Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review / Patogênese, achados histopatológicos e modalidades de tratamento da glomerulopatia por lipoproteínas: Uma revisão

Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.

Experiencia en la utilización de hipolipemiantes en una cohorte de pacientes en 12 ciudades colombianas / Experience in the use of oral lipid-lowering medicines in a group of patients followed in 12 colombian cities

Resumen Introducción: Los estudios de utilización de medicamentos sirven para evaluar la efectividad y seguridad de los fármacos en la práctica real, diferente al contexto del estudio clínico controlado. Los hipolipemiantes actúan sobre el perfil lipídico disminuyendo el riesgo de enfermedades cardiovasculares. Objetivo: Describir el desempeño clínico y seguridad de la utilización de medicamentos hipolipemiantes en la práctica médica real en una cohorte de pacientes con diagnóstico de dislipidemia. Metodología: Estudio observacional de cohorte. Se siguió una cohorte de pacientes con indicación de hipolipemiantes durante 6 meses, en 12 ciudades de Colombia pertenecientes a un registro biomédico de seguimiento de pacientes tratados con medicamentos del portafolio de Abbott. Se midieron variables demográficas y clínicas basales, de seguridad y de desempeño clínico de los medicamentos sobre el perfil lipídico a los 3 y 6 meses. Resultados: Se siguieron 501 pacientes en tratamiento con hipolipemiantes. Las estatinas solas disminuyeron el colesterol de baja densidad de 249 mg/ dL (RIQ=226-268) en la medición basal a 190 (177.6-210) y 170 (108-170) en la segunda y tercera medición, respectivamente. Para estatina + ezetimibe, de 167 mg/dL (RIQ=139-184) a 132 (110-150) y 128.5 (101.5-128.5). El fenofibrato disminuyó los triglicéridos de 275 mg/dL (RIQ=21çj-346) a 201 (172-239) y 150.5 (140-150.5). Conclusiones: la administración de estatinas sola o en combinación disminuyó los niveles de LDL y colesterol total, mientras que el fenofibrato demostró su efectividad al disminuir los triglicéridos. No se reportaron efectos adversos. Hubo una adherencia parcial del médico tratante a la guía de práctica clínica para dislipidemias. MÉD.UIS.2019;32(1):13-20.

Abstract Introduction: Drug use studies are important to evaluate the effectiveness and safety of drugs in daily practice, outside the controlled clinical study. Lipid-lowering drugs act on the lipid profile, decreasing the risk of cardiovascular diseases. Objective: To describe the clinical performance and safety of the use of lipid-lowering drugs in real practice in a group of patients diagnosed with dyslipidemia. Methods: An observational, descriptive cohort study. A cohort of patients with hypolipidemic indication for 6 months was followed in 12 cities of Colombia that belong to the biomedical registry of follow-up of patients treated with medicines from the Abbott portfolio. Baseline demographic and clinical variables, safety and efectivity of the drugs were measured on the lipid profile at 3 and 6 months. Results: 501 patients received lipid-lowering agents. Statins alone decreased the low density (LDL) cholesterol of 249 mg / dL (RIQ = 226-268) at baseline to 190 (177.6-210) and 170 (108-170) at the second and third measurements, respectively. For statin + ezetimibe, from 167 mg / dL (RIQ = 139-184) to 132 (110-150) and 128.5 (101.5-128.5). Fenofibrate decreased triglycerides from 275 mg / dL (RIQ = 219-346) to 201 (172-239) and 150.5 (140-150.5). Conclusions: The administration of statins alone or in combination decreased LDL and total cholesterol levels, while fenofibrate demonstrated its effectiveness in lowering triglycerides. No adverse effects were reported. There was partial adherence of the treating physician to GPC for dyslipidemias. There were no adverse events. MÉD.UIS.2019;32(1):13-20.

Enfermedad renal crónica, hiperparatiroidismo y vitamina D / Chronic kidney disease, hyperparathyroidism and vitamin D

El hiperparatiroidismo secundario (HTP2) es una complicación común de la enfermedad renal crónica (ERC). La consecuencia más frecuente del HTP2 es la enfermedad ósea, pero cabe destacar que niveles elevados de PTH guardan relación directa con enfermedades extra óseas. En pacientes con diabetes y enfermedad renal debe realizarse el seguimiento y control para evitar complicaciones del metabolismo fosfocálcico y disminuir el riesgo de anemia y enfermedad cardiovascular. Los movimientos iónicos pueden observarse en etapas tempranas de la ERC. Se recomienda la medición de calcio, fósforo, PTH, FAL y vitamina D a partir de un FG

Impact of roux-en-y gastric bypass surgery (rygb) on metabolic syndrome components and on the use of associated drugs in obese patients / Impacto do bypass gástrico em Y de Roux (RYGB) nos componentes da síndrome metabólica e sobre o uso de drogas associadas em pacientes obesos

