Avaliação econômica do uso de ômega-3 na redução dos fatores de risco cardiovascular: análise de custo-efetividade / Economic evaluation of omega-3 use in cardiovascular risk reduction factors: cost-effectiveness analysis

INTRODUÇÃO: As doenças cardiovasculares (DCV) aparecem em primeiro lugar entre as principais causas de mortalidade no mundo, representando 46,2% do total de mortes, número muito próximo aos encontrados no Brasil, impactando os gastos com saúde. A prevenção baseia-se em estilo de vida saudável, contudo, uma vez instaladas, é consenso o tratamento medicamentoso com estatinas. Alguns tratamentos alternativos vêm sendo estudados como o ômega-3 (w-3) na prevenção das DCV. Apesar das evidências clínicas favoráveis, não existem muitos estudos acerca da viabilidade econômica de tais tratamentos. OBJETIVO: Avaliar o custo-efetividade das intervenções com w-3 isolado ou associado às estatinas na redução dos fatores de risco cardiovascular sob a perspectiva do Sistema Único de Saúde (SUS). MATERIAL E MÉTODOS: Para avaliar a efetividade do w-3 isolado e combinado com estatina foram utilizados os dados secundários do ensaio clínico CARDIONUTRI no momento basal e após 8 semanas. A amostra foi composta por 186 indivíduos com idade entre 30 e 74 anos divididos entre aqueles que não tomavam medicação e os que tomavam estatinas. Aleatoriamente, uma parcela deles recebeu cápsulas de 1 g de w-3 (37% de ácido eicosapentaenoico e 23% de docosaexaenoico) ou cápsulas de placebo. A recomendação era de que todos deveriam tomar 3 cápsulas ao dia, totalizando 3g/dia (de w-3 ou placebo) durante 8 semanas. Ao final, obteve-se quatro grupos: a) w-3; b) placebo; c) w-3 + estatina; e d) estatina. Para a avaliação do impacto foi usado o método Diferenças em Diferenças com a adição de variáveis de controle: densidade calórica do consumo alimentar, Índice de Massa Corporal (IMC), prática de atividade física, idade, sexo, raça, hábito tabagista, escolaridade e grau de adesão. Os custos dos tratamentos foram estimados com base no custo médio ponderado pelas probabilidades das eventuais intercorrências relacionadas a efeitos adversos e de sucesso e fracasso por meio do método da árvore de decisão. Foi considerado para fins do cômputo dos custos o período de 2 meses de tratamento. RESULTADOS: Nos quatro grupos, a maioria eram mulheres, obesas e com escore de risco muito alto para DCV. Os grupos w-3 e placebo possuíam maior escolaridade e renda comparadas a aqueles que tomavam estatinas. Todas as variáveis de controle foram estatisticamente significantes em pelo menos um dos modelos, exceto raça. A suplementação com w-3 associada às estatinas mostrou efetividade sobre HDLPEQUENA, com diminuição de 2,211 mg/dL e custo-efetividade de R$ 109,31 por redução em mg/dl da lipoproteína em 2 meses de tratamento. CONCLUSÃO: O tratamento com 1,8g de óleo de peixe isolado ou associado às estatinas em intervenção primária não evidenciou efeitos significativos nas mudanças dos parâmetros lipídicos, exceto no caso da HDLPEQUENA com o tratamento associado, mostrando não ser custo-efetivo na redução dos fatores de risco cardiovascular em geral. Em virtude da existência de controvérsias acerca de seus potenciais efeitos, sugere-se que os ensaios clínicos utilizem métodos estatísticos mais robustos para avaliar o impacto líquido da suplementação

