Prescription of statins according to the ASCVD estimator at Pablo Arturo Suarez Hospital, March 2021 to February 2022 / Prescripción de estatinas según el estimador ASCVD en el Hospital Pablo Arturo Suárez, marzo 2021 a febrero 2022

Worldwide, the leading cause of death is cardiovascular disease. The study details the prescription of statins at the Pablo Arturo Suarez Hospital in Ecuador between March 2021 and February 2022 following the ASCVD risk scale of the American College of Cardiology and the American Heart Association. There are 563 people in this cross-sectional and retrospective study: 70% women, 30% men, 93.30% mestizos, 48.10% diabetics, 62.30% hypertensives, and 18.70% smokers. 26.10% of all patients received statins, with simvastatin being the most common (96.60%). The mean cardiovascular risk in the general population was 15.52 ± 14.51%, 44.99% of subjects had a risk lower than 7.50%, and 29% had a risk higher than 20%, with a statistically significant difference (p<0.001) according to sex. The study determined that 58.60% of the population received a statin or an inadequate dosage.

A nivel mundial, la principal causa de muerte es la enfermedad cardiovascular. El estudio detalla la prescripción de estatinas en el Hospital Pablo Arturo Suárez de Ecuador entre marzo de 2021 y febrero de 2022, siguiendo la escala de riesgo ASCVD del Colegio Americano de Cardiología y la Asociación Americana del Corazón. Son 563 personas en este estudio transversal y retrospectivo: 70% mujeres, 30% hombres, 93.30% mestizos, 48.10% diabéticos, 62.30% hipertensos y 18.70% fumadores. El 26.10% de los pacientes recibía estatinas, siendo la simvastatina la más frecuente (96.60%). El riesgo cardiovascular medio en la población general fue de 15.52 ± 14.51%, el 44.99% de los sujetos tenía un riesgo inferior al 7.50%, y el 29% tenía un riesgo superior al 20%, con una diferencia estadísticamente significativa (p<0.001) según el sexo. El estudio determinó que el 58.60% de la población recibía una estatina o una dosis inadecuada.

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)

Posicionamento de cabo-eletrodo de ventrículo esquerdo na ressincronização cardíaca guiado pela cintilografia miocárdica gated-SPECT* / Positioning of left ventricular lead in cardiac resynchronization guided by gated-SPECT myocardial scintigraphy

A terapia de ressincronização cardíaca representa importante modalidade terapêutica, principalmente para pacientes com insuficiência cardíaca e distúrbios de condução pelo ramo esquerdo. No entanto, a resposta a essa terapia é heterogênea, em virtude dos vários fatores que implicam a dissincronia eletromecânica. O presente relato aborda um caso de sucesso com super-resposta à terapia de ressincronização, na qual o cabo-eletrodo de ventrículo esquerdo foi posicionado de acordo com o sítio de maior retardo determinado pela cintilografia miocárdica com análise de fase gated-SPECT

Cardiac resynchronization therapy represents an important therapeutic modality mainly for patients with heart failure and left bundle branch conduction disorders. However, the response to this therapy is heterogeneous because of the various factors involved in electromechanical dyssynchrony. The present report addresses a successful case with super-response to resynchronization therapy in which the left ventricle electrode was positioned according to the site of greatest delay determined by myocardial scintigraphy with gated-SPECT phase analysis

Differential therapeutic effects of Crataegus aronia and simvastatin on the hepatocyte ultrastructure in hepatic steatosis / Efectos terapéuticos diferenciales de Crataegus aronia y simvastatina sobre la estructura del hepatocito en la esteatosis hepática

