Lipid profile and statin use in critical care setting: implications for kidney outcome / Perfil lipídico e uso de estatina em terapia intensiva: implicações no desfecho renal

ABSTRACT Objective: To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay. Methods: Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study. Results: Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease. Conclusion: Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.

RESUMO Objetivo: Determinar se o uso pré-admissão hospitalar de estatina está associado com menor necessidade de diálise e/ou óbito durante internação em unidade de terapia intensiva. Métodos: Análise de coorte prospectiva. Foram incluídos consecutivamente 670 pacientes admitidos na unidade de terapia intensiva de um hospital acadêmico de cuidados terciários. Os pacientes incluídos deveriam ter entre 18 e 80 anos e ter sido admitidos na unidade de terapia intensiva nas últimas 48 horas. Resultados: A média da idade dos pacientes foi de 66±16,1 anos. O índice de massa corporal foi de 26,6±4/9kg/m2 e a circunferência abdominal média foi de 97±22cm. O grupo que fez uso de estatina pré-admissão hospitalar (18,2% dos pacientes) necessitou menos de terapia de substituição renal e/ou evoluiu para óbito (OR: 0,41; IC95%: 0,18-0,93; p=0,03). O grupo que fez uso de estatina também apresentou menor risco de evoluir com sepse durante a internação na unidade de terapia intensiva (OR: 0,42; IC95%: 0,22-0,77; p=0,006) e teve menor duração da hospitalização (14,7±17,5 dias versus 22,3±48 dias; p=0,006). A terapia pré-admissão hospitalar com estatina foi associada a papel protetor no cenário da terapia intensiva independentemente de variáveis confundidoras, como sexo, idade, proteína C-reativa, necessidade de ventilação mecânica, uso de vasopressores e diagnóstico de diabetes e/ou coronariopatia. Conclusão: A terapia com estatina antes da admissão hospitalar foi associada a menor mortalidade, menor necessidade de terapia de substituição renal e taxa de ocorrência de sepse.

Efecto del ciprofibrato sobre el metabolismo del colesterol HDL y la capacidad antioxidante plasmática en el ratón / Effect of ciprofibrate on HDL cholesterol metabolism and plasma anti-oxidant capacity in mice

Antecedentes: Las dislipidemias, ya sea un aumento en los niveles de colesterol LDL y/o una disminución en las cifras de colesterol HDL, son muy relevantes para el desarrollo de la enfermedad cardiovascular ateroesclerótica, siendo el colesterol HDL bajo la dislipidemia más frecuente en la población chilena. Con respecto al colesterol HDL bajo y los tri -glicéridos elevados, los fibratos, agonistas del receptor nuclear PPAR-a que modula la transcripción de genes involucrados en el metabolismo de lípidos, representan una importante alternativa de manejo farmacológico de las dislipidemias. Sin embargo, estudios clínicos recientes no han sido concluyentes con respecto a su beneficio real sobre el control de la ateroesclerosis cuando se usan combinados con estatinas. Objetivo: Evaluar el impacto de la administración de fibratos sobre el metabolismo del colesterol HDL y la función antioxidante del plasma usando el ratón como modelo experimental. Metodología: Los ratones de la cepa C57BL/6 fueron tratados con ciprofibrato al 0,2% en dieta control durante 7 días. Luego del tratamiento, se analizaron los niveles de colesterol plasmático y triglicéridos, la expresión hepática de proteínas claves involucradas en el metabolismo de colesterol HDL, el contenido de colesterol hepático, la secreción de colesterol biliar y el daño oxidativo y la función antioxidante plasmática. Resultados: El tratamiento con ciprofibrato disminuyó significativamente los niveles de triglicéridos plasmáticos y la expresión hepática del receptor de HDL SR-BI, efecto que se correlacionó con un aumento en el tamaño de las partículas de HDL, pero no en los niveles de colesterol HDL. Además, el ciprofibrato disminuyó los niveles proteicos de los transportadores de colesterol ABCG1 y ABCG8, aunque no modificó ABCA1, en conjunto con una reducción del contenido hepático de colesterol y un aumento en la secreción de colesterol hacia la bilis. Finalmente, el uso de este hipolipemiante mejoró la función antioxidante del plasma, aunque se detectó un aumento en el daño nitrosativo de las proteínas plasmáticas. Conclusión: Este estudio ha permitido obtener nueva información sobre el efecto metabólico y funcional de la administración de fibratos en ratones, lo cual podría ayudar comprender los resultados de estudios clínicos recientes que han usado esta clase de hipolipemiantes en humanos.