ABSTRACT BACKGROUND The prevalence of obesity and metabolic syndrome is increasing worldwide and both behavior modification and drug therapy have low adherence. Gastric bypass has shown effective results in both reducing weight and improving comorbidities. OBJECTIVE To evaluate the impact of Roux-en-Y Gastric Bypass Surgery (RYGB) on both metabolic syndrome components and the use of associated drugs in obese patients. METHODS Historical cohort of patients subjected to Roux-en-Y Gastric Bypass Surgery (RYGB) between January 2007 and March 2014 in a private clinic. The sample consisted of 273 obese class II and III individuals, 86.4% of whom were female, with age ≥20 years, followed up for 2 months after surgery. Sociodemographic, anthropometric, biochemical, clinical, and drug-use data were collected from patients’ medical records. RESULTS Significant differences were found in weight, body mass index and waist circumference, after 60 postoperative days. Components for metabolic syndrome diagnosis (hypertension P=0.001; hyperglycemia P<0.001; hypertriglyceridemia P=0.006) were reduced after 60 days of postoperative, with the exception HDL-c (P=0.083). There was a significant reduction in the use of antihypertensive (P<0.001), hypoglycemic (P=0.013), lipid lowering (P<0.001), and antiobesity (P=0.010) drugs and increased use of gastroprotective drugs, vitamins, and minerals (P<0.001) after 60 postoperative days. CONCLUSION Patients subjected to Roux-en-Y Gastric Bypass Surgery exhibited both weight loss and significant improvement not only in metabolic syndrome components (except for HDL-c) but in the use of drugs associated with obesity and metabolic syndrome.

RESUMO CONTEXTO A prevalência de obesidade e síndrome metabólica é crescente no mundo e tanto a terapia de modificação de estilo de vida quanto a medicamentosa têm baixa adesão. O bypass gástrico tem apresentado resultados eficazes na redução de peso e comorbidades. OBJETIVO Avaliar o impacto do bypass gástrico em Y de Roux nos componentes da síndrome metabólica e sobre o uso de drogas associadas em pacientes obesos. MÉTODOS Coorte histórica de pacientes submetidos ao bypass gástrico em Y de Roux entre janeiro de 2007 e março de 2014, em clínica privada. A amostra foi composta por 273 indivíduos obesos classe II e III, 86,4% dos quais eram do sexo feminino, idade ≥20 anos, acompanhados por 2 meses após a cirurgia. Dados sociodemográficos, antropométricos, bioquímicos, clínicos e de uso de medicamentos foram coletados nos prontuários dos pacientes. RESULTADOS Foram encontradas diferenças significativas no peso, índice de massa corporal e circunferência da cintura, após 60 dias de pós-operatório. Os componentes para diagnóstico da síndrome metabólica (hipertensão P=0,001; hiperglicemia P<0,001; hipertrigliceridemia P=0,006) foram reduzidos no pós-operatório, com exceção do HDL-c (P=0,083). Houve uma redução significativa no uso de medicamentos anti-hipertensivos (P<0,001), hipoglicêmicos (P=0,013), hipolipemiantes (P<0,001), antiobesidade (P=0,010) e uma maior utilização de gastroprotectores, vitaminas e minerais (P<0,001) após 60 dias de pós-operatório. CONCLUSÃO Os pacientes submetidos ao bypass gástrico em Y de Roux exibiram perda de peso e uma melhora significativa, não só em componentes da síndrome metabólica (exceto para o HDL-c), mas também no uso de medicamentos associados à obesidade e à síndrome metabólica.

Estatinas en enfermedad renal crónica / Statins in chronic kidney disease

La enfermedad renal crónica constituye una patología de prevalencia e impacto creciente en la población mundial por sus múltiples complicaciones, incluyendo un riesgo cardiovascular aumentado, que representa la principal causa de morbimortalidad en pacientes nefrópatas crónicos. Sin embargo, la relevancia de las dislipidemias, especialmente, la hipercolesterolemia LDL, en el deterioro de la función renal y desarrollo de ateroesclerosis en sujetos con daño renal crónico no ha sido claramente establecida. Esta situación ha generado controversia sobre el beneficio real del uso de hipolipemiantes en estos pacientes. En base a la evidencia disponible, incluyendo estudios clínicos recientes, la recomendación más apropiada sugiere que el uso de terapia hipolipemiante basada en estatinas (con o sin ezetimiba) es beneficioso desde un punto de vista cardiovascular en nefrópatas crónicos con insuficiencia renal leve a moderada antes de la diálisis. Por otro lado, no existe evidencia definitiva para apoyar el uso rutinario de este tipo de hipolipemiantes en el manejo del deterioro de la filtración glomerular y/o la proteinuria. Basándose en la evidencia analizada en esta revisión, las futuras guías clínicas para el manejo del daño renal crónico deberán incorporar el uso de estatinas y/o ezetimiba como un elemento más dentro del armamento terapéutico de este tipo de pacientes.(AU)