Complications of fat accumulation in liver, hepatic steatosis such as liver cirrhosis and liver failure are among the common public health problems. We sought to investigate the damage to the hepatocyte ultrastructure induced by high fat diets (HFD) and compared the therapeutic effects at the cellular level of two antioxidant and lipid lowering agents; Crataegus aronia extracts and simvastatin on hepatic steatosis. Rats were either fed with HFD (model group) or low fat diets (LFD) (control group) for 15 weeks before being sacrificed and therapeutic groups started the treatment with these agents after week 11 until the sacrifice day. Harvested liver tissues were examined using transmission electron microscopy (TEM) and liver homogenates were assayed for markers of anti-oxidative stress that are known to be modulated in liver injury. TEM examinations of the model group showed a profound damage to the hepatocytes compared to the control group as demonstrated by steatosis, damaged mitochondria and vaculated cytoplasm, disrupted rough and smooth endoplasmic reticulum and nuclear membrane, dilated intercellular space between hepatocytes, and alterations in lysosomes. In addition, HFD ameliorated the anti-oxidant glutathione (GSH) and augmented the oxidative stress TBARS biomarkers. Both Crataegus aronia and simvastatin significantly reduced lipids and TBARS, and treated damage to hepatic cells, but hepatocyte structures were differentially responded to these agents. However, only Crataegus aronia induced GSH (p=0.001). We conclude that HFD-induced hepatic steatosis caused a substantial damage to the hepatocyte's ultrastructures, and Crataegus aronia and simvastatin treatments differentially reversed hepatic injuries.

Las complicaciones de la acumulación de grasa en el hígado, la esteatosis hepática como la cirrosis hepática y la insuficiencia hepática se encuentran entre los problemas comunes de salud pública. Se intentó investigar el daño a la ultraestructura de los hepatocitos inducido por la dieta alta en grasas (DAG) y se compararon los efectos terapéuticos a nivel celular de dos antioxidantes y agentes hipolipemiantes; Extracto de Crataegus aronia y simvastatina sobre esteatosis hepática. Las ratas fueron alimentadas con DAG (grupo modelo) o dieta baja en grasa (DBG) (grupo control) durante 15 semanas antes de sacrificarse y los grupos terapéuticos comenzaron el tratamiento con estos agentes después de la semana 11 hasta el día del sacrificio. Se examinaron los tejidos hepáticos usando microscopía electrónica de transmisión (MET) y se analizaron homogeneizados de hígado para marcadores de estrés anti-oxidativo, que se sabe están modulados en la lesión hepática. Los exámenes MET del grupo DAG mostraron un grave daño de los hepatocitos en comparación con el grupo control, demostrado por esteatosis, daño mitocondrial y citoplasma vacío, retículo endoplásmico rugoso y liso y membrana nuclear, el espacio intercelular dilatado entre hepatocitos y alteraciones en los lisosomas. Además, DAG mejoró el anti-oxidante glutatión (GSH) y aumentó el estrés oxidativo TBARS biomarcadores. Tanto Crataegus aronia como simvastatina redujeron significativamente los lípidos y TBARS, trataron el daño a las células hepáticas, pero las estructuras de hepatocitos respondieron diferencialmente a estos agentes. Sin embargo, sólo Crataegus aronia indujo GSH (p = 0,001). Concluimos que la esteatosis hepática inducida por HFD causó un daño sustancial a la ultraestructura del hepatocito y los tratamientos de Crataegus aronia y simvastatina diferenciaron las lesiones hepáticas.

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

ABSTRACT Membrane/lipid rafts (MLRs) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (statins) can disable the N-methyl-D-aspartate (NMDA) receptor through disruption of MLRs and, in turn, decrease NMDA-mediated anxiety. This hypothesis will contribute to understanding the critical roles of simvastatin in treating anxiety via the NMDA receptor.

Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice

Functional food intake has been highlighted as a strategy for the prevention of cardiovascular diseases by reducing risk factors. In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr-/-) fed a hyperlipidic diet. Forty 3-month old male LDLr-/- mice were distributed into four groups: control group (C), in which animals received standard diet; HL group, in which animals were fed a hyperlipidic diet; HL+SM or HL+S groups, in which animals were submitted to a hyperlipidic diet plus soy milk or simvastatin, respectively. After 60 days, both soy milk and simvastatin treatment prevented dyslipidemia, atherosclerotic lesion progression and left ventricle hypertrophy in LDLr-/- mice. These beneficial effects of soy milk and simvastatin were associated with reduced oxidative stress and inflammatory state in the heart and aorta caused by the hyperlipidic diet. Treatment with soy milk was more effective in preventing HDLc reduction and triacylglycerol and VLDLc increase. On the other hand, simvastatin was more effective in preventing an increase in total cholesterol, LDLc and superoxide production in aorta, as well as CD40L both in aorta and left ventricle of LDLr-/-. In conclusion, our results suggest a cardioprotective effect of soy milk in LDLr-/- mice comparable to the well-known effects of simvastatin.

