular. Dessa forma, o objetivo do presente estudo foi avaliar a expressão de microRNA circulantes em mulheres com excesso de peso antes e após o consumo da castanha-do-brasil. Para isso, foram selecionadas 72 mulheres com excesso de peso que frequentam o serviço de endocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). As participantes foram distribuídas aleatoriamente em dois grupos: grupo intervenção (grupo Brazil Nut - BN), que consumiu uma unidade de castanha-do-brasil durante 60 dias, e grupo controle (CO), que não recebeu intervenção durante o mesmo período. Ao início e ao final da intervenção foram realizadas avaliações antropométricas e coleta de sangue. Foram incluídas no estudo 54 participantes: 29 do grupo BN e 25 do grupo CO. Nenhuma das variáveis antropométricas e bioquímicas apresentou variação significativa entre os grupos durante o período de intervenção. Conforme esperado, apenas o grupo BN apresentou um aumento significativo do selênio plasmático e eritrocitário durante o período de intervenção (> 200%; P<0,001). Foram avaliados 25 miRNA plasmáticos antes e após a intervenção. Dois miRNA (miR-454-3p e miR-584-5p) apresentaram aumento significativo (fold change maior que 2,2; P<0,05) após a ingestão de castanha-do-brasil. A análise dos seus possíveis alvos pelo software Ingenuity Pathway Analysis (IPA®, Qiagen) apontou que ambos estão relacionados com a via de ativação do VDR/RXR, podendo apresentar efeitos sobre a homeostase do cálcio, regulação do crescimento e função imune. O miR-454-3p apresentou, ainda, correlação positiva com a variação do selênio plasmático (r=0,432; P=0,005) e diversos miRNA apesentaram correlação significativa com parâmetros relacionados à síndrome metabólica e à resistência à insulina. Dessa forma, podemos concluir que o consumo da castanha-do-brasil por 60 dias é capaz de modular a expressão de miRNA circulantes em mulheres com excesso de peso, particularmente do miR-454-3p e do miR-584-5p, podendo estes serem utilizados como possíveis biomarcadores de ingestão e auxiliar, ainda, no entendimento dos mecanismos pelos quais o selênio exerce seu efeito na saúde dessa população. / Excessive body weight gain accompanied by visceral fat accumulation raises the morbidity risk due to hypertension, type 2 diabetes mellitus and cardiovascular disease (CVD). Oxidative stress and inflammation play etiological role in these comorbidities. In this context, microRNAs (miRNAs) act in post-transcriptional regulation in order to maintain cellular homeostasis under physiological stress. MicroRNAs expression can be modulated by nutrients and bioactive compounds from the diet, acting on inflammatory processes, reducing the risk and/or attenuating the progression of CVD. Brazil nut is the major food source of selenium, being considered a food with potential antioxidant function to be used in patients with high cardiovascular risk. Thus, the present study aimed to evaluate the expression of circulating miRNAs in overweight and obese women before and after Brazil nuts intake. Thus, we selected 72 overweight and obese women recruited at Division of Endocrinology and Metabolism from the Clinical Hospital (School of Medicine, University of São Paulo, São Paulo, Brazil). Participants were randomly assigned to two groups: intervention group (Brazil Nut - BN group), which consumed one Brazil nut for 60 days, and control group (CO), which received no intervention during the same period. At the baseline and at the end of the intervention were performed anthropometric assessments and blood collection. The study included 54 participants: 29 from the BN group and 25 from the CO group. None of the anthropometric and biochemical variables presented significant variation between the groups during the intervention period. As expected, only the BN group showed a significant increase in plasma and erythrocyte selenium during the intervention period (> 200%; P<0.001). We evaluated 25 circulating miRNAs before and after the intervention. Two miRNAs (miR-454-3p and miR-584-5p) presented a significant increase (fold change greater than 2.2; P <0.05) after Brazil nuts intake. The analysis of potential targets by the Ingenuity Pathway Analysis software (IPA®, Qiagen) indicated that both are related to the VDR/RXR activation pathway, and may have effects on calcium homeostasis, growth regulation and immune function. Furthermore, miR-454-3p presented a positive correlation with plasma selenium (r = 0.432, P = 0.005) and several miRNAs showed a significant correlation with parameters related to metabolic syndrome and insulin resistance. Thus, we conclude that Brazil nut inatke for 60 days is capable of modulating circulating miRNAs in overweight and obese women, particularly miR-454-3p and miR-584-5p, and these may be used as possible biomarkers of intake and help to understand the mechanisms by which selenium exerts its effect on health of this population.