Background: Increased serum levels of LDL cholesterol and/or decreased values of HDL cholesterol are very relevant for atherosclerotic cardiovascular disease. Low HDL cholesterol is the most prevalent dyslipidemia in the Chilean population. Regarding reduced HDL cholesterol and high triglyceride levels, fibrates, nuclear receptor PPAR-a agonists that modulate transcription of genes involved in lipid metabolism, represent an important alternative for pharmacological management of dyslipidemia. However, recent clinical studies have been inconclusive with respect to their real benefit on atherosclerosis when used in combination with statins. Aim: To evaluate the impact of fibrate administration on HDL cholesterol metabolism and antioxidant plasma functionality using the mouse as experimental model. Methodology: Using wild-type C57BL/6 mice, ciprofibrate was administered at 0.2% in chow diet for 7 days. After treatment, plasma cholesterol and triglycerides levels, hepatic expression of key proteins involved in HDL cholesterol metabolism, liver cholesterol content, biliary cholesterol secretion, and plasma oxidative damage and antioxidant function were analyzed. Results: Ciprofibrate treatment significantly decreased plasma triglycerides levels and hepatic HDL receptor SR-BI expression. This latter finding was associated with increased HDL particle size, without changes in HDL cholesterol levels. Furthermore, ci-profibrate decreased hepatic expression of cholesterol transporters ABCG1 and ABCG8, but not ABCA1, which correlated with reduced liver cholesterol content and increased biliary cholesterol secretion. Fina-lly, fibrate therapy improved plasma antioxidant func-tion, even though increased nitrosative plasma protein damage was detected. Conclusion: This study has provided new information on metabolic and functional effects derived from fibrate use in mice and it may help to better understand recent clinical findings using this lipid-lowering drug class in humans.

El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia / Nicotinic acid increases cellular transport of high density lipoprotein cholesterol in patients with hypoalphalipoproteinemia

Background: Plasma high density lipoproteins (HDL) are involved in reverse cholesterol transport mediated by the scavenger receptor class B type I (SR-BI). Nicotinic acid increases HDL cholesterol levels, even though its specific impact on SR-BI dependent-cellular cholesterol transport remains unknown. Aim: To determine the effect of nicotinic acid on HDL particle functionality in cholesterol efflux and uptake mediated by SR-BI in cultured cells in hypoalphalipoproteinemic patients. Material and Methods: In a pilot study, eight patients with low HDL (≤ 40 mg/dL) were treated with extended release nicotinic acid. HDL cholesterol and phospholipid levels, HDL2 and HDL3 fractions and HDL particle sizes were measured at baseline and post-therapy. Before and after nicotinic acid treatment, HDL particles were used for cholesterol transport studies in cells transfected with SR-BI. Results: Nicotinic acid treatment raised total HDL cholesterol and phospholipids, HDL2 levels as well as HDL particle size. Nicotinic acid significantly increased HDL cholesterol efflux and uptake capacity mediated by SR-BI in cultured cells. Conclusions: Nicotinic acid therapy increases SR-BI-dependent HDL cholesterol transport in cultured cells, establishing a new cellular mechanism by which this lipid-lowering drug appears to modulate HDL metabolism in patients with hypoalphalipoproteinemia.

An Open label, Prospective, Multi-Center, Observational Study to Evaluate the Lipid Lowering Efficacy and Safety of Rosuvastatin in Indian Dyslipidemics in Routine Clinical Practice.