INTRODUCTION: Cardiovascular diseases (CVD) are among the leading causes of death worldwide, accounting for 46.2% of all cases, very close to those found in Brazil, impacting health expenses. Current prevention is based on a healthy lifestyle, and once a CVD diagnosis is made, the current consensus is drug treatments with statins. Some alternative treatments such as omega-3 (w-3) have been studied in the prevention of these diseases. However, despite favorable clinical evidence, there are not many studies of economic viability of this treatment. OBJECTIVE: To evaluate the cost-effectiveness of interventions with w-3 alone or associated with statins in reducing cardiovascular risk factors from the perspective of the Unified Health System (SUS). METHODS: To assess the effectiveness of w-3 alone and its combination with statin, the secondary data of the classic lipid profile and lipoprotein size of the CARDIONUTRI clinical trial were used at baseline and after 8 weeks. The sample consisted of 186 subjects aged 30 to 74 years randomly received capsules containing 3g of w-3 per day (37% of eicosapentaenoic acid and 23% of docosahexaenoic acid) or 3g of mineral oil (placebo). Capsules were randomly assigned to individuals who were not taking medication or were already taking statins, separated into four groups: a) w-3; b) placebo; c) w-3 associated with statins; d) statins. Data analysis was conducted using the Difference in Differences statistical method with the addition of control variables: caloric density of food consumption, Body Mass Index (BMI), physical activity practice, age, sex, race, smoking, educational level and adherence to the treatment. The treatment costs were estimated based on the weighted average cost by the probabilities of the eventual intercurrences related to adverse effects and of success and failure by means of the decision tree method elapsed in 2 months of treatment. RESULTS: In all four groups, the majority were women, obese and with a very high-risk score for CVD. W-3 and placebo groups had higher educational level and income compared to those who were already taking statins. All control variables were statistically significant in at least one of the models except race. W-3 supplementation showed efficacy on HDLSMALL among those who consumed w-3 + statins with a reduction of 2,211 mg /dL and cost-effectiveness R$ 109.31 per mg/dL for 2 months of treatment. CONCLUSION: The treatment with 1.8g of fish oil isolated or associated with statins in primary intervention did not show significant effects on changes in lipid parameters except HDLSMALL of interventions associated with statins. Therefore it was not cost-effective in reducing cardiovascular risk factors. Due to the existence of controversies about its potential effects, it is suggested that clinical trials use more robust statistical methods to assess the net impact of supplementation

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Zaluzania montagnifolia: essential oil composition and biological properties / Zaluzania montagnifolia: composición del aceite esencial y actividades biológicas

The chemical composition of the seasonal essential oils (2015-2016) from the leaves and flowers of Zaluzania montagnifolia is presented. The chemical content of those oils showed quantitative and qualitative differences. Germacrene D (19.9-29.8%), camphor (12.4- 19.4%) and ß-caryophyllene (13.7-18.5%) were the most abundant volatiles in the leaves. The essential oils from the flowers contained high amounts of camphor (32.7-37.2%) limonene (19.8-24.9%) and germacrene D (3.2-7.3%). All the seasonal essential oils showed a potent in vitro inhibition against HMG-CoA reductase. The essential oils from flowers (IC50, 40.5-55.1 µg mL-1) showed better inhibition properties than those of leaves (IC50, 84.4-123.5 µg mL-1). Camphor (IC50, 72.5 µg mL-1) and borneol (IC50, 84.4 µg mL-1) exerted a non-competitive inhibition on the enzyme. Additionally, the hydrodistillates exhibited antibacterial activity against the phytopathogenic Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) and P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). Germacrene D (MIC, 35.4-66.2 µg mL-1) and ß-caryophyllene (MIC, 36.5-54.2 µg mL-1) were the strongest anti-Pseudomonas syringae agents.

Se presenta la composición química de los aceites esenciales estacionales (2015-2016) provenientes de hojas y flores de Zaluzania montagnifolia. El contenido químico de los aceites esenciales mostró diferencias cualitativas y cuantitativas. El germacreno D (19.9-29.8%), alcanfor (12.4-19.4%) y ß-cariofileno (13.7-18.5%) fueron los volátiles más abundantes en las hojas. Los aceites esenciales de las flores contuvieron altas concentraciones de alcanfor (32.7-37.2%), limoneno (19.8-24.9%) y germacreno D (3.2-7.3%). Todos los aceites esenciales estacionales mostraron una potente inhibición in vitro contra la HMG-CoA reductasa. Los aceites esenciales de las flores (IC50, 40.5-55.1 µg mL-1) mostraron mejores propiedades inhibitorias que aquellos de las hojas (IC50, 84.4-123.5 µg mL-1). El alcanfor (IC50, 72.5 µg mL-1) y el borneol (IC50, 84.4 µg mL-1) ejercieron una inhibición no competitiva sobre la enzima. Adicionalmente, los hidrodestilados exhibieron una actividad antibacterial contra los fitopatógenos Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) y P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). El germacreno D (MIC, 35.4-66.2 µg mL-1) y ß-cariofileno (MIC, 36.5-54.2 µg mL-1) fueron los agentes más fuertes contra los patovares de Pseudomonas syringae.