Estudos recentes sugeriram associação entre doença periodontal e doenças cardiovasculares e respiratórias. O objetivo deste estudo foi investigar a presença de bactérias periodontopatogênicas em placas ateromatosas humanas. Foram incluídos no estudo 24 pacientes de ambos os sexos, 40-60 anos de idade, internados na UTI do Hospital Nossa Senhora da Conceição em Tubarão-SC com indicação para endarterectomia. Após a coleta das placas ateromatosas, procedeu-se a identificação de sete diferentes espécies bacterianas periodontopatógenos por meio da reação em cadeia da polimerase em tempo real (RT-PCR). Para realização da análise estatistica foi verificada a associação entre as duas variáveis qualitativas nominais (presença ou ausência de bácterias X tipo de bactérias) por meio do teste Qui-quadrado, com nível designificância de 5 %. Os resultados desse trabalho mostraram haver associação entre presença ou ausência de bactérias e dos diferentes tipos de bactérias nos ateromas analisados (p = 0001). Dos ateromas avaliados 75% apresentaram Porphyromonas gingivalis., 58,3% Treponema denticola., 37,5% apresentaram Fusobacteriumnucleatum., 33,3% Prevotella intermedia., 20,8% Agreggatibacter actinomycetencomitanse. 0,4% de Prevotella nigrescens. Esses achados permitem concluir que bactérias periodontopatogênicas apresentam a capacidade de invadir a parede das artérias, podendo ter papel significativo no desenvolvimento ou ruptura das placas ateroescleróticas. / Recent studies suggested an association between periodontal disease and cardiovascular and respiratory diseases. The aim of this study was to investigate the presence of periodontopathogens in human atherosclerotic plaque. It were included in this study 24 non-smoking patients, both genders, 40-60 years, admitted at intensive unit care with indication of endarterectomy. After collection of carotid samples containing the lesions, the identification of seven different bacterial species was performed by real time polymerase chain reaction (RT-PCR). For statistical analysis, the association between two nominal qualitative variables (presence or absence of bactérias vs. bacterial specieis) was verified by Chi-squared test, with a 5% significance level. The results obtained showed an association between the presence or absence and bacterial species found in atheroma (p= .0001). Among the atheroma examined, 75% showed the presence of Porphyromonas gingivalis, 58.3% showed Treponema denticola, 37.5% showed Fusobacteriumnucleatum, 33.3% showed Prevotella intermedia, 20.8% Agreggatibacter actinomycetencomitans and 0.4% Prevotella nigrescens. These findings suggest that periodontopatoghens are capable of invading artery wall and could play a significant role in the development or rupture of atherosclerotic lesions.

