Atherosclerosis, one major cause of morbidity and mortality worldwide, is a complex and multifactorial disease that involves three mainly conditions: chronic inflammation, dyslipidemia and oxidative stress. Although statins are the first-line therapy for LDL cholesterol (LDL-C) lowering, the efficacy of cardiovascular events prevention is limited to 30-40%. This residual risk brought attention to the need of new therapies and clinical targets beyond LDL-C, such as inflammation and oxidative stress. Importantly, suboptimal treatment and/or statin discontinuation due to adverse effects have also been a very challenging clinical problem. Complementary diet therapy can be an effective and safe approach to support pharmacological treatment, especially when drugs alone are insufficient to attenuate risk factors and/or the recommended dose is not well tolerated. The aim of this study was to evaluate the effects of three bioactive components, namely omega-3 fatty acids, plant sterols and polyphenols, on markers of dyslipidemia, inflammation and oxidative stress in patients treated with statins. A randomized, crossover clinical study was carried out, with the participation of 53 subjects. At each intervention period, study participants received a packaged for the functional or control treatment. Functional treatment consisted of fish oil (1.7 g of EPA+DHA/day), chocolate containing plant sterols (2.2 g/day) and green tea (two tea sachets/day). Control treatment consisted of soy oil softgels, regular chocolate and anise tea. After 6 weeks of intervention, functional treatment reduced plasma LDL-C (-13.7% ± 3.7, p=0.002) and C-reactive protein (-35.5% ± 5.9, p=0.027). Plasma triacylglycerol (-15.68% ± 5.94, p=0.02) and MDA (-40.98% ± 6.74, p=0.04) were reduced in subgroups of patients (n=23) with baseline values above the median (93 mg/dL and 2.23 umol/L, respectively). Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its endogenous synthesis. After multivariate analysis, patients identified as \"good responders\" to supplementation (n=10) were recruited for a pilot protocol of statin dose reduction with complementary diet therapy. Responders received the functional treatment for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6 to 12. No difference was observed for plasma lipids and inflammation biomarkers, cholesterol efflux capacity or HDL particle number after statin dose reduction when compared to standard therapy. Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. This may be particularly helpful for the many patients with, and at risk for, CVD who cannot tolerate high-dose statin therapy. / A aterosclerose, uma importante causa mundial de morbidade e mortalidade, é uma doença complexa e multifatorial que envolve três principais condições: inflamação crônica, dislipidemia e estresse oxidativo. Embora as estatinas sejam fármacos de primeira linha para redução de LDL colesterol (LDL-C), sua eficácia na prevenção de eventos cardiovasculares é limitadada a 30-40%. Este risco cardiovascular residual evidencia a necessidade de novas terapias e marcadores clínicos que vão além do LDL-C, como inflamação e estresse oxidativo. Não obstante, tratamento subótimo e/ou interrupção do uso de estatinas devido à ocorrencia de efeitos adversos também é um grave obstáculo na clínica médica. Neste contexto, a terapia dietética complementar representa uma abordagem efetiva e segura para o suporte do tratamento farmacológico, especialmente quando as drogas são insuficientes para atenuar fatores de risco e/ou quando a dose recomendada não é bem tolerada. O objetivo do presente estudo foi avaliar o efeito de três compostos bioativos - ácidos graxos ômega 3, fitosteróis e polifenóis - sobre marcadores de inflamação, lipemia e estresse oxidativo em indivíduos tradados com estatinas. Foi realizado um estudo clínico randomizado, de delineamento crossover, com a participação de 53 voluntários. A cada período de intervenção, os participantes receberam um tratamento funcional ou controle. O tratamento funcional foi composto por cápsulas de óleo de peixe (1.7 g/dia de EPA+DHA), chocolate contendo fitosteróis (2.2 g/dia) e chá verde (dois sachês/dia). O tratamento controle foi composto por cápsulas de óleo de soja, chocolate sem adição de fitosteróis e chá de anis. Após 6 semanas de intervenção, o tratamento funcional reduziu a concentração plasmática de LDL-C (-13.7% ± 3.7, p=0.002) e proteína C-reativa (-35.5% ± 5.9, p=0.027). Triglicerídeos (- 15.68% ± 5.94, p=0.02) e malondialdeído (-40.98% ± 6.74, p=0.04) foram reduzidas apenas em subgrupos de indivíduos que apresentavam valores basais acima da mediana (93 mg/dL e 2.23 umol/L, respectivamente). A análise de latosterol e campesterol no plasma sugeriu que a intensidade da redução de LDL-C não foi influenciada