Treatment of mild-to-moderate hypertriglyceridemia. / Tratamiento de la hipertrigliceridemia leve-moderada.

The atherogenic role of triglycerides (TG) as an independent cardiovascular risk factor has been discussed for many years, largely because hypertriglyceridaemia (HTG) is a complex metabolic entity of multiple aetiology involving processes of diverse nature. In this chapter, a discussion will be presented on the current recommendations for the management of mild-moderate hypertriglyceridaemia (150-880mg/dL). The aim of the interventions used is to decrease the LDL-cholesterol (c-LDL) and control the HTG. This entails reducing apoprotein B (ApoB) levels, the number of remaining TG-rich lipoproteins (LRP), non-HDL-cholesterol (c-non-HDL), and increasing HDL-cholesterol (c-HDL). The management strategy includes healthy lifestyle recommendations, and subsequent use of lipid-lowering drugs, including statins, fibrates, n-3 fatty acids and PCSK9 inhibitors.

Control of the overall lipid profile. / Control del perfil lipídico global.

The importance of overall lipid control in cardiovascular prevention is reviewed. Several studies and meta-analyses show that the control of LDL cholesterol (LDL-C) still maintains a high cardiovascular risk, which is related to the presence of triglyceride-rich lipoproteins, and therefore with an increase in plasma triglycerides and the values of apolipoprotein B (apoB) containing these lipoproteins. The importance of this relationship is due to the change in the lipid profile of our population in recent years. This is related to the increase in obesity and insulin resistance, and is called atherogenic dyslipidaemia. Thus, hypertriglyceridaemia should be considered a cardiovascular risk factor, especially when the desirable objectives of LDL-C have been achieved. The indications for treatment with fibrates in primary and secondary prevention, using the medical evidence-based recommendations, are described, along with its importance in the reduction of cardiovascular risk. Finally, the established indications of the combined statin-fibrate treatment are presented, always after changes in lifestyle.

Simvastatin and other inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase of Ustilago maydis (Um-Hmgr) affect the viability of the fungus, its synthesis of sterols and mating.

BACKGROUND: The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgr) catalyzes the synthesis of mevalonate, a key compound for the synthesis of cholesterol in humans and ergosterol in fungi. Since the Hmgr enzymes of Saccharomyces cerevisiae, Schizosaccharomyces pombe and Candida glabrata are similar to the Hmgr enzymes of mammals, fungal Hmgr enzymes have been proposed as a model for studying antifungal agents. AIMS: To examine the correlation between inhibiting Um-Hmgr enzyme and the viability, sterols synthesis and mating in Ustilago maydis. METHODS: Using in silico analysis, the ORF codifying for Um-Hmgr was identified and the protein characteristics were deduced. The effect of the competitive inhibitors of Um-Hmgr on the viability of this basidiomycota, the synthesis of its sterols, and its mating were evaluated. RESULTS: The Umhmgr gene (XP_011389590.1) identified putatively codifies a protein of 1443 aa (ca. MW=145.5kDa) that has a possible binding domain in the endoplasmic reticulum (ER) and high identity with the Hmgr catalytic domain of humans and other yeasts. The inhibition of Um-Hmgr caused a decrease of viability and synthesis of sterols, and also the inhibition of mating. The activity of Um-Hmgr is mainly located in the membrane fraction of the fungus. CONCLUSIONS: Given our results we believe U. maydis is a valid model for studying synthetic inhibitors with lipid-lowering or antifungal activity. Additionally, we propose the Hmgr enzyme as an alternative molecular target to develop compounds for treating both phytopathogenic and pathogenic human fungi.

Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration. / Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane.

Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels.

Fibrates in the secondary prevention of cardiovascular disease (infarction and stroke). Results of a systematic review and meta-analysis of the Cochrane collaboration. / Los fibratos en la prevención secundaria de la enfermedad cardiovascular (infarto e ictus). Resultados de una revisión sistemática y metaanálisis de la colaboración Cochrane.