Miopatía por estatinas y vitamina D / Statin-Related Myopathy and Vitamin D

Las estatinas son fármacos habitualmente seguros y bien tolerados, muy eficaces para la prevención de trastornos cardiovasculares. La presencia de mialgias, poco frecuente, pero con incidencia dispar en diversos reportes, es una de las causas de abandono de su uso. También las distintas denominaciones (mialgia, miopatía, rabdomiólisis) y la subjetividad de cada paciente para referirlas han creado confusión en el tema. Se ha comenzado a reportar asociación entre niveles de vitamina D sérica disminuida y mayor riesgo de miopatía, por un lado, y trabajos donde pacientes que las abandonaban a causa de mialgias, con deficiencia de vitamina D, pueden tolerarlas una vez que se suplementa la vitamina hasta valores deseables. La presencia de polimorfismos en genes de enzimas que metabolizan o transportan a las estatinas es otro factor claramente relacionado con miopatía. Es posible que el déficit de vitamina D deba ser considerado un factor de riesgo para desarrollar miopatía por estatinas, como lo serían también la administración simultánea de fármacos que se metabolizan por la misma vía de citocromo P450, o la presencia de los polimorfismos mencionados. En conclusión, el hallazgo de tener deficiencia de vitamina D se asocia a miopatía por estatinas, o que es un factor de riego para desarrollarla, abre nuevas perspectivas para un gran número de pacientes que abandonan este tratamiento debido a esta patología. (AU)

Statins are usually safe and well tolerated drugs, very effective for preventing cardiovascular complications. The rare presence of myalgia, with different incidence as reported by several studies, is one of the causes of lack of drug compliance. Also the different symptoms referred (myalgia, myopathy, rhabdomyolysis) and the lack of objetivity of each patient when referring to the symptoms, have created confusion in this matter. Associations between decreased vitamin D levels and increased risk of myopathy has been reported. Indeed, studies describing patients with vitamin D deficiency who are not compliant due to myalgia show that they become tolerant to the drugs once the vitamin is supplemented to desirable values. The presence of gene polymorphisms for enzymes that metabolize or transport statins is another factor clearly related to myopathy. Therefore, we should consider vitamin D deficiency and other conditions such as the simultaneous administration of drugs that are metabolized by the same cytochrome P450 pathway, or the presence of mentioned polymorphisms as a risk factor for developing myopathy due to statins. In conclusion, the finding that vitamin D deficiency is associated with statin myopathy, or is a risk factor its develpoment, opens new perspectives for a large number of patients who leave this treatment due to this condition. (AU)

Statins and bonehealth: a mini review / Estatinas y salud ósea: una minirevisión

Statins are a widely prescribed class of medications that inhibit similar pathways as the anti-resorptive bisphosphonate drugs. Statins target the mevalonate pathway by blocking HMG-CoA reductase. Several recent meta-analyses concluded statins are osteoprotective in the general population. Here we present current literature exploring the mechanisms underlying the putative osteoprotective effects of statins. We also review recent clinical studies, ranging from observational cohort studies to randomized clinical trials, testing the effect of statins on bone health in various populations. (AU)

Las estatinas son un grupo de drogas prescriptas en forma habitual, con la capacidad de bloquear vías de señalización similares a las inhibidas por los amino-bisfosfonatos. Las estatinas inhiben la vía del mevalonato, a través del bloqueo de diferentes enzimas. Varios metaanálisis recientes llevaron a la conclusión de que las estatinas tienen capacidad osteoprotectora en la población general. En esta revisión presentamos la literatura actual describiendo los mecanismos que subyacen en el potencial efecto osteoprotector de las estatinas, como así también estudios observacionales y clínicos aleatorizados sobre el efecto de estatinas en la salud ósea en diversas poblaciones. (AU)

Glycemic effects of simvastatin: Where do we stand?

ABSTRACT In clinical practice, simvastatin is usually used in the treatment of dyslipidemia patients and those at risk of or with established cardiovascular disease. However, previous studies have shown that simvastatin has the potential to affect glycemic parameters as it reportedly reduced insulin secretion and sensitivity. The exact mechanism by which simvastatin affects glycemia is still unknown, but previous studies have postulated the involvement of the glucose-insulin secretion mechanism. This review focuses on the effects of simvastatin, either alone or in combination with other lipid lowering agents, antidiabetics and antihypertensives, on glucose homeostasis. Some studies have reported that simvastatin might impair the levels of glucose metabolism markers in the blood while others have reported no effect or improvement in glycemia.