Chronic kidney disease is a condition of increasing prevalence and impact on the world population by its many complications, including increased cardiovascular risk that represents the leading cause of morbidity and mortality in chronic nephropathy patients. However, the relevance of dyslipidemia, especially high LDL cholesterol, in the impairment of renal function and development of atherosclerosis in subjects with chronic kidney disease has not been clearly established. This situation has generated controversy regarding the real benefit of use of lipid-lowering therapy in these patients. Based on available evidence, including recent clinical studies, the most appropriate recommendation suggests that the use of lipid-lowering therapy based on statins (with or without ezetimibe) is beneficial from a cardiovascular standpoint in chronic nephropathy with mild to moderate renal failure before dialysis. On the other hand, there is no definitive evidence to support the routine use of lipid lowering drugs in the management of impaired glomerular filtration and/or proteinuria. Based on the evidence discussed in this review, future clinical guidelines for management of chronic renal damage should incorporate the use of statins and/or ezetimibe as a key element in the therapeutic armamentarium to be applied in these patients.(AU)

Dislipidemia em pacientes com doença renal crônica / Dyslipidemia in patients with chronic kidney disease

JUSTIFICATIVA E OBJETIVOS: Identificar o perfil lipídico dos pacientes renais crônicos e analisar a prevalência das alterações lipídicas nesses pacientes. MÉTODOS: Realizado um estudo retrospectivo em 136 pacientes portadores de doença renal crônica (DRC) não dialítica atendidos em um único ambulatório. Foram coletados os seguintes dados: sexo, idade, comorbidades, medicações em uso, exame físico e exames laboratoriais. Calculou-se a prevalência das principais dislipidemias e as variáveis foram analisadas por meio das estatísticas descritivas: média aritmética e mediana. Foram utilizados os testes t de Student, Mann-Whitney, qui-quadrado e Exato de Fisher. As variáveis foram comparadas entre os grupos com e sem dislipidemia. RESULTADOS: A prevalência de dislipidemias foi de 75,7%, sendo a média dos valores de colesterol total (CT) de 179,6±41,0mg/dl, HDL-colesterol de 46,1±12,6mg/dl,LDL-colesterol de 101,7±34,5mg/dl e de triglicerídeos de 160,0±87,2mg/dl. O grupo com dislipidemia apresentou níveis superiores de triglicerídeos e inferiores de HDL-colesterol. CONCLUSÕES: Observamos elevada prevalência de dislipidemia neste estudo.

BACKGROUND AND OBJECTIVES: Identify the lipid profile of chronic renal patients and the prevalence of lipid disorders in these patients. METHODS: A retrospective study was performed in 136 patients with chronic kidney diseases (CKD) not dialytic, treated in a unique clinic. The following data were collected: gender, age, comorbidities, medications in use, physical examination and laboratory tests. It has been estimated the prevalence of dyslipidemias and main variables were analyzed through descriptive statistics: arithmetic mean and median. The Student's t-tests, Mann-Whitney, chi-squareand Fisher exact were used. Variables were compared between groups with and without dyslipidemia. RESULTS: The prevalence of dyslipidemias was 75.7%, with an average of the total cholesterol of 179.6±41.0mg/dl, HDL-cholesterol of 46.1±12.6mg/dl, LDL cholesterol of 101.7±34.5mg/dl and triglyceride levels of 160.0±87.2mg/dl. The group with dyslipidemia showed increased levels of triglycerides and lower HDL cholesterol. CONCLUSIONS: We observed a high prevalence of dyslipidemia in this study.

Tratamento otimizado antiplaquetário, antilipêmico, controle de pressão arterial e frequência cardíaca na doença coronariana crônica assintomática ou angina classe I / Optimized antiplatelet and hypolipidemic treatment, control of blood pressure and heart rate in chronic asymptomatic coronary artery disease or angina class 1

Neste artigo revisaremos o tratamento antiplaquetário e antilipêmico, controle da pressão arterial e controle da frequência cardíaca e sua influência na mortalidade e novos eventos, aplicável a todo paciente portador de doença coronariana crônica.

We review the antiplatelet and hypolipidemic treatment, blood pressure and heart rate control and its influence on mortality and new events, applicable to all patients with chronic coronary disease.

Effectiveness of lipid-lowering therapy among a sample of patients in Colombia / Eficacia del tratamiento hipolipemiante en una muestra de pacientes de Colombia