Altered cholesterol levels in the blood or dyslipidemia is a major modifiable risk factor for CVD and is closely associated with the pathophysiology of CVD. Asians, particularly Indians, have a unique pattern of dyslipidemia; with lower HDL cholesterol, increased triglyceride levels and higher proportion of small dense LDL cholesterol, with characteristic centripetal obesity. ‘Statins’ belong to the group of 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors that have been shown to reduce levels of total and LDL cholesterol. Study Objective: To evaluate the lipid lowering efficacy and safety of Rosuvastatin in Indian dyslipidemics in routine clinical practice by measuring the percent change in Total Cholesterol, LDL, TG and HDL over a period of 16 weeks. Methodology : This was a multicentric, open-labeled, post-marketing surveillance study. A committee of key opinion leaders was formed. A total of 1200 doctors were approached of whom 800 provided us with subject data. Each participating doctor was given case report forms and requested to recruit patients according to the inclusion and exclusion criteria. Lipid profile of each recruited patient was done before initiating therapy and at the end of 4 months. Rosuvastatin was given at a dose of either 5mg/ 10mg OD for 4 months. Results : A total of 11, 656 subjects were recruited into this study out of which 10, 410 complete case report forms were considered (n=10410). The study included 65% males and 35% females. Majority of the subjects were in the age group of 46-55years (35.2%) and 56-65 years (29.4%). In this study, the total cholesterol (TC), LDL-C, Triglycerides (TG) has significantly decreased by 46.13%, 53.74% and 41.93% respectively. Also the HDLC levels increased by 26.84%, thereby, indicating a significant change in the levels of all the dyslipidemic indicators. With the reported number of adverse events (n=4) related to Rosuvastatin, it is evident that the drug is safe and tolerable. There were no significant changes observed in the liver and renal function tests with Rosuvastatin reiterating their safety. Conclusion : Rosuvastatin has shown greater efficacy in lowering LDL cholesterol and non-HDL-cholesterol concentrations. It has been shown to enable more patients to reach their LDL cholesterol goals and to do so with an acceptable safety profile.

Hydrochloride pioglitazone protects diabetic rats against podocyte injury through preserving glomerular podocalyxin expression / O cloridrato de pioglitazona protege ratos diabéticos contra a injúria aos podócitos por meio da preservação da expressão de podocalixina glomerular

Objective: We sought to test the effect of different dosages of pioglitazone (PIO) on the glomerular expression of podocalyxin and urinary sediment podocalyxin excretion and to explore the potential renoprotective mechanism. Materials and methods: Type 1 diabetes induced with streptozotocin (65 mg/kg) in 36 male Sprague-Dawley rats were randomly allocated to be treated with vehicle or 10, 20, 30 mg/kg/d PIO respectively for 8 weeks. Eight rats were enrolled in the normal control group. Results: At 8th week, rats were sacrificed for the observation of kidney injury through electron microscope. Glomerular podocalyxin production including mRNA and protein were determined by RT-PCR and immunohistochemistry respectively. Levels of urinary albumin excretion and urinary sediment podocalyxin, kidney injury index were all significantly increased, whereas expression of glomerular podocalyxin protein and mRNA were decreased significantly in diabetic rats compared to normal control. Dosages-dependent analysis revealed that protective effect of PIO ameliorated the physiopathological changes and reached a peak at dosage of 20 mg/kg/d. Conclusion: PIO could alleviate diabetic kidney injury in a dose-dependent pattern and the role may be associated with restraining urinary sediment podocalyxin excretion and preserving the glomerular podocalyxin expression. .

Objetivo: Buscamos testar os efeitos de diferentes doses de pioglitazona (PIO) sobre a expressão glomerular de podocalixina e sobre a excreção de podocalixina em células do sedimento urinário, além de explorar o potencial mecanismo de proteção renal. Materiais e métodos: O diabetes tipo 1 foi induzido em 36 ratos Sprague-Dawley machos com estreptozotocina (65 mg/kg). Os animais foram tratados apenas com o veículo, ou com 10, 20, 30 mg/kg/d de PIO por 8 semanas. Oito ratos foram colocados no grupo controle. Resultados: Na oitava semana, os ratos foram sacrificados para se observar a lesão renal em microscopia eletrônica. A produção de podocalixina glomerular, incluindo mRNA e proteína, foi determinada por RT-PCR e imuno-histoquímica, respectivamente. Os níveis urinários de albumina e podocalixina nas células do sedimento urinário e o índice de lesão renal estavam todos significativamente aumentados, enquanto a expressão glomerular da proteína podocalixina e do mRNA estava significativamente diminuída em ratos diabéticos comparados com o controle normal. A análise dos efeitos dose-dependentes revelou que o efeito protetor da PIO melhorou as mudanças fisiopatológicas e atingiu um pico na dose de 20 mg/kg/dia. Conclusão: A PIO pode melhorar a injúria renal de forma dose-dependente e este papel pode estar associado com a prevenção da excreção de podocalixina nas células do sedimento urinário e com a preservação da expressão glomerular de podocalixina. .