Treatment of experimental periodontal disease by laser therapy in simvastatin-modified rats

Abstract Low intensity laser can be used as a promising alternative in the treatment of periodontal disease. Objective The aim of this study was to evaluate low-level laser therapy (LLLT) as an adjuvant treatment for scaling and root planing (SRP) for the treatment of induced periodontitis in simvastatin-modified rats. Material and Methods A total of 180 rats were evenly divided into two groups: Veh - receiving oral administration of polyethylene glycol (vehicle); S - receiving oral administration of Simvastatin. Periodontal disease was induced in both groups at the first mandibular molar. After seven days, the ligature was removed and the animals were divided into subgroups according to the following local treatments: NT - no treatment; SRP - scaling and root planing and irrigation with saline solution; and LLLT ¬- SRP and laser irradiation (660 nm; 0.03 W; 4 J). Ten animals in each subgroup/local treatment were euthanized at 7, 15 and 30 days. Samples of gingival tissue were processed to analyze the tissue oxidative damage and radiographic analysis. Levels of oxidative stress were analyzed by the expressions of Tripeptideglutathione (TG), Malondialdehyde (MDA) and Carbonylated Proteins (CP). Results The animals in S group had higher levels of TG and lower levels of MDA and CP compared with Veh group (p<0.05). Radiographically, in the intragroup analysis Veh and S, LLLT showed lower bone loss (BL) compared with NT and SRP, in all experimental periods (p<0.01). In addition, a lower BL was observed for the animals of Veh group treated with LLLT compared with treatment SRP in the S group, in all experimental periods. Conclusion Within the limits of this study, we can conclude that LLLT was effective as adjuvant treatment for SRP protecting against the occurrence of oxidative tissue damages as well as for reducing alveolar bone loss in experimentally induced periodontitis simvastatin-modified rats.

Effects of statins on the development of sepsis and organ dysfunction in hospitalized older patients in China

ABSTRACT This study aimed to evaluate the protective role of statins on the development of sepsis and infection-related organ dysfunction and mortality in a hospitalized older Chinese population with bacterial infections. In this retrospective cohort study, 257 older patients with bacterial infection were divided into two groups: a statin group, those who had received statin therapy for ≥1 month before admission and continued receiving statin during hospitalization; and a non-statin group, those who had never received statin or used statin for <1 month prior to admission. A multivariate logistic regression analysis was performed to identify risk and protective factors for severe sepsis. A significantly lower incidence of organ dysfunction was found in the statin group, as compared with the non-statin group (13.3% vs 31.1%, respectively; p = 0.002), corresponding to adjusted rates ratio of 0.32 (95% confidence interval [CI], 0.13-0.75; p = 0.009). No significant difference was found between statin and non-statin groups in 30-day sepsis-related mortality (4.4% vs 10.2%, respectively; p = 0.109), incidence of intensive care unit admission (13.3% vs 16.8%, respectively; p = 0.469), or length of hospital stay (20.5 vs 25.9 days, respectively; p = 0.61). Statins significantly reduced the development of sepsis and infection-related organ dysfunction in hospitalized older Chinese patients but did not reduce 30-day mortality, ICU admission incidence, or length of hospital stay.

Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells

Abstract: The aim of this study was to evaluate the bioactivity and cytocompatibility of simvastatin (SV) applied to MDPC-23 odontoblast-like cells. For this purpose, MDPC-23 cells were seeded in 96-well plates and submitted to treatments with 0.01 or 0.1 μM of SV for 24 h, 72 h or continuously throughout the experimental protocol. The negative control group (NC) was maintained in DMEM. Cell viability (MTT), ALP activity (thymolphthalein monophosphate), and mineralized matrix deposition (alizarin red) were analyzed at several time points. The data were submitted to ANOVA and Tukey's test (α = 0.05). Although cell viability was observed in the groups treated with SV, these groups did not differ from the NC up to 7 days. There was a reduction in cell viability for the groups treated with 0.1 μM of SV for 72 h, and submitted to continuous mode after 14 days. A significant increase in ALP activity occurred in the group treated with 0.01 μM of SV for 24 h, compared with the NC; however, only the group treated with 0.1 μM of SV in continuous mode reduced the ALP activity, in comparison with the NC. After 14 days, only continuous treatment with 0.1 μM of SV did not differ from NC, whereas the other experimental groups showed increased mineralized matrix deposition. Thus, it was concluded that low concentrations of simvastatin were bioactive and cytocompatible when applied for short periods to cultured MDPC-23 odontoblast-like cells.

Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line / Pravastatina induz parada no ciclo celular e diminuição na produção de VEGF e bFGF em linhagem de Mieloma Multiplo

Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.

Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.