pela síntese endógena de colesterol, mas sim pela taxa de absorção. Após análise multivariada dos resultados, pacientes identificados como \"good responders\" à suplementação (n=10) foram recrutados para um estudo piloto de redução da dosagem da estatina, aliado à terapia dietética complementar. Estes pacientes receberam o tratamento funcional por 12 semanas: durante as 6 primeiras semanas mantevese a dosagem de estatina, que em seguida foi reduzida em 50% das semanas 6 a 12. Não foram observadas diferenças para os marcadores plasmáticos de lipídeos, inflamação, capacidade de efluxo de colesterol ou número de partículas de HDL após a redução da dose de estatina, quando comparada à terapia convencional. Embora limitado pelo reduzido número de pacientes, o estudo demonstra o potencial para uma nova abordagem terapêutica, combinando reduzida dose de estatina com específicos compostos bioativos. Esta pode ser uma importante alternativa para muitos pacientes em risco cardiovascular e que são intolerantes à terapia com altas doses de estatina.

Effet de l’atorvastatine sur la dysfonction endothéliale des artères coronaires épicardiques associée à l’hypertrophie ventriculaire gauche dans un modèle porcin Forcillo J, Aubin MC, Horn A, Shi YF, Carrier M, Tardif JC, Perrault LP Introduction: L’atorvastatine par ses effets pléiotropiques pourrait limiter la dysfonction endothéliale associée au développement de l’HVG. Méthodologie : Un cerclage de l’aorte ascendante pendant 2 mois entraîne le développement d’HVG et les groupes ont été traités avec atorvastatine 40 ou 80 mg de 60 à 90 jours. L’HVG est confirmée par échographie. La réactivité vasculaire est évaluée en chambres d’organe, la fonction endothéliale par la quantification de la GMPc et des nitrites/nitrates plasmatiques. Le stress oxydant est mesuré par les niveaux d’ANG II et de la carbonylation des protéines. Résultats : Après 60 et 90 j de cerclage, l’HVG est observée chez tous ces groupes. Les courbes concentrations-réponse des anneaux des artères coronaires épicardiques des groupes traités avec l’atorvastatine 40 et 80 mg pour 30 et 60 jours n’ont démontré aucune amélioration des relaxations dépendantes de l’endothélium. Une exacerbation significative de la dysfonction endothéliale a été observée. Les niveaux vasculaires de GMPc sont significativement diminués dans le groupe sans cerclage traité 60 d et ceux d’ANG II sont fortement augmentés chez ce dernier groupe ainsi que le groupe traité avec 80 mg pour 30 jours par rapport aux contrôles. L’expression de la carbonylation des protéines est augmentée dans le groupe témoin traité avec atorvastatine 80 mg, reflétant une augmentation du stress oxydant. Conclusion : L’administration d’atorvastatine ne prévient pas le développement de l’HVG ni la dysfonction endothéliale dans notre modèle. Au contraire l’atorvastatine à haute dose a un effet toxique sur les artères coronaires épicardiques en augmentant la dysfonction endothéliale. / Effect of atorvastatin on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy in a porcine model. Forcillo J, Aubin MC, Horn A, Shi YF, Carrier M, Tardif JC, Perrault LP Background: Atorvastatin, through pleiotropic effects, may prevent or reverse the endothelial dysfunction associated with LVH. Methods: After performing a banding of the ascending aorta for 2 months leading to the development of LVH, groups have been treated with atorvastatin 40 or 80 mg for 60 and 90 day periods. LVH was evaluated by echocardiographic studies. Vascular reactivity studies were performed in organ chambers. In vitro endothelial function was evaluated by plasmatic nitrites/nitrates, the degradations products of nitric oxide, and cGMP quantification. To quantify and qualify oxidative stress, protein carbonyl and angiotensin II levels were assessed. Results: Following 60 and 90 days of aortic banding, the development of LVH was observed in these groups. Concentration-response curves from rings of epicardial coronary arteries of groups treated with atorvastatin 40 and 80 mg for 30 and 60 days showed a significant decrease of endothelium-dependent relaxations with worsening of the endothelial dysfunction. Levels of cGMP were significantly decreased in the 60 days treated sham group and levels of ANG II were increased in the latter and also in the 90 days banded groups treated with 80 mg for 30 days compared to controls. The expression of protein carbonyl increased in the sham group treated with atorvastatin 80 mg compatible with an increase in oxidative stress. Conclusion: The administration of atorvastatin does not limit the development of LVH nor the endothelial dysfunction in our model. On the opposite, atorvastatin at a high dose has a toxic effect on epicardial coronary arteries by exacerbating the endothelial dysfunction.