Fibrates are a group of drugs that are known mainly for reducing triglycerides, increasing high density lipoproteins (HDL), and reducing the fraction of small, dense LDL particles. The results of a Cochrane Collaboration study have recently been published on their efficacy and safety in the secondary prevention of severe cardiovascular accidents, including coronary and cerebrovascular disease. The study included randomised clinical trials in which the fibrate was compared with placebo or with no treatment. Clinical trials comparing two different fibrates were excluded. The clinical trials evaluated included a total of 16,112 patients (13 trials). The meta-analysis (including all the trials with fibrates) showed evidence of a protective effect of the fibrates compared with placebo as regards a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin (hazard ration of 0.88, with a 95% confidence interval of 0.83 to 0.94; in 16,064 individuals included in 12 studies). Thus, the results showed, with a moderate level of evidence, that fibrates could be effective in secondary prevention considering a compound objective of non-fatal stroke, non-fatal myocardial infarction, and death of cardiovascular origin.

Triglicéridos y riesgo cardiovascular / Triglycerides and cardiovascular risk

Resumen: La relación entre triglicéridos y riesgo cardiovascular ha dado lugar a un conflicto de información. Por un lado, se sugiere una fuerte asociación epidemiológica, pero por otro, existe carencia de pruebas generadas por la investigación clínica de que su reducción se asocie con disminución de eventos cardiovasculares. En este artículo se tratan de explicar las posibles razones fisiopatogénicas y metodológicas de esta controversia, se muestran datos recientes del análisis del riesgo que confieren las diferentes clases de dislipidemias encontradas en la clínica, y de probables beneficios del tratamiento con fibratos, así como recomendaciones prácticas de manejo de las dislipidemias asociadas con hipertrigliceridemia más comunes en nuestra población.

Abstract: The relationship between triglycerides and cardiovascular risk has led to an information conflict. On the one hand, a strong epidemiological association is suggested, but on the other hand there is a lack of evidence generated by clinical research that its reduction is associated with a decrease in cardiovascular events. In this article we try to explain the possible pathophysiological and methodological reasons for this controversy, we show recent data on the risk analysis of the different types of dyslipidemias found in the clinic, and the probable benefits of treatment with fibrates, as well as practical recommendations of management of the hypertriglyceridaemia-associated dyslipidemias most common in our population.

Dislipidemia aterogénica en Latino América: prevalencia, causas y tratamiento / Atherogenic dislipidemia in Latin America: prevalence, causes and treatment

En las guías clínicas actuales, la dislipidemia aterogénica (DA) es una entidad escasamente atendida. Debido a las frecuentes alteraciones en los lípidos asociados a la DA en Latino América (LA), se organizó un grupo de expertos que se ha denominado Academia Latino Americana para el estudio de los Lípidos (ALALIP) para generar un documento con análisis de su prevalencia y ofrecer recomendaciones prácticas. Se utilizó la metodología Delphi modificada, con revisión comprensiva de la literatura con énfasis en aquellas publicaciones con implicaciones para LA. Subsecuentemente, se desarrollaron preguntas claves para ser discutidas. En LA no existe un estudio global sobre los factores de riesgo que representan a la totalidad de la población. El análisis sistemático de las encuestas nacionales de salud y de los estudios sistemáticos de cohorte muestran consistentemente una alta prevalencia de las anormalidades lipídicas que definen la DA. La concentración baja del colesterol unido a las lipoproteínas de alta densidad (C-HDL) varía entre 34,1% a 53,3% y la de triglicéridos (TG) elevados del 25,5% al 31,2%, con mayor prevalencia entre los hombres. Múltiples causas se han reconocidos, como alta ingesta de alimentos de mayor densidad calórica, contenido de colesterol, grasas trans, sedentarismo y cambios epigenéticos. La DA bien puede ser tratada con los cambios terapéuticos del estilo de vida (CTEV) con incremento en la actividad física, ejercicio regular y dieta baja en carbohidratos y alta en ácidos grasos poliinsaturados, tales como los ácidos grasos omega-3 como intervención primaria. De ser necesario, esta estrategia sera suplementada con terapia farmacológica como la monoterapia con estatinas o la combinación de fibratos/ácidos grasos omega-3. Las anormalidades lipídicas que definen la DA tienen una elevada prevalencia en LA; su interacción con un estilo de vida no saludable, herencia y cambios epigenéticos están ligados a sus posibles causas. La DA es una causa importante de riesgo cardiovascular residual (RCVR) que debe ser diagnosticada y tratada. Es importante y necesario diseñar un estudio global de factores de riesgo en LA para conocer la real prevalencia de la DA.