Single-nucleotide polymorphisms: a perspective of cardiovascular prevention / Polimorfismos de nucleotídeo único: uma perspectiva de prevenção cardiovascular

Summary Introduction: several studies have evaluated the utilization of lipid biomarkers in an attempt to correlate them with clinical cardiovascular events. Nevertheless, the investigation of clinical conditions under specific plasmatic levels of lipoproteins for long periods presents limitations due to inherent difficulties that are related to the follow-up of individuals throughout their lives. Better understanding of the clinical response and occasional resistance to the action of hypolipidemic drugs in several clinic scenarios is also necessary. Objectives: to determine the role of evaluation of single-nucleotide polymorphisms (SNPs) related to the metabolism of lipids, and its implications in different clinical scenarios. Methods: a search of the literature in English and Spanish languages was performed in Medline, Lilacs via Bireme, IBECS via Bireme, and Cochrane databases. The expected results included information regarding plasmatic lipid profile and SNPs, cardiovascular clinical outcomes and polymorphisms related to the effectiveness of statins in the treatment of hypercholesterolemia. Results: in order to perform this analysis, 19 studies were included from a total of 89 identified citations. The evaluation of the results suggests that low plasmatic levels of LDL-c are associated with a reduction in the risk of heart attacks, although this was not observed for the rise of plasmatic levels of HDL-c. Conclusion: polymorphisms in different populations and clinical perspectives may bring important contributions for a better understanding and adequacy of plasmatic lipoproteins aiming at reducing cardiovascular risk.

Resumo Introdução: muitos estudos tem avaliado a utilização de biomarcadores lipídicos na tentativa de correlacioná-los com eventos clínicos cardiovasculares. Contudo, a investigação de condições clínicas sob níveis plasmáticos específicos de lipoproteínas por longos períodos, apresenta limitações devido às dificuldades inerentes relacionadas ao acompanhamento de indivíduos ao longo de suas vidas. Adicionalmente, há a necessidade de melhor compreensão da resposta clínica e eventual resistência da ação de drogas hipolipemiantes em diversos cenários clínicos. Objetivos: determinar o papel da avaliação de polimorfismos de nucleotídeo único (SNPs) relacionadas com o metabolismo lipídico e suas implicações em diferentes cenários clínicos. Métodos: foi realizada uma pesquisa na literatura de língua inglesa e espanhola nas bases de dados Medline, Lilacas via Bireme, IBECS via Bireme e Cochrane. Os resultados esperados incluíam informações sobre o perfil lipídico plasmático e SNPs, desfechos clínicos cardiovasculares e polimorfismos relacionadas à efetividade de estatinas quanto ao tratamento da hipercolesterolemia. Resultados: para esta análise foram incluídos 19 estudos de um total de 89 citações identificadas. Os dados resultantes e avaliados sugerem que baixos níveis plasmáticos de LDL-c estão associados com redução do risco de infarto do miocárdio o que não foi observado para o aumento nos níveis plasmáticos de HDL-c. Conclusão: os polimorfismos em diferentes populações e perspectivas clínicas podem trazer importantes contribuições para a melhor compreensão e adequação de metas de lipoproteínas plasmáticas que visem a redução de risco cardiovascular.

Cambios del estado clínico periodontal según consumo sistémico de estatinas / Changes in clinic periodontal status according to systemic statins intake

Objetivos: Describir los cambios del estado clínico periodontal de pacientes según el consumo sistémico de estatinas por indicación del cardiólogo. Material y método Se realizó un estudio descriptivo en el cual se reclutaron pacientes con periodontitis crónica derivados desde cardiología de la Clínica Dávila. Un grupo de ellos iniciaría terapia de estatinas. Se realizaron mediciones clínicas periodontales de profundidad al sondaje (PS), nivel de inserción clínico, índice de sangrado, área de superficie periodontal inflamada, e índice gingival, al inicio (antes de comenzar la terapia de estatinas) y 6 meses después. Los datos fueron analizados utilizando estadística descriptiva. Resultados Diez pacientes participaron del estudio, 5 con indicación de estatinas. El grupo con estatinas en comparación con el grupo sin estatinas presentó una disminución en promedio: de PS (0,4 mm versus 0,13 mm); porcentaje de sitios con PS > 5 mm (4,16 por ciento versus 1,09 por ciento); de nivel de inserción clínico (0,5 mm versus 0,2 mm), índice de sangrado (27,16 por ciento versus 8,8 por ciento) y área de superficie periodontal inflamada (305,68 mm2 versus 121,35). Conclusiones Estos resultados sugieren que pacientes con periodontitis crónica podrían obtener beneficios de la terapia sistémica con estatinas. Se requiere de estudios clínicos con asignación aleatoria y el óptimo tamaño muestral que comprueben el efecto e impacto de las estatinas sobre el estado periodontal.