L’athérosclérose est une pathologie artérielle chronique évoluant sur plusieurs années ou dizaines d’années. Sa traduction clinique est variable, pouvant rester longtemps asymptomatique, ou induire des symptômes d’effort directement lié à la réduction du calibre de l’artère (angor, claudication des membres inférieurs). Malgré cette évolution en apparence lente et progressive, les manifestations cliniques aiguës de cette pathologie sont souvent de survenue brutale. La formation de thrombus en regard des lésions athéromateuses dites déstabilisées représente la composante physiopathologique la plus fréquemment rencontrée. Cette complication aigüe de la plaque athéromateuse est responsable d’événements cardio-vasculaires majeurs impactant la morbi-mortalité, représentés par les syndromes coronariens aigus, les accidents vasculaires cérébraux ischémiques, et les ischémies aigues de membre inférieur. Après une revue des connaissances actuelles sur la plaque athéromateuse, nous étudierons à l’aide d’un modèle animal d’athérosclérose, son évolution, ses caractéristiques morphologiques, et nous testerons l’impact d’un traitement au long cours par statine en prévention primaire sur les plaques athéromateuses et sur les composants de la paroi vasculaire. Puis, dans une approche clinique, nous nous intéresserons à la durée optimale du traitement par double antiagrégant plaquettaire instauré après un traitement par angioplastie percutanée de plaque athéromateuse. Dans un second temps, nous détaillerons l’évolution des pratiques d’angioplastie coronaire en analysant les facteurs ayant contribué à limiter l’utilisation des stents non actifs (dit nus) au cours des 10 dernières années. Enfin, nous étudierons les principaux facteurs restant associés à la survenue d’un accident vasculaire cérébral post angioplastie percutanée, correspondant à l’une des principales complications majeures de ces procédures. / Atherosclerosis is a chronic arterial disease that progresses over several years or decades. Its clinical translation is variable, and may remain asymptomatic for a long time, or induce symptoms of stress directly related to the reduction in size of the artery (angina, chronic limb ischemia). Despite this seemingly slow and progressive evolution, the acute clinical manifestations of this pathology often occur suddenly. Thrombus formation in regard to the “destabilized” atheromatous lesions is the most frequently physiopathological components. This acute complication of atheromatous plaque is responsible of major cardiovascular events impacting the morbi-mortality, mostly represented by acute coronary syndromes, ischemic strokes, and acute lower limb ischemia. After a review of current knowledge on atheromatous plaque, we will study using an animal model of atherosclerosis, its evolution, its morphological characteristics, and we will test the impact of a long-term statin treatment in primary prevention on atheromatous plaques and on vascular wall components. Then, in a clinical approach, we will look at the optimal duration of double platelet antiaggregant after angioplasty. In a second step, we will detail the evolution of coronary angioplasty practices by analyzing the main factors that have contributed to limiting the use of bare metal stent over the past 10 years. Finally, we will analyze the major factors still associated with the occurrence of a stroke after percutaneous angioplasty.