OBJECTIVE: To determine the effectiveness of lipid-lowering therapy in a sample of patients affiliated with the Sistema General de Seguridad Social en Salud (the Colombian health system). METHODS: A cross-sectional study was conducted from 1 January 2010-30 June 2011. From a total of 8 316 patients in 10 cities, a random sample of 600 was stratified according to dyslipidemia. Information on sociodemographic and anthropometric characteristics, risk factors, and pharmacological and laboratory variables were obtained from medical records. RESULTS: Subjects were predominantly female (56.2%), with a mean age of 65.1 ± 11.5 years; 93.2% had hypertension; 29.0%, diabetes mellitus; and 10.2%, a history of myocardial infarction. The patients were being treated with lovastatin (84.1%) or gemfibrozil (12.3%)-both at doses below what is recommended-or atorvastatin (1.8%). In patients with high cardiovascular risk, 38.6% achieved goals for low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL). Among those at moderate risk, 49.4% reached the target level (< 130 mg/dL). On average, there was a 4.9% reduction in LDL-C. Sex, age, history of cardiovascular disease and/or diabetes mellitus, use of hydrochlorothiazide, and poor therapy adherence were statistically associated with a lack of dyslipidemia control. CONCLUSIONS: Because a lack LDL-C control occurred in patients with two or more of the following variables: male, more than 55 years of age, diabetes and/or a history of cardiovascular disease, received lower doses of lovastatin, or non-adherent to treatment, it is recommended that medication be increased based on clearly-defined therapeutic goals and that comorbidities be assessed and effectively treated.

OBJETIVO: Determinar la eficacia del tratamiento hipolipemiante en una muestra de pacientes afiliados al Sistema General de Seguridad Social en Salud de Colombia. MÉTODOS: Se llevó a cabo un estudio transversal desde el 1 de enero del 2010 al 30 de junio del 2011. De un total de 8 316 pacientes de 10 ciudades seleccionadas, se estratificó una muestra aleatoria de 600 pacientes en función de la dislipidemia. A partir de los expedientes médicos, se obtuvo información sobre las características sociodemográficas y antropométricas, los factores de riesgo y las variables farmacológicas y de laboratorio. RESULTADOS: En la muestra predominaban las mujeres (56,2%) y la media de la edad era de 65,1 ± 11,5 años; 93,2% de los pacientes eran hipertensos; 29,0% eran diabéticos; y 10,2% tenían antecedentes de infarto de miocardio. Los pacientes recibían tratamiento con lovastatina (84,1%) o gemfibrozilo (12,3%) -ambos a dosis inferiores a las recomendadas- o atorvastatina (1,8%). El 38,6% de los pacientes con alto riesgo de enfermedad cardiovascular alcanzaron los objetivos de reducción de los niveles de colesterol unido a lipoproteínas de baja densidad (C-LDL) (< 100 mg/dL). El 49,4% de los pacientes que presentaban un riesgo moderado también alcanzaron los niveles fijados como objetivo (< 130 mg/dL). En promedio, hubo una reducción de 4,9% del C-LDL. El sexo, la edad, los antecedentes personales de enfermedad cardiovascular y diabetes, la administración de hidroclorotiazida y la deficiente adherencia al tratamiento se asociaron estadísticamente con una falta de control de la dislipidemia. CONCLUSIONES: Dado que se produjo un control deficitario del C-LDL en pacientes con dos o más de las siguientes variables: varones, mayores de 55 años, diabéticos o con antecedentes de enfermedad cardiovascular, que recibían dosis bajas de lovastatina, o mostraban falta de adherencia al tratamiento, se recomienda que se aumente la medicación con base en objetivos terapéuticos claramente definidos y que se evalúen y se traten eficazmente las comorbilidades.

Prevalencia de dislipemia y riesgo cardiovascular elevado en pacientes con artritis reumatoide / Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid arthritis

Los objetivos del estudio fueron comparar la frecuencia de riesgo cardiovascular (CV) elevado y dislipemia (DLP) en pacientes con artritis reumatoide (AR) y en controles, identificar variables de la enfermedad asociadas a DLP y estimar el porcentaje de pacientes con AR medicados para DLP. Estudio de corte transversal que incluyó 409 pacientes con AR y 624 controles. El riesgo CV se determinó con las clasificaciones NCEP y SCORE modificados por European League Against Rheumatism (EULAR). Para DLP se utilizó la definición de Adult Treatment Panel III (ATP III). La frecuencia de riesgo CV elevado fue similar en pacientes con AR y controles excepto cuando fue definida por NCEP-EULAR (7% vs. 2%; p = 0.00002). La DLP fue encontrada en el 43% de los pacientes con AR y en el 47% de los controles (p = 0.15). Los pacientes con AR y DLP tuvieron más manifestaciones extra-articulares (36% vs. 24%; p = 0.01) y mayor velocidad de sedimentación globular (VSG) (21 (13-35) vs. 18 (10-30) mm; p = 0.003). El tratamiento recibido para DLP varió según la definición utilizada (11% a 32%). Se encontró mayor riesgo CV en los pacientes con AR solo cuando se definió por NCEP- EULAR. Los pacientes con AR y DLP tuvieron mayor VSG y manifestaciones extra-articulares. La mayoría de los pacientes con AR y DLP no estaban recibiendo tratamiento hipolipemiante.

The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.

Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system / Prevención de la enfermedad cardiovascular basada en tratamiento hipolipemiante: un reto para el sistema de salud de México

OBJECTIVE: To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS: Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. RESULTS: A cardiovascular risk equivalent was found in 13.8 percent and >2 risk factors were present in 31.5 percent of the population. LDL-C concentrations were above the treatment goal in 70 percent of the high-risk group and in 38.6 percent of subjects with >2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. CONCLUSIONS: Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25 percent, drug therapy in 24.19 percent).