Objective: To describe changes in periodontal clinical status of patients according to systemic statin use prescribed by a cardiologist. Material and methods A descriptive study was performed on patients with chronic periodontitis referred from the Department of Cardiovascular Diseases of Dávila Clinic. A group of them began statin therapy. Clinical measurements of periodontal probing depth (PD), clinical attachment level, bleeding index, periodontal inflamed surface area, and gingival index, were performed at baseline (before starting statin therapy) and 6 months later. Data were analyzed using descriptive statistics. Results A total of 10 patients participated in the study, and five of them received statin therapy. The statin group compared to the group without statins, showed a mean decrease in: PD (0.4 mm versus 0.13 mm); percentage of PS sites > 5 mm (4.16 percent versus 1.09 percent); clinical attachment level (0.5 mm versus 0.2 mm), bleeding index (27.16 percent versus 8.8 percent), and periodontal inflamed surface area (305.68 versus 121.35 mm2). Conclusions These results suggest that patients with chronic periodontitis may benefit from systemic therapy with statins. Randomized clinical trials with optimal sample size are required to check the effect and impact of statins on the periodontal status.

The effect of simvastatin on relapse of tooth movement and bone mineral density in rats measured by a new method using microtomography

PURPOSE: To evaluate the effect of simvastatin on relapse of tooth movement in rats using microtomography (micro CT), as well as the correlation of bone density with the orthodontic relapse. METHODS: Twenty-five adult male Wistar rats, divided into two groups, had stainless steel springs installed on left maxillary first molar. The molars were moved for 18 days, and after removing the springs, were applied by oral gavage, 5mg/kg of simvastatin in the experimental group for 20 days. Tooth relapse was assessed with a micro CT scanner, and the images chosen through the Data Viewer software 1.5.0.0 had their measurement guides made and checked by the software Image ProR plus 5.1, and compared by Mann-Whitney test. After rats were sacrificed, bone mineral density was evaluated by micro CT through the software CT Analyzer 1.13 and compared by independent T-test, as well as by Spearman correlation test. RESULTS: Relapse and bone mineral density (BMD) was lower in the experimental group than in the control group, however without a statistically significant difference. CONCLUSION: Simvastatin did not inhibit the relapse of tooth movement in rats, and there was no correlation between bone density and orthodontic relapse. .

Maternidade atrás das grades: em busca da cidadania e da saúde. Um estudo sobre a legislação brasileira / Motherhood behind bars: the struggle for citizens' rights and health for women inmates and their children in Brazil / La maternidad entre rejas: en búsqueda de la ciudadanía y de la salud. Un estudio sobre la legislación brasileña

Este estudo analisa as conexões entre saúde, direitos, legislação e políticas públicas a partir da pesquisa documental realizada no âmbito federal e nos estados do Rio Grande do Sul, Mato Grosso, Paraná e São Paulo, acerca das garantias legais das mulheres e seus filhos que vivem no cárcere. Busca instrumentalizar uma atuação garantista dos agentes públicos e dar visibilidade à problemática, diante das extremas vulnerabilidades e invisibilidade jurídica e administrativa da questão. Foram identificadas 33 normas legais, com pontos de tensão, como a possibilidade de prisão domiciliar e as disparidades quanto a prazos e condições de permanência das crianças no sistema penitenciário. A garantia legal constitucional do direito à amamentação é refletida nas regulamentações identificadas. Mas constatam-se ausências de outros aspectos relativos à maternidade na prisão, que se traduzem em dupla penalidade às mulheres, arbitrariamente estendida aos seus filhos. É necessária a ampliação e efetivação da regulamentação existente para prevenir e coibir as violações de direitos apontadas.

This study analyzes the links between health, rights, legislation, and public policies based on document research on legal safeguards for women and their children residing in prison. The research was conducted at the Federal level and in four States of Brazil: Rio Grande do Sul, Mato Grosso, Paraná, and São Paulo. The study aims to back measures by public agencies to guarantee such rights and to raise awareness of the problem, given the extreme vulnerability of women inmates and their children and the issue's legal and administrative invisibility. The authors identified 33 different legal provisions as points of tension, such as the possibility of house arrest and disparities in the terms and conditions for children to remain inside the prison system. Various provisions cite the Constitutional guarantee of women inmates' right to breastfeed in prison. Meanwhile, the study found gaps in other issues pertaining to motherhood in prison, expressed as dual incarceration (imprisonment arbitrarily extended to their children). It is necessary to expand and enforce the existing legislation to prevent such violations of rights.