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2018-03-12T17:36:57Z No. of bitstreams: 1 PEDRO HENRIQUE RODRIGUES DE ALENCAR AZEVEDO.pdf: 15048741 bytes, checksum: a121d29e5dc4898c7b8e4a85def01e12 (MD5) / Made available in DSpace on 2018-03-12T17:36:57Z (GMT). No. of bitstreams: 1 PEDRO HENRIQUE RODRIGUES DE ALENCAR AZEVEDO.pdf: 15048741 bytes, checksum: a121d29e5dc4898c7b8e4a85def01e12 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As calicreínas teciduais humanas (KLKs) compreendem uma família de 15 enzimas serina proteases (KLKs 1-15) amplamente encontradas nos tecidos humanos. Em diversas patologias como a dermatite atópica, psoríase, síndrome de Netherton, câncer de ovário, mama e testículos, as KLKs encontram-se em concentrações elevadas. Por exemplo, as KLKs 5 e 7 estão mais abundantemente expressadas na pele, na qual estão envolvidas com o processo de descamação da mesma, e também presentes em alguns tipos de carcinomas. Dessa forma, as KLKs 5 e 7 são consideradas importantes alvos terapêuticos para o tratamento de doenças onde elas encontram-se superexpressadas, enfatizando a existência de somente um fármaco comercialmente disponível como inibidor de KLK. Nesse contexto, o trabalho descreve a síntese de 3 séries de compostos peptideomiméticos, incorporando o cerne estatina e diferentes resíduos de aminoácidos, planejados como candidatos a inibidores das enzimas serina proteases do KLKs 5 e 7. Os compostos finais foram obtidos utilizando uma rota sintética eficiente tendo como reação-chave a formação da ligação peptídica entre o cerne estatina e cloridratos de aminoésteres, previamente sintetizados. Os compostos sintetizados foram identificados por técnicas de Ressonância Magnética Nuclear, Infravermelho e Espectrometria de massas de alta resolução e os produtos finais serão avaliados em testes in vitro de inibição das enzimas KLKs / Human tissue kallikreins (KLKs) comprise a family of 15 serine protease enzymes (KLKs 1-15) widely found in human tissues. In several pathologies such as atopic dermatitis, psoriasis, Netherton syndrome, ovarian, breast and testis cancer, KLKs are in high concentrations. For example, KLKs 5 and 7 are more abundantly expressed in the skin, in which they are involved in the desquamation process, and also present in some types of carcinomas. Thus, KLKs 5 and 7 are considered important therapeutic targets for the treatment of diseases where they are over expressed, emphasizing the existence of only one commercially available drug as a KLK inhibitor. In this context, the work describes the synthesis of three series of peptideomimetic compounds incorporating the statin core and different amino acid residues, designed as candidates for inhibitors of the serine protease enzymes of KLKs 5 and 7. The final compounds were obtained using an efficient synthetic route based on the reaction of formation of the peptide bond between the statin core and previously synthesized amino acid hydrochlorides. The synthesized compounds were identified by Nuclear Magnetic Resonance, Infrared and High Resolution Mass Spectrometry techniques and the final products will be evaluated in in vitro inhibition assays of the KLKs enzymes

Atherosclerosis, one major cause of morbidity and mortality worldwide, is a complex and multifactorial disease that involves three mainly conditions: chronic inflammation, dyslipidemia and oxidative stress. Although statins are the first-line therapy for LDL cholesterol (LDL-C) lowering, the efficacy of cardiovascular events prevention is limited to 30-40%. This residual risk brought attention to the need of new therapies and clinical targets beyond LDL-C, such as inflammation and oxidative stress. Importantly, suboptimal treatment and/or statin discontinuation due to adverse effects have also been a very challenging clinical problem. Complementary diet therapy can be an effective and safe approach to support pharmacological treatment, especially when drugs alone are insufficient to attenuate risk factors and/or the recommended dose is not well tolerated. The aim of this study was to evaluate the effects of three bioactive components, namely omega-3 fatty acids, plant sterols and polyphenols, on markers of dyslipidemia, inflammation and oxidative stress in patients treated with statins. A randomized, crossover clinical study was carried out, with the participation of 53 subjects. At each intervention period, study participants received a packaged for the functional or control treatment. Functional treatment consisted of fish oil (1.7 g of EPA+DHA/day), chocolate containing plant sterols (2.2 g/day) and green tea (two tea sachets/day). Control treatment consisted of soy oil softgels, regular chocolate and anise tea. After 6 weeks of intervention, functional treatment reduced plasma LDL-C (-13.7% ± 3.7, p=0.002) and C-reactive protein (-35.5% ± 5.9, p=0.027). Plasma triacylglycerol (-15.68% ± 5.94, p=0.02) and MDA (-40.98% ± 6.74, p=0.04) were reduced in subgroups of patients (n=23) with baseline values above the median (93 mg/dL and 2.23 umol/L, respectively). Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its endogenous synthesis. After multivariate analysis, patients identified as \"good responders\" to supplementation (n=10) were recruited for a pilot protocol of statin dose reduction with complementary diet therapy. Responders received the functional treatment for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6 to 12. No difference was observed for plasma lipids and inflammation biomarkers, cholesterol efflux capacity or HDL particle number after statin dose reduction when compared to standard therapy. Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. This may be particularly helpful for the many patients with, and at risk for, CVD who cannot tolerate high-dose statin therapy. / A aterosclerose, uma importante causa mundial de morbidade e mortalidade, é uma doença complexa e multifatorial que envolve três principais condições: inflamação crônica, dislipidemia e estresse oxidativo. Embora as estatinas sejam fármacos de primeira linha para redução de LDL colesterol (LDL-C), sua eficácia na prevenção de eventos cardiovasculares é limitadada a 30-40%. Este risco cardiovascular residual evidencia a necessidade de novas terapias e marcadores clínicos que vão além do LDL-C, como inflamação e estresse oxidativo. Não obstante, tratamento subótimo e/ou interrupção do uso de estatinas devido à ocorrencia de efeitos adversos também é um grave obstáculo na clínica médica. Neste contexto, a terapia dietética complementar representa uma abordagem efetiva e segura para o suporte do tratamento farmacológico, especialmente quando as drogas são insuficientes para atenuar fatores de risco e/ou quando a dose recomendada não é bem tolerada. O objetivo do presente estudo foi avaliar o efeito de três compostos bioativos - ácidos graxos ômega 3, fitosteróis e polifenóis - sobre marcadores de inflamação, lipemia e estresse oxidativo em indivíduos tradados com estatinas. Foi realizado um estudo clínico randomizado, de delineamento crossover, com a participação de 53 voluntários. A cada período de intervenção, os participantes receberam um tratamento funcional ou controle. O tratamento funcional foi composto por cápsulas de óleo de peixe (1.7 g/dia de EPA+DHA), chocolate contendo fitosteróis (2.2 g/dia) e chá verde (dois sachês/dia). O tratamento controle foi composto por cápsulas de óleo de soja, chocolate sem adição de fitosteróis e chá de anis. Após 6 semanas de intervenção, o tratamento funcional reduziu a concentração plasmática de LDL-C (-13.7% ± 3.7, p=0.002) e proteína C-reativa (-35.5% ± 5.9, p=0.027). Triglicerídeos (- 15.68% ± 5.94, p=0.02) e malondialdeído (-40.98% ± 6.74, p=0.04) foram reduzidas apenas em subgrupos de indivíduos que apresentavam valores basais acima da mediana (93 mg/dL e 2.23 umol/L, respectivamente). A análise de latosterol e campesterol no plasma sugeriu que a intensidade da redução de LDL-C não foi influenciada pela síntese endógena de colesterol, mas sim pela taxa de absorção. Após análise multivariada dos resultados, pacientes identificados como \"good responders\" à suplementação (n=10) foram recrutados para um estudo piloto de redução da dosagem da estatina, aliado à terapia dietética complementar. Estes pacientes receberam o tratamento funcional por 12 semanas: durante as 6 primeiras semanas mantevese a dosagem de estatina, que em seguida foi reduzida em 50% das semanas 6 a 12. Não foram observadas diferenças para os marcadores plasmáticos de lipídeos, inflamação, capacidade de efluxo de colesterol ou número de partículas de HDL após a redução da dose de estatina, quando comparada à terapia convencional. Embora limitado pelo reduzido número de pacientes, o estudo demonstra o potencial para uma nova abordagem terapêutica, combinando reduzida dose de estatina com específicos compostos bioativos. Esta pode ser uma importante alternativa para muitos pacientes em risco cardiovascular e que são intolerantes à terapia com altas doses de estatina.