In the current clinical guidelines, atherogenic dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named Latin American Academy for the study of Lipids (ALALIP), to generate a document for analyzing its prevalence and to offer practical recommendations. Using the Delphi methodology, we conducted a comprehensive literature review, with emphasis on those publications with implications for LA. Subsequently we developed key questions to be discussed. In LA there is no a global study on risk factors that represent the entire population. The systematic analysis of national health surveys and regional cohort studies showed a consistent high prevalence of the lipid abnormalities that define AD. Low high density lipoprotein cholesterol (HDL-C) ranges from 34.1% to 53.3% and elevated triglycerides (TG) from 25.5% to 31.2%, more prevalent in men. There are multiple causes: high consumption of foods with a high caloric density, cholesterol and trans fats, sedentary lifestyle and epigenetic changes. AD must be well treated with therapeutic changes in lifestyle with increased in physical activities, regular exercise and a diet with a low proportion of carbohydrates y rich in poliunsatured fatty acid, such as omega-3 fatty acid as primary intervention. If needed, this strategie must be supplemented with pharmacological therapies such as monotherapy with statins or a combination of fibrates plus omega-3.fatty acid. Lipid abnormalities that define AD have a high prevalence in LA; the interaction between non-healthy lifestyle, inheritance and epigenetic changes, possibly are its cause. AD is an important cause of cardiovascular residual risk (CVRR), that must be diagnosed and treated. It is important and neccesary to design a global study of risk factors in LA to know the true prevalence of AD.

Analysis of the Cochrane Review: Fibrates for secondary prevention of cardiovascular disease and stroke. / Análise da Revisão Cochrane: fibratos na prevenção secundária de doença cardiovascular e acidente vascular cerebral.

The influence of fibrates on cardiovascular risk has been the focus of several clinical trials. This Cochrane Collaboration Systematic Review evaluated the efficacy of fibrates for secondary prevention of cardiovascular events and stroke, analyzing 13 randomized controlled trials, in a total of 16 112 participants with a history of cardiovascular disease. Fibrates showed a protective effect for the composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI) and vascular death, mainly due to reduction in the risk of non-fatal or fatal MI. Nonetheless, these results largely relied on studies including clofibrate, a drug withdrawn from the market in 2002. No statistically significant differences regarding adverse events were found between fibrates and placebo. Although insufficient to support the routine prescription of fibrates in this setting, this evidence should be taken into account when deciding on lipid-modifying therapy in dyslipidemic patients with a history of cardiovascular disease.

Dislipidemia aterogénica en latino américa: prevalencia, causas y tratamiento / Atherogenic dyslipidemia in Latin America: prevalence, causes and treatment

En las guías clínicas actuales, la dislipidemia aterogénica (DA) es una entidad no muy atendida. Debido a las frecuentes alteraciones en los lípidos asociados a la DA en Latino América (LA). Métodos: organizamos un grupo de expertos denominado Academia Latino Americana para el estudio de los Lípidos (ALALIP) para así generar un documento con análisis de su prevalencia y recomendaciones terapéuticas prácticas. Se utilizó la metodología Delphi modificada, con una revisión integral de la literatura y énfasis en las publicaciones con implicaciones para LA. Subsecuentemente, desarrollamos preguntas claves para ser discutidas. Resultados: En Latinoamérica (LA) no existe un estudio global sobre los factores de riesgo que representan a la totalidad de la población. El análisis sistemático de las encuestas nacionales de salud y de los estudios sistemáticos de cohorte muestran consistentemente una alta prevalencia de las anormalidades lipídicas que definen la DA. La concentración baja del colesterol unido a las lipoproteínas de alta densidad (C-HDL) varía entre 34,1% a 53,3% y la de triglicéridos (TG) elevados del 25,5% al 31,2%, con mayor prevalencia entre los hombres. La DA bien puede ser tratada con los cambios del estilo de vida (CTEV) como ncremento en laactividad física, dieta baja en carbohidratos y alta en ácidos grasos poliinsaturados, tales como los ácidos grasos omega-3 como intervención primaria. De ser necesario, esta estrategia sera suplementada con terapia farmacológica como la monoterapia con estatinas o la combinación de fibratos/ácidos grasos omega-3. Conclusiones: Las anormalidades lipídicas que definen la DA tienen una elevada prevalencia en LA; su interacción con un estilo de vida no saludable, herencia y cambios epigenéticos están ligados a sus posibles causas. La DA es una causa importante de riesgo cardiovascular residual (RCVR) que debe ser diagnosticada y tratada. Es importante y necesario diseñar un estudio global de factores de riesgo en LA para conocer la real prevalencia de la DA(AU)