Este estudio analiza las conexiones entre la salud, derechos humanos, legislación y políticas públicas, partiendo de una investigación documental, realizada a nivel federal y en los estados de Río Grande do Sul, Mato Grosso, Paraná y São Paulo, sobre las garantías jurídicas de las mujeres presas y sus hijos. El estudio pretende instrumentalizar una actuación garantista de los agentes públicos y dar visibilidad a esta problemática, frente a la extrema vulnerabilidad e invisibilidad jurídica y administrativa existente. Se identificaron 33 normas legales, con puntos de tensión, como la posibilidad de arresto domiciliario y disparidades en cuanto a los términos y condiciones de la estancia de los niños en el sistema penitenciario. La garantía constitucional del derecho a la lactancia materna se refleja en las regulaciones identificadas. No obstante, hay ausencias de otros aspectos de la maternidad en la cárcel, que se traduce en una doble pena para las mujeres, extendida arbitrariamente a sus hijos. Es necesaria la ampliación y ejecución efectiva de las regulación existente para prevenir y frenar las violaciones de los derechos.

Effects of High-dose Atorvastatin Pretreatment in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Cardiac Magnetic Resonance Study

It is uncertain that atorvastatin pretreatment can reduce myocardial damage in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the effects of atorvastatin pretreatment on infarct size measured by contrast-enhanced magnetic resonance imaging (CE-MRI) in STEMI patients. Patients undergoing primary PCI for STEMI within 12 hr after symptom onset were randomized to an atorvastatin group (n = 30, 80 mg before PCI and for 5 days after PCI) or a control group (n = 37, 10 mg daily after PCI). The primary end point was infarct size evaluated as the volume of delayed hyperenhancement by CE-MRI within 14 days after the index event. The median infarct size was 19% (IQR 11.1%-31.4%) in the atorvastatin group vs. 16.3% (7.2%-27.2%) in the control group (P = 0.27). The myocardial salvage index (37.1% [26.9%-58.7%] vs. 46.9% [39.9-52.4], P = 0.46) and area of microvascular obstruction (1.1% [0%-2.0%] vs. 0.7% [0%-1.8%], P = 0.37) did not differ significantly between the groups. Frequency of the hemorrhagic and transmural infarctions was not significantly different in the 2 groups. Pretreatment with a high-dose atorvastatin followed by further treatment for 5 days in STEMI patients undergoing primary PCI failed to reduce the extent of myocardial damage or improve myocardial salvage.

Anticorpos monoclonais anti PCSK9 / Anti-PCSK9 monoclonal antibodies

Inibição da PCSK9 constitui um dos mais promissores avanços para o tratamento da hipercolesterolemia nos últimos anos. Esta pró-proteína convertase ao interagir com a LDL e seu receptor hepático determina a degradação do receptor. Por meio de anticorpos monoclonais, esta ação é inibida na corrente circulatória e, desta forma, o receptor após captar a LDL pode ser reciclado muitas vezes, permitindo eficiente redução do LDL-colesterol. Estes fármacos se mostraram surpreendentemente bem tolerados, com perfil de segurança similar ao placebo e produziram reduções no LDL-C ao redorde 60%, independentemente de terapia prévia com outros hipolipemiantes como estatinas ou ezetimiba. Além disso,reduzem também a lipoproteína Lp (a), uma ação que não se observa com as estatinas. Estudos prospectivos destinado sao exame do impacto em desfechos cardiovasculares estão atualmente em curso e poderão ampliar as indicações hoje previstas, como seu uso para hipercolesterolemias primárias graves ou intolerância a estatinas.

Inhibition of PCSK9 constitutes one of the most promising advances for the treatment of hypercholesterolemia in thelast years. This proprotein convertase interacts with LDLand its receptor determining degradation of the receptor.Through the use of monoclonal antibodies, this effectis inhibited in the bloodstream, and thus, after the LDL capture, the receptor can be recycled many times, promotingan effective LDL-C decrease. Surprisingly, these drugsshowed safety profile similar to placebo and were very well tolerated, achieving LDL-C lowering around 60%, beyond previous therapies with statins or ezetimibe. In addition, these drugs also decrease lipoprotein Lp (a), an effect not observed with statins. Prospective studies aimedto evaluate the impact of treatment on cardiovascular eventsare currently ongoing and they may increase the possible indications recognized today, such as severe primary hypercholesterolemias or statin intolerance.