Effects of cococonut water and simvastatin in the treatment of sepsis and hemorrhagic shock in rats

ABSTRACT PURPOSE: To evaluate the effects of modified coconut water as fluid of resuscitation combined with simvastatin in hemorrhagic shock and sepsis model in rats. METHODS: Four groups of Wistar rats with hemorrhagic shock and abdominal sepsis were studied (n=8/group). Rats were bled and maintained at a mean blood pressure 35mmHg for 60min. They were then resuscitated with: 1) saline 0.9%; 2) coconut water+3% NaCl; 3) coconut water+NaCl 3%+simvastatin microemulsion (10 mg/kg i.v.; 4) normal coconut water. At 8h post-resuscitation, blood and lungs were collected for exams. RESULTS: Clinical scores, TNF-α, IL-1β, liver/kidney proof levels, and lung injury were significantly reduced in coconut water+NaCl 3%+simvastatin group treated rats, comparing with the other resuscitation treatments. CONCLUSIONS: Resuscitation with coconut water with Nacl 3%+simvastatin had a significant beneficial effect on downregulating cytokines and decreasing lung injury in a rat model of abdominal sepsis and hemorrhagic shock. We also demonstrated that coconut water with Nacl 3%+simvastatin administration clearly made liver and kidney function better and improved clinical score.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe / Efeito Endotelial da Terapia com Estatina em Alta Dose versus Baixa Dose Associada à Ezetimiba

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Resumo Fundamento: O efeito das estatinas na função endotelial em seres humanos permanece em discussão. Particularmente, ainda carece resposta se a melhora na função endotelial deve-se à redução do LDL-colesterol ou a um efeito pleiotrópico arterial. Objetivo: Testar a hipótese de que a modulação da função endotelial promovida por estatinas é prioritariamente mediada pelo grau de redução do LDL-colesterol, independente da dose de estatina utilizada. Métodos: Ensaio clínico randomizado com dois grupos de tratamento hipolipemiante (16 pacientes/cada) e um grupo placebo (14 pacientes). Os dois grupos ativos foram desenhados para promover graus semelhantes de redução de LDL-colesterol: o primeiro utilizou estatina em alta dose (80 mg, grupo sinvastatina 80) e o segundo em baixa dose (10 mg) associada a ezetimiba (10 mg, grupo sinvastatina 10/ezetimiba) para otimizar o efeito hipolipemiante. A função endotelial foi analisada pela vasodilatação mediada por fluxo (VMF) antes e após 8 semanas de tratamento. Resultados: A redução no LDL-colesterol foi semelhante entre os grupos sinvastatina 80 e sinvastatina 10/ezetimiba (27% ± 31% e 30% ± 29%, respectivamente, p = 0,75). O grupo sinvastatina 80 apresentou incremento da VMF de 8,4% ± 4,3% no basal para 11% ± 4,2% após 8 semanas (p = 0,02). Da mesma forma, o grupo sinvastatina 10/ezetimiba apresentou melhora da VMF de 7,3% ± 3,9% para 12% ± 4,4% (p = 0,001). O grupo placebo não apresentou variação no nível de LDL-colesterol ou da função endotelial. Conclusão: A melhora da função endotelial com uso de estatina parece depender mais da redução do LDL-colesterol, independente da dose de estatina utilizada, do que de mecanismos pleiotrópicos.