In the current clinical guidelines, atherogenic Med Interna (Caracas) 2017; 33 (3): 121 - 139 Dislipidemia Aterogénica en Latino América: Prevalencia, causas y tratamiento Carlos I. Ponte-N, Jesús E. Isea-Pérez, Alberto J. Lorenzatti, Patricio López-Jaramillo, Fernando Stuardo Wyss-Q, Xavier Pintó, Fernando Lanas, Josefina Medina, Livia T. Machado-H, Mónica Acevedo, Paola Varleta Alfonso Bryce, Carlos Carrera, Carlos Ernesto Peñaherrera, José Ramón Gómez-M, Alfredo Lozada, Alonso Merchan-V, Daniel Piskorz, Enrique Morales, María Paniagua, Félix Medina-Palomino, Raúl Alejandro Villar-M, Leonardo Cobos, Enrique Gómez-Álvares, Rodrigo Alonso, Juan Colan, Julio Chirinos, Jofre Lara, Vladimir Ullauri, Ildefonso Arocha Documento de la posición de expertos de la Academia Latino Americana para el estudio de los Lípidos (ALALIP) y avalado por la Sociedad Interamericana de Cardiología (SIAC), Sociedad Sur Americana de Cardiología (SSC), el Colegio Panamericano de Endotelio (CPAE) y la Sociedad Internacional de Aterosclerosis (IAS). Publicado en conjunto con las Revistas de la Sociedad Venezolana de Medicina Interna y de la Sociedad Venezolana de ndocrinología y Metabolismo. dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named Latin American Academy for the study of Lipids (ALALIP), to generate a document to analize it´s prevalence and to offer practical recommendations. Methodology: Using the Delphi methodology, we conducted a comprehensive literature review, with emphasis on those publications with implications for LA. Subsequently we developed key questions to be discussed. Results: In LA There is no a global study on risk factors that represent the entire population. The systematic analysis of national health surveys and regional cohort studies showed a consistent high prevalence of the lipid abnormalities that define AD. Low high density lipoprotein cholesterol (HDL-C) ranges from 34.1% to 53.3% and elevated triglycerides (TG) from 25.5% to 31.2% more prevalent in men. There are multiple causes: high consumption of foods with a high caloric density, cholesterol and trans fats, sedentary lifestyle and epigenetic changes. AD must be well treated with therapeutic changes in lifestyle with increase in physical activities, regular exercise and a diet with a low proportion of carbohydrates and rich in poliunsatured fatty acid, such as omega-3 fatty acids as primary intervention. If needed, this strategy must be supplemented with pharmacological therapies such as monotherapy with statins or a combination of fibrates plus omega-3. fatty acid. conclusions: Lipid abnormalities that define AD have a high prevalence in LA; the interaction between non-healthy lifestyle, inheritance and epigenetic changes, possibly are the cause. AD is an important cause of cardiovascular residual risk (CVRR), that must be diagnosed and treated It is important and necesary to design a global study of risk factors in LA to know the true prevalence of AD(AU)

[Lipid-lowering drugs and PCSK9]. / Fármacos hipolipemiantes y PCSK9.

PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9. This article aims to review the effects of different lipid-lowering drugs on plasma PCSK9 concentrations. Overall, statins increase blood PCSK9 levels, an effect that is enhanced by ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease PCSK9 levels.

[Fibrates therapy: Rational use fenofibrate 2016. Executive summary]. / Terapia con fibratos: uso racional del fenofibrato 2016. Resumen ejecutivo.

To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to control and monitoring of treatment is also done, as well as benefits of fenofibrate not linked directly to their lipid-lowering effect.