Objetivo: Avaliar os aspectos clínicos e nutricionais de mulheres na pósmenopausa com doença arterial coronária (DAC). Metodologia: Estudo transversal retrospectivo. Obtiveram-se dados do prontuário médico de 217 mulheres, na ocasião da primeira consulta no Ambulatório de Nutrição do InCor-HCFMUSP, referentes à idade, índice de massa corpórea, presença de diabetes melito (DM), hipertensão arterial sistêmica (HAS), uso de drogas hipolipemiantes, perfil lipêmico (colesterol e frações) e consumo alimentar habitual. Para os dados dietéticos utilizou-se impresso próprio. Resultados: A idade média observada foi 60,98 &#177; 9,23 anos com prevalência de obesidade de 56%. A presença de DM, HAS e uso de drogas hipolipemiantes foi observada em 46%, 80% e 73%, respectivamente. Quanto ao perfil lipêmico, 44% apresentavam altos níveis plasmáticos de colesterol. Em relação ao consumo alimentar, 59% consumiam gorduras acima do limite superior aceitável e 95% apresentavam consumo deficiente de fibras alimentares. Conclusões: As inadequações observadas podem refletir no surgimento de fatores de risco para DAC e, apesar de já ter desenvolvido a doença, esta população ainda cultiva os fatores que o levaram a ela. Faz-se necessária a ação multidisciplinar em Programas de Saúde da Mulher, abrangendo aspectos preventivos relacionados a DAC para, assim, melhorar a qualidade de vida nesta população. / Objective: To assess clinical and nutritional aspects of postmenopausal women with coronary arterial disease (CAD). Methodology: Retrospective cross-sectional study. It was taken data of the clinicai handbook of 217 women, in first interview at Heart Institute (InCor) - HCFMUSP. The variables studied were: age, body mass index, diagnoses to diabetes mellitus (DM), hypertension (Hy), using of lipid-Iowering drugs, blood lipids (cholesterol and fractions) and food intake. It was used a specific tool for dietary data. Results: The mean age was 60,98&#177;9,23 years old with high prevalence of obesity (56%). DM, Hy and using of lipid-lowering drugs were observed in 46%, 80% and 73%, respectively. About blood lipids, 44% presented high serum cholesterol levels. About food intake, 59% had intake fats up to acceptable superior limit and 95% presented low dietary fiber intake. Conclusions: This inadequates data can reflect in the sprouting of factors of risk for DAC and despite already has developed the illness this population still cultivates the factors that had taken it. It is necessary the action of a multidiscipline team in Health Programs for Women, to involve preventive aspects related to the DAC and to improve the quality of life of this population.

Introdução: A obesidade é um problema de saúde pública, de etiologia multifatorial, relacionada à incidência de comorbidades, como as doenças cardiovasculares - causa número um de mortes, globalmente. Contudo, os tratamentos para reverter essa condição não surtem efeito em longo prazo, fazendo com que novas intervenções para seu tratamento sejam utilizadas, como a abordagem Health at Every Size® (HAES®), que ainda mostra resultados inconclusivos quanto à melhora no perfil lipídico relacionado às doenças cardiovasculares. Objetivo: Analisar os efeitos de uma nova intervenção interdisciplinar baseada na abordagem HAES®, sobre o perfil lipídico relacionado às doenças cardiovasculares em mulheres obesas. Métodos: Estudo quantitativo, baseado em ensaio clínico randomizado controlado com duração de sete meses. Noventa e sete participantes foram recrutadas, após aprovação nos critérios de inclusão e exclusão da amostra, e foram aleatoriamente dividas nos grupos \"Intervenção\" ou \"Controle\", cujas atividades conduzidas tiveram os princípios da abordagem HAES® como norteadores. Participantes do grupo \"Intervenção\" realizaram cinco oficinas filosóficas, aconselhamento nutricional quinzenalmente e atividade física três vezes por semana. Já as participantes do grupo \"Controle\" participaram bimestralmente de palestras relativas à filosofia, nutrição e atividade física. A coleta e análise foram realizadas antes e depois da intervenção para os seguintes parâmetros: triglicérides, colesterol total, colesterol não-HDL, colesterol-VLDL, colesterol-LDL e colesterol-HDL. Variáveis foram comparadas antes e depois da intervenção usando Teste T de Student. Resultados: Foram observadas reduções para colesterol total, colesterol LDL e colesterol NHDL em