OBJETIVO: Calcular el porcentaje de adultos que requiere tratamiento hipolipemiante de acuerdo con las recomendaciones del Programa Nacional de Educación en Colesterol-III, usando los datos de la Encuesta Nacional de Salud y Nutrición 2006. MATERIAL Y MÉTODOS: Se incluyeron 4040 individuos con edad entre 20 y 69 años estudiados bajo un ayuno de 9 a 12 horas. RESULTADOS: Un equivalente de enfermedad cardiovascular fue identificado en 13.8 por ciento de los participantes. El 31.5 por ciento de la población tenía >2 factores de riesgo cardiovascular. La concentración de colesterol LDL estuvo arriba de la meta terapéutica en 70 por ciento de los casos con alto riesgo cardiovascular y en el 38.6 por ciento de los sujetos con >2 factores de riesgo. Cerca de 12 millones de mexicanos deben modificar su estilo de vida para reducir su concentración de colesterol LDL. Casi 8 millones califican para recibir tratamiento farmacológico. CONCLUSIONES: Una tercera parte de los adultos requiere alguna forma de tratamiento hipolipemiante (cambios en el estilo de vida: 36.25 por ciento, medicamentos: 24.19 por ciento).

Fenofibrate-induced rhabdomyolysis in a patient with chronic kidney disease: an unusual presenting feature of hypothyroidism / Rabdomiólise induzida por fenofibrato em paciente com doença renal crônica: uma apresentação clínica incomum do hipotireoidismo

Clinical and most often moderate skeletal muscle involvement is a frequent problem in adults with hypothyroidism, and includes a number of different manifestations. Severe involvement with rhabdomyolysis, however, is very rare, and only a few cases have been reported to date, most of them with an additional factor of muscle injury. We described a patient with stage 3 chronic kidney disease who presented with rhabdomyolysis while taking fenofibrate, and was found to have hypothyroidism. We also highlighted the importance of excluding the diagnosis of thyroid dysfunction before treatment with lipid-lowering agents.

Manifestações musculoesqueléticas variadas e de moderada intensidade são comuns em adultos com hipotireoidismo. No entanto, o envolvimento muscular grave, caracterizado por rabdomiólise, é incomum. Até o momento, poucos casos foram descritos na literatura, e a maior parte deles em associação com um fator adicional de dano muscular. Descrevemos um paciente com doença renal crônica (estádio 3) que se apresentou com rabdomiólise durante o tratamento com fenofibrato e cuja investigação adicional evidenciou hipotireoidismo primário. Enfatizamos, ainda, a importância da exclusão de disfunção tireoidiana antes de iniciar terapia com agentes hipolipemiantes.

Análise do perfil lipídico de mulheres idosas em Curitiba - Paraná / Analysis of the lipid profile of elderly woman in Curitiba - Parana

FUNDAMENTO: A dislipidemia é considerada um dos principais fatores de risco para a doença cardiovascular, que, por sua vez, é mais freqüente em indivíduos de idade avançada. Contudo, evidências sugerem que uma parcela da população idosa desconhece a característica de seu perfil lipídico, assim como muitos não possuem acesso a um tratamento adequado. OBJETIVO: Analisar o perfil lipídico e a freqüência da utilização da terapia hipolipemiante de mulheres idosas em Curitiba - Paraná. MÉTODOS: A amostra foi composta por 312 mulheres (idade média 68,8; desvio padrão 6,0 anos). O perfil lipídico foi determinado por meio das dosagens de colesterol total (CT), colesterol de lipoproteína de alta densidade (HDL-C), colesterol de lipoproteína de baixa densidade (LDL-C) e triglicerídeos (TG). A utilização da terapia hipolipemiante foi verificada por meio de auto-relato, em seguida os grupos foram divididos em dois subgrupos, satisfatório e insatisfatório. RESULTADOS: Foi encontrada uma grande prevalência de indivíduos com valores insatisfatórios nos componentes do perfil lipídico, no grupo que relatou não estar sob terapia hipolipemiante: 74,2 por cento das mulheres portadoras de doenças cardiovasculares (DCV) apresentaram valores superiores à meta lipêmica para o LDL-C (<100,0 mg/dl). Por sua vez, 45,8 por cento a 49,3 por cento dos indivíduos do grupo que relatou utilizar medicamento hipolipemiante apresentaram valores insatisfatórios para CT, TG e LDL-C, e 25,4 por cento obtiveram valores de HDL-C inferiores a 40,0 mg/dl. CONCLUSÃO: Os resultados desta investigação indicam uma alta prevalência de mulheres idosas, independentemente do auto-relato de utilizar terapia hipolipemiante, com o perfil lipídico desfavorável, principalmente em relação à meta lipêmica para o LDL-C nas mulheres idosas portadoras de DCV.