[Therapeutic targets in the treatment of dyslipidemia: HDL and non-HDL cholesterol]. / Dianas terapéuticas en el tratamiento de las dislipemias: colesterol no unido a lipoproteínas de alta densidad y colesterol unido a lipoproteínas de alta densidad.

Atherogenic dyslipidemia (AD) consists of the combination of an increase in very low density lipoproteins (VLDL), which results in increased plasma triglyceride (TG) levels, with a reduction of levels of high-density lipoprotein bound cholesterol (HDL-C), also accompanied by a high proportion of small and dense LDL particles. AD is considered the main cause of the residual risk of experiencing cardiovascular disease (CVD), which is still presented by any patient on treatment with statins despite maintaining low-density lipoprotein bound cholesterol (LDL-C) levels below the values considered to be the objective. Non-HDL cholesterol (non-HDL-c) reflects the number of atherogenic particles present in the plasma. This includes VLDL, intermediate density lipoproteins (IDL) and LDL. Non-HDL-c provides a better estimate of cardiovascular risk than LDL-c, especially in the presence of hypertriglyceridemia or AD. The European guidelines for managing dyslipidemia recommend that non-HDL-c values be less than 100 and 130 mg/dL for individuals with very high and high cardiovascular risk, respectively. However, these guidelines state that there is insufficient evidence to suggest that raising HDL-c levels incontrovertibly results in a reduction in CVD. Therefore, the guidelines do not set recommended HDL-c levels as a therapeutic objective. The guidelines, however, state that individuals with AD on treatment with statins could benefit from an additional reduction in their risk by using fibrates.

[The combinations of statins and fibrates: pharmacokinetic and clinical implications]. / Combinaciones de estatinas y fibratos: implicaciones farmacocinéticas y clínicas.

With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate.

[Indications for the combination of pravastatin and fenofibrate according to the cardiovascular risk level. Common clinical situations]. / Indicaciones de la combinación de pravastatina y fenofibrato según el nivel de riesgo cardiovascular. Situaciones clínicas habituales.

In diabetes, metabolic syndrome, some types of familial dyslipidemia, ischemic pathology of atheromatous origin and renal failure, the presence of mixed dyslipidemia is common. In other words, there is an excess of cholesterol and triglycerides, associated or not with HDL-c deficiency. These clinical conditions are associated with high to very high cardiovascular risk. It is appropriate when treating these conditions to achieve an overall control of lipid metabolism abnormalities, in terms of excess cholesterol carried by atherogenic lipoproteins (LDL-c and non-HDL-c) and triglyceride excess and deficit of HDL-c. To achieve this overall control is necessary to correct the potential causes of secondary dyslipidemia, improve lifestyle habits and use a drug from the statin family, and it is often necessary to combine a drug from the fibrate family. This combination has been shown to be effective and safe in the overall control of dyslipidemia and the cardiovascular risk prevention in patients at high risk. This combination has been shown to have a favorable eff ect in the population with diabetes and microangiopathy, both in the retina and in the glomerulus. For patients with moderate renal failure, the use of fibrates is controversial, and there are marked disagreements between the recommendations issued by various organizations and expert consensus groups.

Agonistas PPAR (Rosiglitazona, Bezafibrato e Fenofibrato) e alterações bioquímicas e estruturais em órgãos-alvo de camundongos C57BL/6 alimentados com dieta hiperlipídica rica em sacarose / PPAR agonists (Rosiglitazone, Bezafibrate and Fenofibrate) and biochemical and structural alterations in organs target of C57BL/6 mice fed high-fat high sucrose chow