ambos os grupos. Já para colesterol VLDL e triglicerídeos, houve aumento nos níveis observados. Quanto ao colesterol HDL, o grupo \"Intervenção\" teve uma diminuição após o estudo, ao passo que o grupo \"Controle\" teve um aumento no mesmo. Contudo, para todas as variáveis observadas, não houveram diferenças estatisticamente significativas. Conclusão: a intervenção por si não foi suficientemente eficaz para provocar mudanças no perfil lipídico. / Introduction: Obesity is a public health problem, with multifactorial etiology, related to the incidence of comorbidities, such as cardiovascular diseases - the number-one cause of death globally. However, treatments to reverse this condition have no long-term effect, and new interventions to treat obesity are formulated, such as the Health at Every Size® (HAES®) approach, which still shows inconclusive results regarding the improvement in metabolic profile related to cardiovascular diseases. Objective: To analyze the effects of a new interdisciplinary intervention based on the HAES® approach on biochemical markers related to cardiovascular diseases in obese women. Methods: Prospective, quantitative study based on a randomized controlled clinical trial lasting seven months. Ninety-seven participants were recruited, after approval in the inclusion and exclusion criteria of the sample, and were randomly assembled into the \"Intervention\" or \"Control\" groups, whose activities had the principles of the HAES® approach as guides. Participants in the Intervention group held five philosophical workshops, nutritional counseling every two weeks and physical activity three times a week. The participants of the \"Control\" group participated bimonthly in lectures related to philosophy, nutrition and physical activity. Data collection and analysis were performed before and after the intervention for the following parameters: triglycerides, total cholesterol, non-HDL cholesterol, VLDL-cholesterol, LDL-cholesterol and HDL-cholesterol. Variables were compared before and after the intervention using Student\'s t-test. Results: Reductions were observed for total cholesterol, LDL cholesterol and NHDL-cholesterol in both groups. On the other hand, for VLDL-cholesterol and triglycerides, there was an increase in the levels observed. As for HDL-cholesterol, the \"Intervention\" group had a decrease after the study, whereas the \"Control\" group had an increase in the same. However, for all observed variables, there were no statistically significant differences. Conclusion: The intervention itself was not effective enough to cause changes in the lipid profile.

Bakgrund: Kardiovaskulär sjukdom är vida spridd över världen. Många riskfaktorer för sjukdomen bör kontrolleras med hjälp av hälsopreventiva insatser och kompletteras med läkemedelsbehandling. Syfte: Syftet var att undersöka vilka preventiva insatser som studerats för patienter med vaskulära sjukdomar, och effekterna av dessa. Metod: Designen var en litteraturstudie. Tillvägagångssättet var att söka artiklar med randomiserad kontrollstudie (RCT) design. 20 artiklar inkluderades och kvalitetsgranskades enligt checklista för RCT, och kvalitetsbedömning av RCT. Artikelsökningen gjordes i universitetets databaser: Pubmed/Medline, SKOPUS och CINAHL. En artikelsyntes skapades med utgångspunkt från PICO-modellen, (Population, Intervention, Comparison, Outcome), där fokus blev att jämföra interventioner och dess eventuella effekter. Som teoretiskt ramverk används Antonovsky’s känsla av sammanhang (KASAM). Begreppen begriplighet, hanterbarhet och meningsfullhet diskuteras. Resultat: De vanligaste sätten att bedriva prevention var via utbildningsinsatser och/eller rådgivande insatser. Dessa kan vara i möte eller via distans. De vanligaste effektmåtten kunde delas in i kategorierna: laboratorieprover, antropometriska mått, levnadsvanor, blodtryckskontroll, förändringar i riskprofil och följsamhet, upplevd livskvalitet, med flera. Bäst effekt enligt denna studie hade prevention inriktad mot utfallsmåtten blodtryck, blodfetter, blodglukos, samt följsamhet rörande vård och läkemedel.  