Avaliação do impacto das novas diretrizes no uso de estatinas / Assessing the impact of new guidelines on the use of statins

Fundamentos: A doença arterial coronariana é a principal causa de morte no Brasil e possui relação direta com a dislipidemia. Objetivo: Analisar o padrão do uso de estatinas antes e após a publicação das novas diretrizes de dislipidemia em pacientes com doença cardiovascular aterosclerótica prévia. Métodos: Estudo transversal, retrospectivo. Foram avaliados, aleatoriamente, 515 pacientes consecutivos com doença aterosclerótica, atendidos no ambulatório do Instituto de Cardiologia de Santa Catarina, SC, Brasil , entre2011 e 2015. Destes, apenas 76,9% faziam uso de alguma estatina. Foram coletados dados de história clínica, fatores de risco para doença cardiovascular, dados laboratoriais referentes aos valores de colesterol (HDL-c e LDL-c) e triglicerídeos (TG), tratamento referente à escolha das estatinas e suas doses, antes e depois de outubro de 2013,data de publicação das novas diretrizes. Resultados: Após a publicação das novas diretrizes, 477 pacientes utilizavam estatinas, representando 92,6% da amostra avaliada (p=0,0001). Quanto à escolha da estatina, o uso de sinvastatina diminuiu para 69,2% (p=0,02),o de atorvastatina aumentou para 25,2% (p=0,003) e o de rosuvastatina foi 5,7% (p=ns). Antes da divulgação das novas diretrizes, as doses médias de sinvastatina, atorvastatina e rosuvastatina eram 33,6±9,4mg, 32,1±18,9mg,13,1±7,9mg, respectivamente. Após a publicação, essas doses médias aumentaram para: sinvastatina 36,7±7,9mg(p=0,0001) e atorvastatina 36,8±16,2mg (p=0,0001). Conclusões: As taxas de uso de estatinas na amostra estudada aumentaram após a publicação da nova Diretriz ACC/AHA e da V Diretriz brasileira de dislipidemia, no entanto atingiu um número limitado de pacientes, associado a doses abaixo do preconizado e metas numéricas inadequadas de colesterol, o que pode gerar implicações prognósticas desfavoráveis.

Background: Coronary artery disease (CAD) is the leading cause of death in Brazil and has a direct connection with dyslipidemia. Objective: To analyze the pattern of use of statins before and after the publication of the new guidelines on dyslipidemia in patients with a history of atherosclerotic cardiovascular disease. Methods: Cross-sectional retrospective study. In this study, 515 consecutive patients with atherosclerotic were randomly evaluatedat the outpatient facility of Instituto de Cardiologia de Santa Catarina, SC, Brazil, between 2011 and 2015. Of these, only 76.9%were using statins. Data relating to clinical history, risk factors for cardiovascular disease, laboratory data for cholesterol levels (HDL-c and LDL-c) and triglycerides (TG) were collected, as well as treatment concerning the choice of statins and their doses before and after October 2013, when the new guidelines were published. Results: After the publication of the new guidelines, 477 patients used statins, representing 92.6% of the study sample (p=0.0001). As to the choice of statin, the use of simvastatin declined to 69.2% (p=0.02), atorvastatin increased to 25.2% (p=0.003) and rosuvastatin was 5.7% (p=ns). Before the release of the new guidelines, the average doses of simvastatin, atorvastatin and rosuvastatin were 33.6±9.4mg, 32.1±18.9mg, 13.1±7.9mg, respectively. After publication, these average doses increased to: simvastatin 36.7±7.9mg (p=0.0001) and atorvastatin 36.8±16.2mg (p=0.0001). Conclusions: The statin use rates in the study sample increased after the publication of the new ACC/AHA Guidelines and theV Brazilian Guidelines on Dyslipidemia. However, they reached a limited number of patients, associated with doses below there commended and improper numerical targets of cholesterol, which can generate unfavorable prognostic implications.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System / Efetividade de Estatinas em Dose Alta, Moderada e Baixa na Prevenção de Eventos Vasculares no SUS

Background: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. Objective: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective. Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied. Results: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. Conclusions: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil. .