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Introdução: As estatinas são drogas amplamente utilizadas na prevenção primária e secundária de doenças cardiovasculares, por reduzirem o nível de colesterol. Porém alguns pacientes podem apresentar elevação da creatinofosfoquinase (CPK) e sintomas musculares relacionados ao seu uso. Além da CPK, outros marcadores de dano muscular podem apresentar alterações. Este estudo analisou a concentração dos marcadores bioquímicos, CKMB e anidrase carbônica III (CAIII) e sua relação com a presença de miosite. Métodos: Foram selecionados pacientes em tratamento com estatinas e com elevação da CPK. Foram realizadas as determinações de CKMB e CAIII e analisadas as variáveis clínicas e laboratoriais destes pacientes. Resultados: Cerca de 10% dos pacientes em tratamento com estatina apresentaram elevações de CPK acima 1x o limite superior de normalidade (LSN). Desses, 50,4% apresentaram sintomas musculares, definido como miosite. O uso de sinvastatina [OR=2,24 (IC95%:1,47-3,42)], o índice de massa corpórea > 28 Kg/m2 [OR=1,06 (IC95%: 1,01-1,10)] e a CKMB > 1xLSN [OR=1,59 (IC95%: 1,02-2,49)] apresentaram-se como preditores independentes para a ocorrência de miosite. A CKMB aumentada foi observada em 36,2% dos pacientes (7,17±4,4 ng/mL). Os pacientes com e sem miosite apresentaram valores semelhantes de CAIII (211,3±93,4pg/mL vs 204,0±84,6pg/mL; p=0,549). Pacientes diabéticos apresentaram elevações significantes de CKMB em relação aos não diabéticos (4,8±4,6ng/mL vs 3,5±2,4ng/mL; p=0,0006) e não apresentaram diferenças quanto à presença de miosite. Conclusão: A CKMB apresentou alteração em parte dos pacientes tratados com estatinas e foi um preditor independente para a presença de miosite. A CAIII não foi considerada um bom marcador de dano muscular na população deste estudo / Introduction: Statins are drugs widely used in primary and secondary prevention of cardiovascular diseases, due to the decreasing effect on cholesterol level. However, some patients may present elevated levels of creatine phosphokinase (CK) and muscle symptoms related to statin use. In addition to CK, other markers of muscle damage may present changes. This study analyzed the concentration of biochemical markers, CKMB and carbonic anhydrase III (CAIII) and related them to the presence of myositis. Methods: Patients on statin therapy and CK elevation were selected. CKMB and (CAIII) assays were performed and the clinical and laboratory variables of these patients were analyzed. Results: About 10% of the patients receiving statin therapy (6692) presented CK elevations above 1x upper reference limit (URL). Muscular symptoms, defined as myositis, were presented in 50.4% of these patients. Use of simvastatin [OR=2,24 (IC95%:1,47-3,42)], a body mass index > 28 kg / m2 [OR = 1.06 (95% CI: 1.01-1, 10)] and a concentration of CKMB > 1x URL [OR = 1.59 (95% CI: 1.02-2.49)] presented as independent predictors for the occurrence of myositis. Increased CKMB was observed in 36.2% of patients (7.17 ± 4.4 ng / mL). Patients with and without myositis had similar CAIII values (211.3 ± 93.4pg / mL vs 204.0 ± 84.6pg / mL, p = 0.549). Diabetic patients showed significant elevations of CKMB compared to non-diabetic patients (4.8 ± 4.6 ng / mL vs. 3.5 ± 2.4 ng / mL, p = 0.0006) and did not present differences regarding the presence of myositis. Conclusion: CKMB level changed in part of the patients treated with statins and this enzyme was an independent predictor for the presence of myositis. CAIII was not considered a good marker of muscle damage in the studied population