Effect of moderate ethanol administration on biochemical indices in streptozotocin-diabetic Wistar rats / Efecto de la administración moderada de etanol sobre los índices bioqumicos en ratas Wistar diabéticas por estreptozotocina

OBJECTIVE: This study was designed to evaluate the effect of moderate ethanol administration on the biochemical indices in streptozotocin (STZ)-diabetic rats. METHODS: Twenty-four male Wistar rats were divided into four groups of six animals each. Groups one and two contained non-diabetic normal rats and normal rats treated with ethanol, respectively. Group three was untreated STZ-diabetic rats and group four was made up of ethanol-treated STZ-diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (35 mg/kg), while ethanol (10%v/v) was given at a dose 2 g/kg thrice per week for three weeks. After the last dose of ethanol and an overnight fasting, rats were sacrificed by cervical dislocation. Blood was collected by syringe from the heart into plain centrifuge tubes. RESULTS: Moderate ethanol administration to STZ-diabetic rats caused a significant (p < 0. 05) increase in relative weight of liver relative to normal. Ethanol intake in STZ-diabetic rats produced an insignificant (p > 0. 05) effect on the levels of fasting blood glucose (FBG) and HbA1c rrelative to the untreated-diabetic group. Moderately, ethanol administration to STZ-diabetic rats produced a marked and significant (p < 0. 05) increase in the levels of serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol and the activities of alanine aminotransferase relative to untreated diabetic rats. Ethanol-treated diabetic rats had significantly (p < 0. 05) lower high-density lipoprotein (HDL)-cholesterol levels, while the activities of lactate dehydrogenase and α-amylase were insignificantly (p > 0. 05) affected. There were no significant (p > 0. 05) differences in all the biochemical indices in normal rats relative to ethanol-treated normal rats. CONCLUSIONS: Moderate ethanol administration did not affect FBG and HbA1c , but altered the lipid profile of STZ-diabetic rats. Moderate ethanol intake may further increase the risk of complications in diabetes.

OBJETIVO: Este estudio se diseñó con el propósito de evaluar el efecto del uso de etanol moderado sobre los índices bioquímicos en ratas Wistar diabéticas por estreptozotocina (STZ). MÉTODOS: Veinticuatro ratas Wistar machos fueron divididas en cuatro grupos de seis animales cada uno. Dos de los grupos tenían ratas normales no diabéticas y ratas normales tratadas con etanol, respectivamente. El tercer grupo estaba formado por ratas diabéticas por STZ no tratadas, y el cuarto por ratas diabéticas por STZ tratadas con etanol. La diabetes fue inducida mediante una inyección intraperitoneal de STZ (35 mg/kg), mientras que el etanol (10% v/v) fue administrado en dosis de 2 g/kg tres veces por semana durante tres semanas. Tras la última dosis de etanol y un ayuno de una noche, las ratas fueron sacrificadas mediante dislocación cervical. La sangre fue recogida del corazón con jeringuillas e introducida en tubos para centrífuga sin graduación. RESULTADOS: La administración moderada de etanol a ratas diabéticas por STZ, causó un aumento significativo (p < 0.05) en el peso relativo del hígado con relación al normal. La ingestión de etanol en ratas diabéticas por STZ tuvo un efecto insignificante (p > 0.05) en los niveles de glucosa en sangre en ayuno (GSA) y HbA1c en relación con grupos diabéticos no tratados. En medida moderada, la administración de etanol a ratas diabéticas por STZ produjo un aumento marcado y significativo (p < 0.05) en los niveles de colesterol total en suero, triglicéridos, el colesterol asociado con las lipoproteínas de baja densidad, o colesterol LDL, y la actividad de la aminotransferasa alanina en relación con las ratas diabéticas no tratadas. Las ratas diabéticas tratadas con etanol tuvieron niveles significativamente disminuidos de colesterol asociado con las lipoproteínas de alta densidad, o colesterol HDL, en tanto que la actividad del lactato deshidrogenasa y la α-amilasa no fue afectada significativamente (p > 0.05). No hubo diferencias significativas (p > 0.05) en todos los índices bioquímicos en las ratas normales con respecto a las ratas normales tratadas con etanol. CONCLUSIONES: El suministro moderado de etanol no afectó el GSA ni el HbA1c , pero alteró el perfil lípido de las ratas diabéticas por STZ. La ingestión moderada de etanol puede aumentar a un más el riesgo de las complicaciones de la diabetes.