Fundamento: Estatinas tem eficácia comprovada na redução de eventos cardiovasculares, mas o impacto financeiro de seu uso disseminado pode ser substancial. Objetivo: Conduzir análise de custo-efetividade de três esquemas de doses de estatinas na perspectiva do SUS. Métodos: Foi desenvolvido modelo de Markov para avaliar a razão de custo-efetividade incremental (RCEI) de regimes de dose baixa, intermediária e alta, em prevenção secundária e quatro cenários de prevenção primária (risco em 10 anos de 5%, 10%, 15% e 20%). Regimes com redução de LDL abaixo de 30% (ex: sinvastatina 10mg) foram considerados dose baixa; entre 30-40% (atorvastatina 10mg, sinvastatina 40mg), dose intermediária; e acima de 40% (atorvastatina 20-80 mg, rosuvastatina 20 mg), dose alta. Dados de efetividade foram obtidos de revisão sistemática com aproximadamente 136.000 pacientes. Dados nacionais foram usados para estimar utilidades e custos (expressos em dólares internacionais - Int$). Um limiar de disposição a pagar (LDP) igual ao produto interno bruto per capita nacional (aproximadamente Int$11.770) foi utilizado. Resultados: A dose baixa foi dominada por extensão nos cenários de prevenção primária. Nos cinco cenários, a RCEI da dose intermediária ficou abaixo de Int$10.000 por QALY. A RCEI de dose alta ficou acima de Int$27.000 por QALY em todos os cenários. Nas curvas de aceitabilidade de custo-efetividade, dose intermediária teve probabilidade de ser custo-efetiva acima de 50% com RCEIs entre Int$9.000-20.000 por QALY em todos os cenários. Conclusões: Considerando um LDP razoável, uso de estatinas em doses intermediárias é economicamente atrativo, e deveria ser intervenção prioritária na redução de eventos cardiovasculares no Brasil. .

Avaliação da qualidade e equivalência farmacêutica de comprimidos contendo 10mg de sinvastatina / Assessment of quality and pharmaceutical equivalence of 10 mg simvastatin tablets

A sinvastatina, pertencente à classe das estatinas, é um importante fármaco redutor do colesterol e é encontrada comercialmente como medicamentos referência, genéricos e similares em diferentes dosagens, sendo a de 10 mg a mais comum. Este trabalho tem como objetivo avaliar a qualidade e a equivalência entre comprimidos de sinvastatina 10 mg comercializados no mercado brasileiro. Foram selecionados dois medicamentos similares, um genérico e referência. Os ensaios de controle de qualidade aplicados foram: determinação do peso médio, dureza, friabilidade, desintegração, teor de princípio ativo, uniformidade de conteúdo e dissolução in vitro. Para tanto, foi necessário desenvolvimento e validação de metodologia por espectrofotometria na região do ultravioleta (UV). As formulações apresentaram-se dentro dos limites preconizados para todas as análises. No entanto, quando analisou-se estatisticamente os perfis de dissolução, verificou-se a não equivalência entre os medicamentos similares e o de referência. Porém, através dos resultados obtidos, podemos evidenciar a equivalência entre o genérico e o de referência, sugerindo sua intercambialidade...

Simvastatin, a well-known medicine of the statin class, is used therapeutically for the reduction of cholesterol and is commercially available in reference, similar and generic forms, in various doses, the tablet of 10 mg being the commonest in prescriptions. The purpose of this study was to test the quality and the pharmaceutical equivalence of tablets containing 10 mg of simvastatin available on the Brazilian market. One generic, one reference and two similar dosage forms were selected. The quality-control variables used were: weight variation, hardness, friability, disintegration, content of the active principle, content uniformity and dissolution in vitro. A UV-spectrophotometric method was developed and validated. All formulations were approved in the quality analysis. By using mathematical and statistical models, it was observed that the dissolution profiles of the similar dosage forms were not equivalent to that of the reference. On the other hand, when the generic medicine was compared with the reference, their interchangeability was confirmed...

Papel das estatinas na modulação da função endotelial vasomotora na hipertensão e doença coronariana / The role of statins in the modulation of endothelium vasomotor function in hypertension and coronary artery disease

o benefício em longo prazo do tratamento com estatinas naprevenção de eventos coronarianos primários e secundários éindiscutível. Embora uma parte deste benefício esteja ligadaao efeito sobre a redução da circulação de lipoproteínasaterogênicas, outros mecanismos, como a modulação datrombogênese, a redução da inflamação e melhora da funçãoendotelial, têm sido investigados. O efeito da estatina sobrea função endotelial está ligado à sua inibição da produçãode superóxido e sua regulação positiva da síntese do óxidonítrico (NOS) no endotélio. Na prática clínica, o benefíciona função do endotélio depois do tratamento com estatinatem sido observado em uma ampla variedade de condiçõesque incluem a hipertensão arterial sistêmica, doença arterialcrônica e síndrome coronariana aguda. Esta breve revisãoincidirá sobre as principais conclusões relacionadas à terapiacom estatina sobre o tônus arterial sistêmico e doença arterialcoronariana aguda e crônica...