As doenças cardiovasculares (DCV) são responsáveis pelas principais causas (dislipidemias e hipertensão arterial) de morte, sendo que o tratamento convencional é feito com estatina. Hoje alguns componentes presentes em alimentos tem sido apontados como alternativas ou coadjuvantes no tratamento. O objetivo deste trabalho foi avaliar as concentrações séricas de colesterol e suas frações, triglicérides e pressão arterial em humanos. O estudo foi conduzido em três tratamentos (placebo, estatina e ω-3) com dieta de 1200 calorias por dia. Os grupos com oito pacientes cada tratamento, foram avaliados no tempo zero e 30 dias. Nos três tratamentos houveram reduções no peso, porém não houve mudanças significativas no IMC. A circunferência de cintura (CC) diminuiu aproximadamente 3 cm em todos os tratamentos. Para a circunferência do quadril (CQ) maior diminuição foi no tratamento estatina (redução de 2,44 cm). Não houve diferença em nenhum dos tratamentos para relação circunferência cintura-quadril (CCQ). As concentrações de colesterol total diminuiu 41%; 11,38% e 5% para os tratamentos estatina, dieta e ω-3, respectivamente. Para o HDL-C o tratamento estatina aumentou 10,09%, dieta diminuiu 9,65% e ω-3 não promoveu mudança nos valores. Para LDL-C os tratamentos estatina e ω-3 reduziram 49% e 3,03%, respectivamente, porém o tratamento dieta aumentou 3,46%. Para os triglicérides os tratamentos com dieta, estatina e ω-3 diminuíram 28,05%, 18,95% e 13,45% , respectivamente. A pressão arterial sistólica (PAS) e pressão arterial diastólica (PAD) no tratamento estatina diminuíram 3,52% e 4,60%, respectivamente. No tratamento dieta a redução foi de 1,82% e 5,14% na PAS e PAD, respectivamente. Já no tratamento ω-3 houve discreto aumento tanto na PAS (11,30%) quanto na PAD (9,87%). Com isso conclui-se que houve diminuição significativa na medida da circunferência do quadril. Nos três tratamentos o peso, IMC, circunferência de cintura, coeficiente cintura-quadril, concentrações de colesterol, HDL-c, LDL-c, triglicérides, PAS e PAD não influenciaram significativamente nos resultados obtidos durante o experimento. / The cardiovascular diseases are responsible for the main causes (dislipidemias and arterial hypertension) of death, being that the conventional treatment is make with statin. Today some compoments presents in food it was been pointed as alternatives or coadjutants in treatment. The objective of this research was to evaluate the concentration control of cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and arterial pressure in humans. The study was divided in three treatments (placebo, statin and ω-3) with diet of 1,200 calories by day to every groups with eight patients each treatment, appraised in time zero and thirty days. This study showed that all the treatments had reductions of weight, but it wasn't verified changes significative in BMI. The circumference waist decreased approximately three centimeters in all the treatments, to the circumference hip there was a larger decrease in statin treatment (reduction of 2.44 centimeter). For the waist-hip circumference there wasn't difference in all the treatments. The total cholesterol had decrease of 41%; 11.38% and 5% to statin, diet and ω-3 treatments, respectively. For the HDL-cholesterol the statin treatments increased 10.09%, diet decrease 9.65% and ω-3 not promoted change in values. In LDL-cholesterol the statin and ω-3 treatments decrease 49% and 3.03%, respectively, but the diet treatment increased 3.46%. For the triglycerides the diet, statin and ω-3 treatments decrease 28.05%; 18.95% and 13.45%, respectively. The systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) in statin treatment decrease 3.52% and 4.60%, respectively. In the diet treatment the decrease was of 1.82% and 5.14% in SAP and DAP, respectively. In ω-3 treatment there was a discreet increase as much SAP (11.30%) as DAP (9.87%). With this concluded that the hip circumference showed difference statistical. In three treatments the weight, BMI, waist circumferences, waisthip circumference, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, SAP and DAP wasn't difference in experiment.