Evaluation of antihyperlipidemic activity of ethanolic extract of Cassia auriculata flowers.

Hyperlipidemia is a major risk factor for development of coronary artery disease. Cassia auriculata is traditionally used in India for medicinal purposes. In this study, effect of ethanolic extract of Cassia auriculata flowers (Et-CAF) was investigated in Triton WR1339-induced hyperlipidemic rats. Treatment with the Et-CAF (450 mg/kg b.wt) significantly reduced the total cholesterol (TC), triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels and significantly increased the high-density lipoprotein (HDL) level associated with reduction of atherogenic index in hyperlipidemic rats. However, there was no change in the serum lipid profile of normal rats treated with Et-CAF alone. The results suggest that Et-CAF has a beneficial effect in treating hyperlipidemia and may serve as a potential drug for prevention of hyperlipidemic atherosclerosis.

HDL: o yin-yang da doença cardiovascular / HDL: the yin-yang of cardiovascular disease

Estudos epidemiológicos mostram relação inversa entre níveis plasmáticos de HDL-colesterol (HDL-C) e incidência de doença cardiovascular (DCV). O papel antiaterogênico da HDL é atribuído às suas atividades anti-inflamatória, antitrombótica e antioxidante, além de sua participação no transporte reverso de colesterol (TRC), processo pelo qual a HDL remove colesterol dos tecidos periféricos, incluindo macrófagos da íntima arterial, e o transporta para o fígado para ser excretado pela bile. Com base nesses fatos, o HDL-C tornou-se alvo atrativo para a prevenção da DCV. No entanto, o fracasso do torcetrapib, droga que aumenta substancialmente os níveis de HDL-C, em prevenir DCV, além do conhecimento gerado por estudos de modelos animais e doenças monogênicas que afetam a concentração de HDL-C, tem suscitado questionamentos sobre o papel antiaterogênico da HDL. Esta revisão tem como objetivo abordar aspectos atuais do conhecimento da HDL, baseando-se nessas recentes controvérsias.

Epidemiological studies demonstrate an inverse correlation between plasma HDL-cholesterol (HDL-C) concentration and incidence of cardiovascular disease (CVD). The antiatherogenic role of HDL has been attributed to its anti-inflammatory, antithrombotic and antioxidant properties, besides its participation in the reverse cholesterol transport (RCT), whereby cholesterol from peripheral tissues (including macrophages of the arterial intima) is delivered to the liver for excretion in bile. Due to these actions, HDL-C has evolved as an attractive target for prevention of CVD. However, the failure of torcetrapib, drug that substantially increases HDL-C levels, in preventing CVD and data from studies with animal models and with carriers of monogenic disorders affecting HDL-C levels in humans provide conflicting data about HDL being antiatherogenic. This review addresses the current state of knowledge regarding HDL based on these recent controversies.