Este trabalho teve o objetivo de estudar o efeito de medicamentos com diferentes ações agonista PPAR (rosiglitazona, fenofibrato e bezafibrato) sobre o perfil lipídico, glicídico e alterações na massa corporal e morfologia do tecido adiposo e pancreático em modelo de diabetes e sobrepeso induzido por dieta. Camundongos C57BL/6 (2 meses de idade) foram alimentados com dieta padrão (SC, n=10) ou dieta hiperlipídica rica em sacarose (HFHS, n=40) por 6 semanas. Logo após, os animais HFHS foram subdividos em: HFHS não tratado e HFHS tratado com rosiglitazona (HFHS-Ro), fenofibrato (HFHS-Fe) ou bezafibrato (HFHS-BZ) (5 semanas). Os camundongos alimentados com dieta HFHS apresentaram maior glicemia e insulina de jejum (+33% e +138%, respectivamente), intolerância à glicose, resistência à insulina, aumento da massa corporal (MC) (+20%) e adiposidade, hipertrofia de adipócitos e redução da imunocoloração para adiponectina no tecido adiposo. No pâncreas houve aumento da massa (+28%), acúmulo de gordura (+700%), hipertrofia da ilhota (+38%) e redução da imunocoloração para GLUT-2 (-60%). A rosiglitazona diminuiu a glicemia e insulina de jejum, porém induziu o ganho de MC e hipertrofia cardíaca. O fenofibrato estabilizou a MC, enquanto o bezafibrato levou a perda de MC. Apenas o bezafibrato impediu a hipertrofia da ilhota. A imunocoloração para GLUT-2 foi aumentada por todos os medicamentos, e não houve alterações na imunocoloração para o PPARalfa. Sinais morfológicos de pancreatite foram vistos no grupo HFHS-Fe, apesar dos níveis normais de amilase e lipase séricos. A rosiglitazona exacerbou a infiltração intrapancreática de gordura (+75% vs. HFHS), e o bezafibrato aumentou a imunocoloração para o PPARbeta/delta nas ilhotas pancreáticas. Em conclusão, o bezafibrato apresentou um efeito mais amplo sobre as alterações metabólicas, morfológicas e biométricas decorrentes da dieta HFHS, sugerindo que a inibição das três isoformas do PPAR seria melhor do que a inibição...

This work aimed to evaluate the effect of peroxisome proliferator-activated receptor (PPAR) agonists (rosiglitazone, fenofibrate and bezafibrate) on lipid and glucose metabolism, body mass, and adipose and pancreatic tissue morphology in a model of diet-induced type 2 diabetes and overweight in mice. Two-month-old male C57BL/6 mice were fed a standard chow (SC, n=10) or a high-fat high-sucrose chow (HFHS, n=40) for 6 weeks, and then HFHS-fed mice were subdivided by treatment: untreated HFHS and HFHS treated with rosiglitazone (HFHS-Ro), fenofibrate (HFHS-Fe), or bezafibrate (HFHS-Bz) (5 weeks on medication). HFHS-fed mice have altered fasting glucose (+33%) and insulin (+138%), GI, IR, increased body mass (+20%) and fat pad weight, adipocyte hypertrophy, and decreased adiponectin immunostain. They also presented increased pancreatic (+28%) mass, intrapancreatic fat (+700%), islet hypertrophy (+38%), and decreased GLUT-2 immunostain (-60%). Rosiglitazone reduced fasting glucose and insulin but induced weight gain and heart hypertrophy. Fenofibrate impaired body mass gain, while bezafibrate induced weight loss. Only bezafibrate impaired islet hypertrophy. GLUT-2 immunostain was improved by all treatments, and there were no alterations in PPAR-alfa stain. There were morphological signs of pancreatitis in fenofibrate-treated mice, although there was no alteration in serum amylase and lipase. Rosiglitazone exacerbated pancreatic fat infiltration (+75% vs. HFHS group), and bezafibrate increased PPAR-beta expression in pancreatic islets. In conclusion, bezafibrate showed a wider range of action on metabolic, morphologic, and biometric alterations due to HFHS intake, suggesting that inhibiting the three PPAR isoforms is better than inhititing each isoform alone. Rosiglitazone exacerbated body mass gain, pancreatic fat infiltration and induced heart hyperthophy as well, thus, precaution has to be taken in prescribing rosiglitazone to obese patients.

Elevando el colesterol HDL: ¿Cuál es la mejor estrategia?: [revisão] / Raising HDL cholesterol: which is the best strategy?: [review]

Após atingir as metas para os níveis de LDL-colesterol, é imperativo alcançar a meta do HDL-colesterol, por suas conhecidas propriedades antiaterogênicas confirmadas amplamente em muitos estudos epidemiológicos. Esta revisão analisa de maneira objetiva e concisa as diversas alternativas disponíveis na prática clínica diária para aumentar os níveis de HDL-colesterol em nosoos pacientes, com o objetivo de alcançar melhores prognósticos em termos de morbimortalidade cardiovascular.