Adherence to guideline-recommended secondary cardiovascular prevention therapy (statins and cardiac rehabilitation) has been demonstrated to reduce the risk of all-cause mortality (Statins RRR 0.25, 95% CI 0.19-0.30; Cardiac Rehabilitation RRR 0.26, 95% CI 0.14-0.36) and secondary events.1,2 Yet, ≥50% of patients discontinue statin use within 12-month after an initial prescription and completion of cardiac rehabilitation is ≤20% in Ontario.3,4 Low statin adherence and cardiac rehab completion limits patients from realizing the full benefits of therapy. A meta-analysis of randomized controlled trials of adherence to statins for secondary prevention reported that nonadherence to statins was greater in non-white ethnicities compared to white ethnicities (OR 1.28, 95% CI 1.04-1.59) with geographical variation in outcomes.5 In respect to cardiac rehabilitation, the literature suggests that non-white ethnicities are less likely to complete cardiac rehabilitation compared to white participants.6,7 However, a gap remains in our knowledge of cardiac rehabilitation completion among immigrants due to lack of outcome reporting across clinical trials. The literature suggests that immigrants have improved health profiles relative to Canadian-born patients. Specifically, immigrants with ≤10 years of Canadian residency have greater medication adherence than immigrants with >10 of Canadian residency when compared to Canadian-born participants.6-9 This thesis was a planned sub-study of the Interventions Supporting Long-Term Adherence and Decreasing Cardiovascular Events (ISLAND) randomized control trial. The ISLAND study was a pragmatic, randomized controlled trial investigating the effect of educational reminders on adherence to guideline-recommended therapy post-myocardial infarction. Study participants were allocated in a 1:1:1 ratio to one of three groups: i) usual care, ii) educational reminders sent via post, or iii) combination post and interactive voice response educational reminders. Investigators were blinded to the allocation sequence, participant allocation, and outcome assessment. Medication adherence and completion of cardiac rehabilitation were assessed 12-months from baseline. This sub-study of ISLAND focused on participants who completed a 12-month outcome assessment with a recorded response to the following question, “Were you born a Canadian citizen?”. Immigrants experienced greater odds of statin adherence at 7-days (OR 1.36, 95% CI 1.00-1.85) and 30 days (OR 1.36, 95% CI 0.96-1.94) at one-year post-myocardial infarction, after adjusting for age, diabetes, sex, and smoking status. We found no evidence that immigration status was associated with cardiac rehabilitation completion (OR 0.91, 95% CI 0.72-1.14) after adjusting for age, diabetes, sex, smoking status, average neighborhood income quintile, education, and marital status. The odds of statin adherence at 7-days (OR 1.33, 95% CI 0.89-2.18) and 30-days (OR 1.39, 95% CI 0.89-2.18) was greater in visual minorities than white patients, however the difference was not statistically significant. We found no evidence of an association between ethnicity and cardiac rehabilitation completion (OR 0.98, 95% CI 0.75-1.29). Our analysis could not fully evaluate the healthy immigrant effect due to an insufficient sample size of immigrants with <10 years of Canadian residency exposure (n=29). In conclusion, we report a statistically significant 36% increase in the odds of 7-day and 30-day statin adherence in immigrants compared to Canadian-born patients. We also report that the odds of cardiac rehabilitation decreased by 9% in immigrants compared to Canadian-born patients at 12-months post-myocardial infarction but this was not statistically significant. Our findings offer support for the “healthy immigrant effect” continuing in immigrants with >10 years of Canadian residency exposure. We were unable to evaluate outcomes in immigrants with <10 years Canadian residency exposure due to a lack of sample size (n=29). / Thesis / Master of Science (MSc) / The primary purpose of this research project was to assess whether immigrants, individuals who reside in Canada but were born outside of the country, who have experienced a previous heart attack were adhere to heart health therapies better than Canadian-born patients. The heart health therapies of interest to our investigation are two guideline-recommended heart attack prevention therapies, statins and cardiac rehabilitation. The study design of our research project was a cohort sub-study of the ISLAND randomized control trial which investigated adherence to heart health therapies in patients residing in Ontario, Canada. Our major finding was that immigrants who lived in Canada for >10 years were more adherent to statin therapy for a previous heart attack compared to Canadian-born participants. Our findings support the hypothesis that immigrants tend to demonstrate behaviours associated with improved outcomes compared to their Canadian-born counterparts.

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