Severe HDL-c reduction during rosiglitazone therapy in an obese woman with type 2 diabetes / Redução severa de HDL-colesterol durante terapia com rosiglitazona em uma mulher obesa com diabetes tipo 2

Treatment with rosiglitazone has been associated with severe paradoxical HDL-c reductions. To our knowledge, there are very few reports of this reaction occurring when patients are treated without the combination of a fibrate. A case of severe HDL-c lowering in a patient treated with rosiglitazone without a fibrate is presented. The patient has been treated at a private practice clinic in southern Brazil. A 64-year-old woman with a 2-year history of type 2 diabetes mellitus was referred to her endocrinologist in June 2008. Rosiglitazone 4 mg q.d. was prescribed. Nine months later, the patient experienced a 90.90 percent decrease of her HDL-c levels. Rosiglitazone was withdrawn and the HDL-c returned to baseline. This paradoxical HDL-c reduction is a potentially severe adverse event. Patients prescribed rosiglitazone should have their HDL-c levels measured before and during therapy.

O tratamento com rosiglitazona tem sido associado a reduções paradoxais e severas no HDL-c. Há muito poucos relatos dessa reação ocorrendo em pacientes tratados com rosiglitazona sem a combinação com um fibrato. Apresentou-se um caso de diminuição severa no HDL-c em uma paciente tratada com rosiglitazona sem fibrato associado. A paciente foi tratada em uma clínica privada no Sul do Brasil. Uma mulher de 64 anos com história de diabetes melito tipo 2 há 2 anos foi encaminhada ao seu endocrinologista em junho de 2008. Prescreveu-se rosiglitazona 4 mg uma vez ao dia. Nove meses depois, a paciente teve redução de 90,90 por cento em seus níveis de HDL-c. A rosiglitazona foi retirada e o HDL-c retornou aos níveis prévios. Essa redução paradoxal do HDL-c é um evento adverso potencialmente severo. Pacientes aos quais se prescreve rosiglitazona devem ter seus níveis de HDL-c medidos antes e durante o tratamento.

Psyllium husk to increase HDL- Cholesterol; placebo controlled study

To examine the effects of Psyllium husk on HDL-Cholesterol. Single blind placebo controlled study. Study was conducted at department of pharmacology and therapeutics at Basic Medical Sciences Institute [BMSI], Jinnah Postgraduate Medical Centre [JPMC], Karachi, from January 2006 to July 2006. Forty hyperlipidemic patients were included, among which 20 patients were on placebo as control group, and 20 were on Psyllium husk, 3 gram daily, in divided doses for the period of three months. Patients with peptic ulcer, renal disease, hepatic disease, hypothyroidism, diabetes mellitus, and alcoholism were excluded from the study. HDL- Cholesterol was determined by using kit Cat. #303210040 by Eli Tech Diagnostic, France. Data were expressed as the mean +/- SD and [t] test was applied to determine statistical significance as the difference. A probability value of <0.05 was the limit of significance. Two patients were dropped from the study due to low compliance of metallic taste of psyllium husk. Psyllium husk has increased HDL-Cholesterol, in 90 days of treatment, from 34.61 +/- 1.85 to 36.77 +/- 1.96 [mg/dl], which was highly significant statistically when paired [t] test was applied for results. Percentage change was +6.24. It is concluded from this study that Psyllium husk decreases the risk of CHD by increasing HDL-Cholesterol

Modulatory effects of rutin on biochemical and hematological parameters in hypercholesterolemic Golden Syrian hamsters

Flavonoids have been reported to exhibit several pharmacological properties, mainly in cardiovascular and inflammatory diseases. In the present study, we observed that rutin, a known glycosylated flavonoid isolated from Dimorphandra mollis, had a lowering effect on plasma triglyceride levels of diet-induced hypercholesterolemic Golden Syrian hamsters, but did not change total cholesterol and high-density lipoprotein cholesterol levels. Moreover, high-fat or rutin supplemented diets showed no immunotoxic effects, since no significant changes were observed on total white blood cells, granulocytes and mononuclear cells, as well as on the neutrophil apoptosis degree, when compared to untreated animals. Therefore, rutin seems to be a selective and non-toxic modulator of hypercholesterolemia, which can be promising for the development of new drugs.