BACKGROUND: Dyslipidemia is considered one of the main risk factors for cardiovascular disease (CVD), which is more frequent in older individuals. However, evidence suggests that a large number of elderly individuals is not aware of their lipid profile status; additionally, many of them do not have access to adequate treatment. OBJECTIVE: To analyze the lipid profile and the frequency of lipid-lowering therapy use in elderly women from the city of Curitiba, state of Parana, Brazil. METHODS: The sample consisted of 312 women (mean age = 68.8; SD = 6.0 years). The lipid profile was determined by plasma levels of total cholesterol (TC), high-density cholesterol (HDL-C), low-density cholesterol (LDL-C) and triglycerides (TG). The number of subjects that reported being on lipid-lowering therapy was self-reported; therefore, the groups were divided into two subgroups, satisfactory and unsatisfactory. RESULTS: A high prevalence of individuals with unsatisfactory levels of lipid profile components was observed in the group that self-reported not being on lipid-lowering therapy; of these, 74.2 percent of women with CVD presented levels above the LDL-C goal. On the other hand, 45.8 to 49.3 percent of the individuals from the group that self-reported being on lipid-lowering therapy had unsatisfactory values of TC, TG and LDL-C, and 25.4 percent had HDL-C levels lower than 40.0 mg/dl. CONCLUSION: The results of this investigation indicate a high prevalence of elderly women, regardless of self-reports of being on lipid-lowering therapy, with an unsatisfactory lipid profile, mainly related to LDL-C goal for those individuals with CVD.

Isquemia silenciosa na doença coronariana estável em vigência de tratamento medicamentoso / Silent myocardial ischemia in patients with stable coronary artery disease receiving conventional antianginal drug therapy

FUNDAMENTO: Existem poucos dados sobre comportamento da isquemia miocárdica às atividades habituais na vigência da medicação em pacientes com doença coronariana. OBJETIVO: Estudar mecanismo gerador da isquemia miocárdica avaliando-se o comportamento da pressão arterial e da freqüência cardíaca em pacientes com doença aterosclerótica estável, medicados e com evidência de isquemia. MÉTODOS: Cinqüenta pacientes (40 homens) realizaram ambulatorialmente por 24 horas a monitorização eletrocardiográfica sincronizada com a monitorização da pressão arterial. RESULTADOS: Em 17 pacientes detectaram-se 35 episódios de isquemia miocárdica, com duração total de 146,3 minutos, ocorrendo relato de angina em cinco casos. Houve 29 episódios (100,3 minutos) durante o período de vigília, com 11 episódios (35,3+3,7 min) no período das 11 às 15 horas. A avaliação da pressão arterial e freqüência cardíaca nos três intervalos de 10 minutos posteriores ao momento de isquemia mostrou diferença estatisticamente significante (p<0,05), o que não ocorreu nos três intervalos anteriores. Entretanto, durante o momento isquêmico, percebeu-se elevação maior que 10 mmHg da pressão arterial e de cinco batimentos por minuto da freqüência cardíaca quando comparado ao intervalo de tempo entre 20 e 10 minutos anterior. A freqüência cardíaca média no início da isquemia durante teste ergométrico prévio ao estudo foi de 118,2+14,0, e de 81,1+20,8 batimentos por minuto na eletrocardiografia de 24 horas (p<0,001). CONCLUSÃO: A incidência de isquemia silenciosa é freqüente na doença coronária estável, relacionando-se com alterações da pressão arterial e da freqüência cardíaca, com diferentes limiares de isquemia para o mesmo paciente.

BACKGROUND: Few data are available on the behavior of myocardial ischemia during daily activities in patients with coronary artery disease receiving antianginal drug therapy. OBJECTIVE: To study the mechanism generating myocardial ischemia by evaluating blood pressure and heart rate changes in patients with stable atherosclerotic disease receiving drug therapy and with evidence of myocardial ischemia. METHODS: Fifty non-hospitalized patients (40 males) underwent 24-hour electrocardiographic monitoring synchronized with blood pressured monitoring. RESULTS: Thirty five episodes of myocardial ischemia were detected in 17 patients, with a total duration of 146.3 minutes; angina was reported in five cases. Twenty nine episodes (100.3 minutes) occurred during wakefulness, with 11 episodes (35.3 + 3.7 min) in the period from 11 a.m. to 3 p.m. Blood pressure and heart rate evaluation in the three ten-minute intervals following the ischemic episodes showed a statistically significant difference (p< 0.05), unlike that shown for the three intervals preceding the episodes. However, during the ischemic episode, a higher than 10-mmHg elevation in blood pressure and 5 beats per minute in heart rate were observed when compared with the time interval between 20 and 10 minutes before the episode. The mean heart rate at the onset of ischemia during the exercise test performed before the study was 118.2 + 14.0, and 81.1 + 20.8 beats per minute on the 24-hour electrocardiogram (p < 0.001). CONCLUSION: The incidence of silent myocardial ischemia is high in stable coronary artery disease and is related to alterations in blood pressure and heart rate, with different thresholds for ischemia for the same patient.