After having reached the objective for the LDL cholesterol levels, it becomes imperative to reach the objective for HDL cholesterol, known for its anti-atherogenic properties, generally confirmed in many epidemiological studies. This review deals, in a clear and concise manner, with the different alternatives available in daily clinical practice to raise the HDL cholesterol levels of patients, to achieve better outcomes in terms of morbidity and mortality in cardiovascular disease.

Lipoproteínas de alta densidad (HDL). ¿Un objetivo terapéutico en la prevención de la aterosclerosis? / High densiy lipooproteins (hdl). a therapeutic objective i the atheroscleerosis prevention?

Las lipoproteínas de alta densidad (HDL) son una familia de partículas que difieren en tamaño, densidad y composición química. La heterogeneidad de las HDL resulta de la velocidad de síntesis y de catabolismo de las partículas, y de la acción de enzimas y proteínas de transporte que las remodelan continuamente. Los bajos niveles de colesterol HDL correlacionan con un riesgo elevado de desarrollar enfermedad aterosclerosa coronaria. La disminución de las HDL afecta el transporte reverso de colesterol, que es la vía metabólica responsable de la remoción del colesterol excedente de la células periféricas y su transporte hacia el hígado para reciclarlo o eliminarlo. Las HDL poseen además propiedades antiinflamatorias, antioxidativas, antiagregatorias, anticoagulantes y profibrinolíticas in vitro . Algunas de estas propiedades potencialmente antiaterosclerosas, también se han puesto de manifiesto in vivo con infusiones de HDL. Estas evidencias, además de la protección que se logra en modelos animales genéticamente modificados, permite plantear a las HDL como un objetivo primario en la prevención de la aterosclerosis coronaria. Algunos estudios epidemiológicos han demostrado una reducción importante en el riesgo cardiovascular asociado a elevaciones del colesterol HDL, principalmente en prevención secundaria. En consecuencia, elevar las concentraciones de las HDL a través de medidas higiénicas como el ejercicio aeróbico, la pérdida de peso y eliminar el tabaquismo, es ampliamente recomendado para reducir el riesgo coronario. Cuando las medidas higiénicas fallan, la intervención farmacológica con niacina o fibratos debe ser considerada en ciertos pacientes con niveles bajos de HDL. Por último, las diferentes subclases de HDL no poseen las mismas propiedades antiaterogénicas, lo que sugiere que las intervenciones tanto higiénicas como farmacológicas se deberán enfocar en el futuro hacia incrementos de la funcionalidad de las HDL, más que a incremento en la concentración del colesterol HDL.

High density lipoproteins (HDL) are a family of heterogeneous particles that vary in size, density and chemical composition, as a result of their synthesis and catabolism rates, and a continuous intravascular remodeling by the action of enzymes and transport proteins. Low plasma levels of HDL correlate with a high risk of atherosclerotic heart disease. Such a diminished concentration of HDL affect reverse cholesterol transport, which is the metabolic pathway responsible for the movement of cholesterol excess from peripheral tissues to the liver for recycling or excretion. In addition, HDL possess anti-inflammatory, anti-oxidative, anti-aggregatory, anti-coagulant, and pro-fibrinolytic properties, as has been demonstrated by in vitro studies. Some of those potentially anti-atherosclerotic in vitro-properties has been corroborated by HDL infusion in vivo. Such evidences and the protection of susceptible animals from atherosclerosis by transgenic manipulation of HDL metabolism, raise the possibility to focus the HDL plasma levels as a main target in coronary hearth disease prevention. Intervention trials have shown an important reduction in coronary events by rising HDL-cholesterol, mainly in the secondary prevention. Increasing HDL plasma levels by hygienic intervention such as aerobic exercise, weight loss and stop smoking is strongly recommended to reduce coronary risk in primary prevention. Pharmacological intervention to rise the HDL plasma levels with niacin or fibrates, should be considered in some patients as an alternative when hygienic intervention fails. Finally, it most be taken into account that the different HDL subclasses does not possess the same anti-atherosclerotic properties, suggesting that hygienic and pharmacological interventions should focus to increase HDL functionality rather than HDL-cholesterol plasma levels. (Arch Cardiol Mex 2004; 74:53-67).