Os flavonóides possuem diversas propriedades farmacológicas, principalmente nas doenças cardiovasculares e inflamatórias. No presente estudo, observamos que a rutina, um conhecido flavonóide glicosilado isolado da Dimorphandra mollis, diminuiu o nível de triglicerídeos plasmáticos em hamsters Golden Syrian hipercolesterolêmicos sem alterar os níveis de colesterol total e colesterol HDL. Além disso, observamos que dietas hipercolesterolêmicas ou suplementadas com rutina não apresentaram efeito imunotóxico, uma vez que nenhuma alteração significativa foi observada nos leucócitos totais, granulócitos e células mononucleares, bem como no grau de neutrófilos em apoptose, quando comparado com animais não tratados. Portanto, a rutina parece ser um modulador seletivo e não tóxico da hipercolesterolemia, o que pode ser promissor para o desenvolvimento de novos fármacos.

Short-term red wine consumption promotes differential effects on plasma levels of high-density lipoprotein cholesterol, sympathetic activity, and endothelial function in hypercholesterolemic, hypertensive, and healthy subjects

OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7 percent (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine.

Atorvastatin improves arterial stiffness in normotensive normolipidaemic persons with type 2 diabetes.

Increased arterial stiffness is an independent predictor of cardiovascular disease and mortality in middle-aged and olderadults. We measured arterial stiffness by pulse wave velocity (PWV)in brachial-ankle segments by automated oscillometry in 71 normotensive and normolipidaemic subjects with type 2 diabetes (40 males and 31 females). 57 patients (whose baPWV was more than 1400 cm/second) were randomised into two groups, group A (n=29) were given 10 mg atorvastatin daily for 6 months and group B (n=28) were given placebo. After 6 months, atorvastatin group had significant improvement in brachial-ankle pulse wave velocity (baPWV) (1712.03 +/- 349.9 cm/second versus 1558.81 +/- 303.26 cm/ second, p< 0.05). Though the placebo group showed some improvement (1692.03 +/- 425.15 cm/second versus 1636.78 +/- 425.1 cm/second) it was not statistically significant. Despite correlation was noted between baPWV and systolic blood pressure (SBP), there was no significant correlation between the mean baPWV and duration of diabetes, body mass index (BMI), waist circumference, waist-hip ratio (WHR), waist to height ratio (WHtR), glycated haemoglobin (HbA1c), LDL, HDL cholesterol and spot urine albumin creatinine ratio (ACR) at the baseline. The decrement of LDL-cholesterol is correlated with the decrement of the baPWV in the atorvastatin group only (p<0.01).

Effect of atorvastatin on LDL & hs-CRP in a selected Thai population.

BACKGROUND: LDL and hs-CRP are risk factors for vascular events and can be modified by Statin. OBJECTIVE: To evaluate the baseline hs-CRP of a certain Thai population who would need Atorvastatin, to evaluate the dose response of Atorvastatin toward LDL and hs-CRP level, and to evaluate the efficacy and safety of different types of Atorvastatin. MATERIAL AND METHOD: Subjects, who needed Statin therapy, were randomized to receive either 20 mg of Berlin(B)-Atorvastatin(R) or Pfizer(P)-Atorvastatin(R). The cross over took place after 8 weeks of therapy and continued for 16 weeks. Baseline blood tests were compared to 8 and 16 weeks. The effect of two brands of 20 mg Atorvastatin toward serum lipid, LFT, muscle enzyme and hs-CRP were compared. RESULTS: One hundred and ten subjects aged between 20-75 years enrolled in the present study. Fifty-four and 56 patients were randomized to group A and B. Baseline total cholesterol, LDL, HDL, and TG were 251, 174, 55, and 160 mg/dl respectively. There was a wide variation of baseline hs-CRP level. One hundred and seven patients completed this 16 weeks study. Atorvastatin 20 mg lowered TC by 32%, LDL 44% and hs-CRP 10% at 16 weeks for the entire study (p < 0.003). The effect of either Atorvastatin the lipid profiles and hs-CRP were different. There was no significant change in LFT or muscle enzyme. CONCLUSION: Atorvastatin 20 mg has a dramatic effect on the lipid but moderate effect on CRP. The two different types of Atorvastatin (group A and B) have similar effect on both safety and efficacy.