The long-term benefit of statin treatment on the prevention of primary and secondary coronary events is undisputed. Although a proportion of this effect has been linked to its reduction of circulating atherogenic lipoproteins, other mechanisms have been studied such as modulation of thrombogenesis, reduction of inflammation, and improvement of endothelia! function. Its favorable effect on endothelial function is tied to its inhibition of superoxide production and its positive regulation of nitric oxide synthase (NOS) in the endothelium. In the clinica! setting, the gain in endothelia! function after statin treatment has been observed in a wide range of conditions that include systernic hypertension, chronic arterial disease, and acute coronary syndrome. This brief review will focus on the main findings related to statin therapy on the systernic arterial tone and both acute and chronic coronary artery disease...

Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Avanços nos materiais e no tratamento endovascular de oclusões arteriais crônicas totais: um relato de caso / Advances in materials and endovascular treatment of chronic total arterial occlusions: a case report

As oclusões arteriais crônicas totais com forte componente cálcico são ainda nos dias atuais, um fator muitas vezes limitante para o tratamento endovascular devido à dificuldade em transpor estas lesões com fios-guia e cateteres habitualmente utilizados. Revisamos a literatura e descrevemos um caso de tratamento endovascular de uma oclusão total de artéria ilíaca externa, onde o uso de novos materiais desenvolvidos especificamente para o tratamento deste tipo de lesão foi determinante para o sucesso do caso.

Chronic arterial occlusions with great calcium component are usually a factor of limitation to endovascular treatment to the difficulty to transpose these lesions with guidewires and catheters commonly used. We reviewed the literature and described a case of endovascular treatment of a total occlusion of external iliac artery, where the use of new materials developed specifically to the treatment of such injuries was critical to the success of the case.

Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.

Relação entre sinvastatina e diferenciação celular da polpa humana dentária / The relationship between sinvastatin and cell differentiation of human dental pup

Nosso organismo é formado a partir de células que se multiplicam e se diferenciam. essas células são chamadas de "stemcells". No tecido dental, podemos observar intensa atividade diferencial em relação à dentina, que tem, como uma de suas funções, a proteção tecido pulpar. Frente a uma injúria (atrição, cárie ou procedimento restaurador), os odontoblastos são estimulados à deposição de dentina. Estudos mostram que materiais como hidróxido de cálcio PA, o cimento de hidróxido de cálcio, o agregado trióxido mineral (MTA) e, mais recetemente, a Sinvastatina são capazes de induzir a estimulação dos odontoblastos, quando em contato direto ou indireto com o tecido pulpar. este trabalho teve como objetivo discorrer, por meio da revisão de literatura, sobre a ação da Sinvastatina e sua relação com o diferencial celular da polpa dental humana, destacando suas implicações odontológicas. assim, pudemos concluir que a Sinvastatina é uma importatnte aliada na regeneração do tecido pulpar, por meio de sua ação anti-inflamatória; promove indução da diferenciação celular, pelo contato com o tecio pulpar, no capeamento pulpar direto ou indireto. Estudos adicionais são necessários para estabelecer a Sinvastatina como medicação para o capeamento pulpar; os métodos existentes promovem ação desejada para esses casos, já comprovada por experiência clínica e estudos. Deve-se avaliar se há vantagem na utilização da Sinvastatina quanto ao custo/benefício, em relação aos medicamentos já utilizados.