Slutsats: Utbildning och rådgivning var bra preventiva metoder i samband med intervention mot kardiovaskulär sjukdom eller risk för sådan sjukdom. Det gällde oavsett om det gällde primär- eller sekundärprevention. Interventionerna var oftast inriktade mot livsstil. Effekterna var heterogena och varierande. Resultatet visar att blodtrycksreglering och reglering av blodfetter och blodsocker nivåer är möjliga, framförallt om följsamheten ökar. / Background: Cardiovascular disease is widely spread throughout the world. Many risk factors for the disease should be controlled by means of health preventive measures and supplemented with drug treatment. Purpose: The purpose was to investigate which preventive measures were studied for patients with vascular diseases, and the effects of these. Methods: The design was a literature study. The approach was to search for articles with randomized control trial (RCT) design. 20 articles were included and quality checked according to checklist for RCT, and quality assessment of RCT. The article search was done in the university's databases: Pubmed/Medline, SKOPUS and CINAHL. An article synthesis was created from the PICO model, (Population, Intervention, Comparison, Outcome). There, focus was on comparing interventions and its possible effects. As theoretical framework, Antonovsky’s Sense of Coherence (SOC) was used. The concepts of comprehensibility, manageability and meaningfulness are discussed. Results: The most common ways of conducting prevention were through training initiatives and/or advisory initiatives. These can be in personal meetings or remotely. The most common measures of effectiveness could be divided into categories: laboratory samples, anthropometric measures, lifestyle habits, blood pressure control, changes in risk profile and compliance, perceived quality of life, and more. The best effect according to this study was prevention aimed at the outcome measures blood pressure, blood lipids, blood glucose, and adherence to care and medication. Conclusion: Education and counseling were good preventative methods in connection with intervention against cardiovascular disease or the risk of such disease. It applied irrespective of the use of primary or secondary prevention. The interventions were usually focused on lifestyle. The effects were heterogeneous and varied. The result shows that blood pressure regulation and regulation of blood lipids and blood sugar levels are possible, especially if compliance is increasing.

Vitamin D deficiency in patients with chronic kidney disease, measured by reduced serum concentrations of 25 hydroxy vitamin D, is highly prevalent and associated with both endothelial dysfunction and an increased risk of cardiovascular disease. Observational studies in chronic kidney disease have demonstrated that vitamin D therapy reduces the risk of cardiovascular disease. In patients with chronic kidney disease and concomitant vitamin D deficiency, the effect of vitamin D therapy on endothelial function, which is associated with cardiovascular disease, is poorly understood. The mechanism by which vitamin D affects endothelial function is unclear. Methods Presented in this thesis, two studies have addressed these issues: 1. A double blind, randomized controlled trial evaluating the effect of ergocalciferol compared to placebo on microcirculatory endothelial function in patients with non-dialysis chronic kidney disease and concomitant vitamin D deficiency 2. In vitro and in vivo experiments to determine the mechanistic effect of ergocalciferol on endothelial function in an experimental model of uraemia. Results In the clinical study, ergocalciferol increased vitamin D serum concentrations and improved microcirculatory endothelial function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Oxidative stress measured by skin autofluorescence for advanced glycation end products did not change in the ergocalciferol group but increased significantly in the placebo group. Ergocalciferol increased endothelial nitric oxide synthase expression and activity in cultured human endothelial cells and improved endothelial function in an in vivo model of mild uraemia. The findings from the in vivo and clinical studies occurred independently of changes in blood pressure, conduit artery function, serum calcium, phosphate and parathyroid hormone supporting in vitro findings that ergocalciferol acts directly on the endothelium. Conclusion Ergocalciferol improved endothelial function in both rodent and human subjects with chronic kidney disease. Experimental evidence suggests this effect occurs through an endothelium dependent mechanism involving changes in the upregulation and function of endothelial nitric oxide synthase.