Lipid treatment assessment project II in Thailand (LTAP-II Thailand).

OBJECTIVE: Evaluate treatment practices and their outcomes in Thai patients with hyperlipidemia. The factors contributing to success of treatment were also determined. MATERIAL AND METHOD: A multi-center cross-sectional survey with the support of 98 physicians from 48 hospitals was done. Each physician enrolled up to 20 dyslipidemic patients by simple randomization. RESULTS: One thousand nine hundred twenty one cases, 45.1% males with a mean age of 58.6 years (SD = 9.6) were recruited. The patients were divided into three groups: 1,178 patients with coronary heart disease (CHD) and CHD equivalents, 424 patients with high risk, and 319 patients with low risk. The main targets for treatment were LDL-C levels of< 100, < 130 and < 160 mg/dL for each respective group. As a whole, the risk factors listed in order of frequency were age at risk (78%), hypertension (69. 8%), diabetes mellitus (43.6%), smoking (24.6%), and family history of CHD (6.9%). Obesity (body mass index > or = 25 kg/m2) was found in 53.8% of the patients. Twenty eight percent of the patients experienced CHD or other atherosclerotic diseases. Statin was the commonest prescribed drug (64%) followed by fibrate (25%). The overall success rate was 46.5%. Percentage of cases achieving LDL-C targets in the CHD and CHD equivalents, high and low risk group was 34.6%, 56.4%, and 76.8%, respectively. The patients in the low risk group, being under specialist care and receiving statin therapy reached target of treatment at a significantly higher rate. CONCLUSION: The present study showed that statin was the most common drug used in the management of hyperlipidemia. Patients with CHD and CHD equivalents were the group with least achievement of LDL-C target. The factors contributing to achievement of LDL-C target were lower risk patient, specialist care, and statin therapy.

Efficacy and safety of combination of extended release niacin and atorvastatin in patients with low levels of high density lipoprotein cholesterol.

OBJECTIVE: We investigated the safety and efficacy of combination therapy of extended release (ER) niacin and atorvastatin in patients with low HDL-C and compared the results with atorvastatin monotherapy. METHODS: This open label study recruited consecutive men and women who had coronary artery disease with HDL-C levels <35 mg/dL. These patients were already on atorvastatin therapy targeted to lower low density lipoprotein cholesterol (LDL-C), for a minimum period of 6 months. Group 1, n = 104 (mean age 52.7 years) received ER niacin in addition to atorvastatin and group 2 (n = 106) continued on atorvastatin (mean age 52.3 years). ER niacin dose was built up to a maximum of 1.5 g and atorvastatin dose titrated according to LDL levels in both the groups. The lipoprotein levels at baseline were similar (p = NS). RESULTS: At 9 +/- 1.8 months of follow-up, the mean dose of ER niacin was 1.3 g and atorvastatin 13.2 mg in group 1. In comparison, group 2 patients had mean atorvastatin dose of 15.9 mg. Patients in group 1 had significant elevation in HDL-C cholesterol (39.5 +/- 5.5 vs 35.7 +/- 4.5 mg/dL), reduction in total cholesterol (156.4 +/- 31 vs 164.5 +/- 39.3 mg/dL) and also LDL-C (88.9 +/- 28.3 vs 99.8 +/- 35.4 mg/dL) compared to group 2 (all p < 0.05). The magnitude of reduction in triglyceride levels was not significant between the groups (140.1 +/- 40.4 vs 145.2 +/- 46.5 mg/dL) (p = NS). No major adverse events or clinical myopathy occurred in either groups. Four patients (4%) discontinued ER niacin (2 due to gastro-intestinal symptoms and 2 due to worsening of diabetes). Flushing occurred in 3% patients, but none felt it to be troublesome. CONCLUSION: Adding ER niacin to atorvastatin exhibited beneficial effects on lipid profile with significant elevation of HDL-C cholesterol and further lowering of LDL-C compared to monotherapy. This treatment offered better targeted therapy and was well tolerated with proper monitoring in Indian patients.