Fibrinógeno. Factor o indicador de riesgo cardiovascular? / Fibrinogen. Cardiovascular risk factor or marker?

Endothelial dysfunction and inflammation play a crucial role in all stages of atherosclerosis, from the beginning, during progression, and, finally, in its highest clinical expression: acute coronary syndromes. In this process, fibrinogen, an acute phase reactant with active participation in endothelial function, thrombosis and inflammation has proved to be an independent variable to cardiovascular risk together with its participation in resistance phenomena to different antithrombotic approaches. The reasons by which fibrinogen is elevated in cardiovascular disease and atherosclerosis are, in general, only incompletely understood; but all cells involved in the atherogenetic process are able to produce cytokines, which induce an acute phase reaction that increases fibrinogen levels in plasma. The potential pathophysiological mechanisms by which elevated fibrinogen levels mediate cardiovascular risk are multiple. Fibrinogen forms the substrate for thrombin an represents the final step in the coagulation cascade, it is essential for platelet aggregation, it modulates endothelial function, it promotes smooth muscle cell proliferation and migration, it interacts with the binding of plasmin with its receptor and, finally, it represents a major acute phase protein. Epidemiological studies have established sufficient evidence to consider fibrinogen as a strong, consistent, and independent cardiovascular risk marker or factor. Based on all these implications, the target of this review is an analysis of physiopathogenic and epidemiologic evidence searching for guidelines to establish whether fibrinogen as a risk factor or marker is the lost link between cardiovascular disease and classic risk factors. CONCLUSION: Analyses of the respective studies suggest that fibrinogen is an important and independent cardiovascular risk factor, clearly associated with conventional risk factors and genetic polymorphisms. Whether or not fibrinogen is causally involved in atherothrombogenesis still remains to be determined and despite of unsolved issues that are waiting conclusive answers, fibrinogen has emerged as an important additional marker of cardiovascular risk.

Perfil nutricional e lipídico de mulheres na pós-menopausa com doença arterial coronariana / Nutritional status and lipid profile of postmenopausal women with coronary heart disease

OBJETIVO: Avaliar o estado nutricional e perfil lipídico de mulheres na pós-menopausa com doença arterial coronariana. MÉTODOS: Estudo transversal retrospectivo de dados obtidos do prontuário médico de 217 mulheres, na ocasião da 1° consulta no Ambulatório de Nutrição do InCor, referentes ao estado nutricional, pelo índice de massa corpórea, uso de medicamentos hipolipemiantes e lípides plasmáticos (colesterol e frações). RESULTADOS: A média de idade foi 60,98 ± 9,23 anos com prevalência de obesidade em 56 por cento. O uso de medicamentos hipolipemiantes foi observado em 73 por cento da população. Quanto ao perfil lipídico, 56 por cento apresentavam níveis plasmáticos adequados de HDL-c. O estado nutricional esteve inadequado devido à prevalência de obesidade, o que implica no surgimento de outras doenças crônicas, como as dislipidemias. Embora não se tenha verificado a dosagem utilizada, o emprego de hipolipemiantes pela população estudada não pareceu ser favorável, pois foram observados níveis elevados de colesterol total e LDL-c, que nessa condição, encontram-se fortemente relacionados à ocorrência de doenças cardiovasculares. CONCLUSÃO: Faz-se necessária a ação multidisciplinar em programas de Saúde da Mulher, abrangendo aspectos preventivos relacionados à doença arterial coronariana para, assim, melhorar a qualidade de vida nessa população.

Dislipidemia en el anciano / Dyslipidemia in the Elderly

La edad es un factor de riesgo independiente e inmodificable para enfermedad coronaria. En México, alrededor del 50% de las muertes que ocurren después de los 65 años de edad son debidas a cardiopatía isquémica. La senectud produce importantes diferencias en la presentación, en el diagnóstico, en el pronóstico y en la respuesta a la terapia. La meta fundamental en el tratamiento de la enfermedad arterial coronaria es la prolongación de la vida y la mejoría en la calidad de la misma. En el grupo de ancianos, lo más importante será elevar su calidad de vida con el objetivo primordial de favorecer la autosuficiencia. La disminución en los niveles de lípidos séricos se asocia con una reducción en la incidencia de cardiopatía isquémica independiente de la edad. El tratamiento deberá inicialmente constar de una prescripción dietética individualizada y modificación del estilo de vida. Cuando esto es insuficiente para lograr los niveles deseados de lípidos, el tratamiento de elección es la administración de estatinas. Cuando los triglicéridos están elevados y el C-HDL es bajo, la indicación será para fibratos. El beneficio absoluto es mayor en los enfermos de edades más avanzadas, reduciendo el riesgo de eventos cardiovasculares que puedan afectar su independencia y su calidad de vida.