Introduction. Fused Positron Emission Tomography and Computed Tomography (PET/CT) is an emerging investigative tool in cardiovascular disease that provides an imaging-based quantification of pathophysiological processes of interest. The purpose of this thesis was to study the application of PET to identify fundamental pathophysiological processes driving 3 forms of cardiovascular disease: aortic stenosis, myocardial infarction, and atherosclerosis. Methods. Aortic Stenosis. Patients with a spectrum of calcific aortic valve disease (n=121) who underwent PET-CT imaging for the identification of valvular calcification (18Ffluoride) and inflammation (18F-fluorodeoxyglucose, 18F-FDG) underwent serial imaging and clinical follow-up over 2 years. Baseline imaging findings were compared with echocardiographic and CT markers of disease progression and clinical outcome. Myocardial Infarction. Patients underwent PET-CT imaging with 18F-fluciclatide (a novel αvβ3-selective radiotracer highlighting active angiogenesis, inflammation and fibrosis) after ST-segment elevation MI (n=21), alongside stable patients with chronic total occlusion (CTO) of a major coronary vessel (n=7), and healthy volunteers (n=9). Myocardial radiotracer uptake was compared with clinical and cardiac magnetic resonance imaging (CMR) markers of infarction and remodeling. Atherosclerosis. Patients with a spectrum of atherosclerotic disease categorized as stable or unstable (recent MI) underwent PET/CT imaging with 18F-fluciclatide (n=46). Thoracic aortic 18F-fluciclatide uptake was compared with aortic atherosclerotic burden quantified by CT plaque thickness, plaque volume and calcium scoring. Histological validation. Tissue from the aortic valve, myocardium and carotid arteries of study subjects was acquired and examined ex vivo using histology and autoradiography. Results. Aortic Stenosis. Baseline valvular 18F-fluoride uptake correlated strongly with the rate of progression in AVC (r=0.80, p < 0.001) and with haemodynamic progression (mean aortic valve gradient r=0.32, p=0.001). It emerged as independently associated with clinical outcome after age and sex-adjustment (HR 1.55 [1.33-1.81], p < 0.001). 18F-FDG demonstrated moderate correlations with disease progression as assessed by CT (r=0.43, p=0.001) and echocardiography (18F-FDG r=0.30, p=0.001), and was associated with clinical outcomes independent of age and sex (HR 1.35 [1.16-1.58], p < 0.001). Valvular 18F-fluoride uptake correlated with immunohistochemical markers of calcification activity. There was no correlation between 18F-FDG uptake and inflammation. Myocardial Infarction. 18F-Fluciclatide binding was demonstrated in ex vivo peri-infarct myocardium and uptake was increased in vivo at sites of acute infarction compared to remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17 respectively, p < 0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p < 0.001). There was no 18F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with myocardial activity similar to healthy volunteers (TBRmean 0.71±0.06 vs. 0.70±0.03,p=0.83). 18F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index ≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p < 0.001), was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. Atherosclerosis. 18F-Fluciclatide vascular binding ex vivo co-localised with regions of increased αvβ3 integrin expression, and markers of inflammation and angiogenesis. 18F-Fluciclatide uptake in vivo correlated with measures of aortic atherosclerotic burden: plaque thickness (r=0.57, p=0.001), total plaque volume (r=0.56, p=0.001) and the CT aortic calcium score (r=0.37, p=0.01). Patients with recent MI had greater aortic 18F-fluciclatide uptake than those with stable disease (TBRmax 1.33 vs 1.21, p=0.01). Conclusions. In a range of cardiovascular diseases, PET-CT can provide insights into key pathophysiological processes, guide patient risk stratification and prognosis, and identify important biomarkers of disease activity that can be used for the development of future therapeutic interventions.

Cardiovascular disease (CVD) is a complex combination of multiple conditions. The majority of deaths within CVD include heart attacks and strokes caused by atherosclerotic disease. The pathophysiological process for atherosclerotic disease occurs within the endothelial lining of the vessels of the body. This prolonged process occurs when cholesterol deposits form irregularity in luminal flow resulting in decreased blood flow and ischaemia. This unstable cholesterol plaque can rupture resulting in clot formation and artery occlusion. Within this thesis I aim to show background to the relevant pathophysiology of ischaemic heart disease (IHD) with the main emphasis on acute myocardial infarction (AMI), the history of its therapy to current therapy. I will discuss the theorised role of stem cell therapy within animal models and previous clinical trials within regenerative medicine and AMI. I will describe and discuss the method and the results of the REGENERATE-AMI trial (Clintrial.gov: NCT00765453), which will include the safety and efficiency of the therapy, and the possible cytokine mechanism by which this therapy may exert it effect. Additionally I will describe the potential for assessing myocardial oedema using 3-slice T2-STIR short axis stack imaging post AMI compared to the conventional 10-slice T2-STIR technique to assess its feasibility and clinical similarity to assess its use as a tool in translational research.

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.