The human body is formed from cells that multiply and differentiate theselves. These cells are called "stem cells". In dental tissue, we can observe an intensive differential activity over the dentin, with has pulp tissue protection as one of its functions. Faced withan injury (atrition, caries or restorative procedure), the odontoblast are stimulated at the deposition of dentin. Studies show that materials such as calcium hydroxide cement, the mineral trioxide aggregate (MTA) and, more recently, the Sinvastatin are capable of inducing the stimulation of odontoblasts, when they are in direct or indirect contact with the pulp tissue. This study aimed to discuss, through a literature review on the effect os Sinvastatin and its relationship with tbe cell differentiation of human dental pulp, specially its dental implications. Thus, we concluded that Sinvastatin is an important ally in the regeneration of the of the pulp tissue, through its anti-inflammatory activity; promotes the induction of cell differentiation, through the contact with pulp tissue, in direct or indirect pulp capping; addiotional studies are needed to establish Sinvastatin as medication for pulp capping; the existing methods promote the desired action for these cases, provent by clinical experiences an studies; an assessment must be made in order to find out wether there is an advantage in using Sinvastatin as the cost/benefit in relation to products that have already been used.

Fatal Rhabdomyolysis in a Patient with Liver Cirrhosis after Switching from Simvastatin to Fluvastatin

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.

Effects of Combined Therapy with Ezetimibe Plus Simvastatin After Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.

Muscle response to the association of statin and physical exercise in rats / Respuestas musculares de la asociación de estatina y ejercicio físico aeróbico en ratas

Physical exercise and statins, which are recommended for the treatment of dyslipidemia, are independently associated to the occurrence of muscle injury. The objective is analyze the effect of aerobic exercise associated to the use of simvastatin on the morphology of the gastrocnemius muscle. Thirty Wistar rats were divided into six groups, two of which received a standard diet (1 sedentary and 1 exercised) and four (1 sedentary with medication, 1 sedentary without medication, 1 exercised with medication, 1 exercised without medication) received a hypercholesterolemic diet (standard diet with the addition of cholesterol and coconut oil). Simvastatin (20 mg/Kg) was administered five days a week for eight weeks, together with aerobic training on a treadmill (9.75 m/min) for 60 minutes a day. The gastrocnemius muscle was removed, sliced, stained with Hematoxylin-Eosin and submitted to a histochemical reaction to determine mitochondrial activity. The data were analyzed using a paired t-test, analysis of variance and Scheffé's post hoc test (p<0.05). Greater histological alterations were found in the medicated and exercised animals, with a greater frequency of occurrence as well. The histochemical analysis revealed that the medicated groups had fibers with more intensive mitochondrial activity alongside fibers with an absence of reaction. The morphometric analysis revealed no significant differences between groups. It is suggested that simvastatin is a medication that leads to the occurrence of muscle injury and its administration in association with physical activity may exacerbate these injuries. This finding may be related to cellular respiration.

El ejercicio físico y las estatinas, son intervenciones recomendadas para el tratamiento de la dislipidemia y están independientemente asociadas con la ocurrencia de lesiones musculares. El objetivo fue analizar el efecto del ejercicio aeróbico asociado al uso de la sinvastatina en la morfología del músculo gastrocnemio. 30 ratas macho Wistar fueron divididos en 6 grupos, de los cuales 2 recibieron ración padrón, sedentarios, ejercitados y 4 recibieron dieta con alto nivel de colesterol, sedentarios con y sin medicamento, ejercitados con y sin medicamentos. La dieta fue elaborada a partir de una dieta padrón aumentada de colesterol y aceite de coco. La Sinvastatina (20 mg) fue administrada por 5 días por semana durante 8 semanas (20 mg/kg), junto al entrenamiento aeróbico en la estera (9,75 m/min) por 60 minutos por día. El músculo gastrocnemio colectado fue cortado y colorido por el método Hematoxilina-Eosina y sometido a una reacción histoquímica para verificar la actividad mitocondrial. Los datos fueron analizados utilizando el test t pareado, análisis de la variancia e Pos-Hoc de Scheffé, adoptándose p<0,05. Se verifico la presencia de alteraciones histológicas más significativas en los animales medicados y ejercitados, siendo también mayor la frecuencia de ocurrencia. El análisis histoquímica apunto que los grupos medicados presentaron fibras con actividad mitocondrial más intensa, al lado de fibras con pérdida de reacción. Los resultados de la morfometría no mostraron diferencias significativas entre los grupos estudiados. Se puede sugerir que la simvastatina es un medicamento que lleva a la ocurrencia de lesiones musculares e que su administración concomitante con la práctica de actividad física puede exacerbar estas lesiones, pudiendo tal hecho, estar relacionado con la respiración celular.