Age is an independent and unmodifiable risk factor for coronary atherosclerosis. In Mexico, coronary heart disease is responsible for 50 % of the deaths for those older than 65 years of age. Aging produces major differences in the presentation, diagnosis, prognosis, and response to therapy in coronary heart disease. The goal of treatment is the prolongation of survival and the improvement of the quality of life. However, in the elderly, the aim of therapy should focus on attaining a meaningful quality of life thus allowing them to be functionally independent. Clinical trials demonstrate conclusively that lowering serum cholesterol levels will reduce the incidence of coronary heart disease irrespective of age. Dietary advise and lifestyle modifications are the first-line approach in the elderly. When these measures are insufficient to achieve target lipid reductions, statins are the drug of choice. Fibrates may be indicated if triglycerides are high and C-HDL is low. Given the grater coronary risk of older population, the absolute benefit will be greater in the elderly.

Eficácia da associação Metotrexato e Cloroquina no tratamento da artrite induzida por adjuvante / Effectiveness of the association Methotrexate and Chloroquine in the treatment of the induced arthritis for adjuvant

A artrite reumatóide (AR) é uma doença inflamatória crônica, de natureza autoimune, caracterizada pela infiltração e ativação de células inflamatórias no tecido sinovial de múltiplas articulações. O metotrexato (MTX) é muito utilizado na terapia da AR, apresentando atividade antiinflamatória e imunomoduladora, atuando sobre a proliferação celular na sinóvia e inibindo a migração de leucócitos e a produção de radicais superóxidos. Assim, o objetivo deste trabalho foi realizar um estudo sistemático dos efeitos do MTX, da CQ e da associação MTX+CQ sobre a resposta inflamatória, e sobre a atividade de enzimas (fosfatases e transaminases) no plasma e no fígado de ratos, utilizando o modelo da artrite induzida por adjuvante. A artrite foi induzida em ratos Holtzman pela injeção intradérmica de 0,1 mL da suspensão de M. tuberculosis em óleo mineral em uma das patas posteriores do animal. O desenvolvimento da resposta inflamatória (edema das patas posteriores e anteriores, aparecimento de nódulos na cauda e nas orelhas, perfil hematológico e evolução do peso corporal) foi avaliado por um período de 21 dias. Grupos de animais foram tratados com: a) MTX, administrado semanalmente, via intraperitonial, nas doses de 0,15; 1,5; 3; 6 e 12 mg/Kg; b) CQ, administrada por via intragástrica, diariamente, nas doses de 25 e 50 mg/Kg e c) associação MTX+CQ, administrada em duas combinações diferentes (MTX1,5 mg/kg+CQ50 mg/Kg e MTX6 mg/kg+CQ50 mg/Kg). Os tratamentos foram iniciados no mesmo dia da indução da artrite. No final do período experimental, os animais foram anestesiados e o sangue e o fígado coletados e preparados para as determinações bioquímicas. A atividade de fosfatases (ácida e alcalina) e de transaminases (aspartato amino transferase e alanina amino transferase) no plasma e no fígado foram determinadas, assim como a concentração plasmática de creatinina. Os resultados obtidos neste estudo mostraram que o MTX nas doses de 6 e 12 mg/Kg reduziu...

Prescriçäo e aderência das estatinas em pacientes com doença arterial coronariana e hipercolesterolemia / Prescription and adherence to statins of patients with coronary artery disease and hypercholesterolemia

OBJECTIVE: Statins have proved to be safe and effective in the secondary prevention of coronary artery disease, but the level of prescription and the reasons for nonadherence to treatment in many coronariopathy treatment centers has not been determined. The purpose of this study was to identify reasons for nonadherence to statin therapy. METHODS: We analyzed 207 consecutive patients with coronary artery disease and hypercholesterolemia (total cholesterol > or = 200mg/dL or LDL - cholesterol > or = 130mg/dL). Patients' average age was 61.7 + or - 10 year; 111 (53.6 percent) male were and 94 (46.6 percent) were female. We analyzed the level of prescription and adherence to treatment with statins. RESULTS: Statins were prescribed for 139 (67 percent) patients, but only 85 (41 percent) used the drug. In spite of being indicated, statins were not prescribed in 68 (33 percent) patients. Of 54 (26 percent) patients, nonadherent to statins, 67 percent did not use the drug due to its high cost, 31 percent due to the lack of instruction, and only 2 percent due to side effects. Total cholesterol (260.3Ý42.2 vs 226.4 + or -51.9; p<0.0001) and LDL cholesterol (174.6 + or -38.1 vs 149.6 + or - 36.1; p<0.0001) were lower in patients on medication. HDL-cholesterol increased from 37.6 + or -9.6 to 41.5 + or -12.9mg/dL (p=0.02), and triglycerides were not modified in patients using statins. CONCLUSION: The prescription of statins in patients with coronary artery disease and dyslipidemia is high; however, its adherence is far from satisfactory, due to the high cost of the medication. Reduction in total cholesterol and LDL cholesterol levels did not reach the targets recommended by the Brazilian Consensus on Dyslipidemia