Oligonucleotídeos antisense para hipercolesterolemia e hipertrigliceridemia / Antisense oligonucleotide for hypercholesterolemia and hypertrigliceridemi

A hipercolesterolemia representa um dos principais fatores de risco para doença cardiovascular. Atualmente, as estatinas constituem a principal terapia farmacológica para seu tratamento. Contudo, existe um nicho de pacientes quemotivaram a busca por novas terapias hipolipemiantes: os intolerantes a estatinas e os pacientes com dislipidemias genéticas graves, sendo esse último grupo representado principalmente pela hipercolesterolemia familiar. Os oligonucleotídeos antisense são pequenas sequências de ácido nucleico de fita única que se ligam via hibridização de Watson-Crick no seu RNA complementar, levando à inibição da síntese da proteína que seria codificada por essa região do RNA. Atualmente, essa tecnologia está sendo utilizada para tratamento de diferentes doenças, inclusive das dislipidemias. A inibição da síntese da apolipoproteínaB com uso de oligonucleotídeo antisense (mipomersen) é uma realidade hoje em dia. Seu efeito se traduz na redução significativa do LDL-colesterol. O mipomersen faz parte do arsenal terapêutico aprovado pelo FDA para tratamento da hipercolesterolemia familiar homozigótica. Outras regiões proteicas das lipoproteínas, como apolipoproteína CIII e apolipoproteína(a), também são alvos de oligonucleotídeos antisense e podem representar novas medicações no combate a doença cardiovascular.

Hypercholesterolemia is a major risk factor for cardiovascular disease. Currently statins are the main pharmacological therapy for its treatment. However, there is a subgroup of patients who motivated the search for new lipid-lowering therapies: intolerant to statins and patients with severe genetic dyslipidemias, this last group represented primarily by familial hypercholesterolemia. Antisense oligonucleotides are short sequences of single-stranded nucleic acids which bind via Watson-Crick hybridization to its complementary RNA, leading to protein synthesis inhibition that would be encoded by this region of RNA.Currently this technology is used to treat various diseases including dyslipidemias. The inhibition of synthesis of apolipoprotein B with use of antisense oligonucleotide (mipomersen) is a reality today. Its effect is reflected insignificant reduction of LDL-cholesterol. The mipomersenis a medication approved by FDA for treatment of homozygous familial hypercholesterolemia. Other protein regions of lipoproteins such as apolipoprotein CIII and apolipoprotein(a) are also targets of antisense oligonucleotides and may represent new medications to reduce cardiovascular disease.

Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits / O Efeito da Pitavastatina na Reatividade Vascular em Coelhos Hipercolesterolêmicos

Background: Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective: To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods: Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results: Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion: Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits. .

Fundamento: A pitavastatina é a mais nova estatina disponível no Brasil e com prováveis menores efeitos colaterais. Assim, a pitavastatina foi avaliada em coelhos hipercolesterolêmicos em relação à ação na reatividade vascular. Objetivo: Investigar a menor dose de pitavastatina na redução dos lípides plasmáticos, colesterol e peroxidação lipídica tecidual e função endotelial em coelhos hipercolesterolêmicos. Métodos: Trinta coelhos divididos em seis grupos (n=5): G1 - dieta ração padrão; G2 - dieta hipercolesterolêmica por 30 dias; G3 - dieta hipercolesterolêmica e a partir do 16º dia suplementada com pitavastatina (0,1 mg); G4 - dieta hipercolesterolêmica e suplementada com pitavastatina (0.25 mg); G5 - dieta hipercolesterolêmica e suplementada com pitavastatina (0,5 mg); G6 - dieta hipercolesterolêmica e suplementada com pitavastatina (1,0 mg). Após 30 dias foram dosados o colesterol total, HDL, triglicérides, glicose, creatinoquinase, aspartato aminotransferase, alanina aminotransferase e o LDL calculado. Aprofundada a anestesia com tiopental sódico e retirado segmentos de aorta para estudo da função endotelial, colesterol e peroxidação lipídica tecidual. O nível de significância adotado para os testes estatísticos foi 5%. Resultados: Colesterol total e LDL elevados significativamente em relação ao G1. HDL reduzida significativamente em G4, G5 e G6 em relação ao G2. Triglicérides, creatinoquinase, aspartato aminotransferase, alanina aminotransferase, colesterol e peroxidação lipídica tecidual sem diferença estatística entre G3-G6 e G2. Disfunção endotelial revertida significativamente em G5 e G6 em relação ao G2. Conclusão: A pitavastatina, a partir da ...