Carga económica de la hipercolesterolemia en población con alto riesgo cardiovascular en México / Economic burden of hypercholesterolemia in high risk of cardiovascular disease population in Mexico

Resumen Objetivo: Se estimó la carga económica directa e indirecta de la hipercolesterolemia en población con alto riesgo de presentar un evento cardiovascular. Para ello se definieron específicamente cinco grupos de pacientes: 1) aquellos con hipercolesterolemia familiar; 2, 3 y 4) personas con hipercolesterolemia más el antecedente de diabetes, infarto o evento vascular cerebral; 5) pacientes con hipercolesterolemia más diabetes y antecedente de infarto agudo de miocardio (definidos como pacientes de muy alto riesgo cardiovascular). Los cálculos se hicieron desde la perspectiva de las instituciones de salud pública en México. Método: Para la estimación de los costos directos se incluyó la atención ambulatoria, el tratamiento farmacológico, la atención hospitalaria y las intervenciones quirúrgicas relacionadas con las enfermedades cardiovasculares. Para la carga económica indirecta, se consideraron las muertes reportadas específicamente por causa de hipercolesterolemia, en un momento anterior al final de la edad productiva (muerte prematura). Resultados: La carga económica directa de las cinco categorías de pacientes en riesgo consideradas es de MXN $39,601,464,154 (USD $1,987,526,432), mientras que la carga económica indirecta asciende a MXN $121,646,689 (USD $6,105,229). Conclusiones: El impacto económico de la hipercolesterolemia en población con alto riesgo cardiovascular correspondía a $39,723,110,843 en 2020 (equivalente a USD $1,993,631,661), equivalente al 0.16% del PIB nacional.

Abstract Objective: To estimate the direct and indirect economic burden of hypercholesterolemia in patients with high risk of a cardiovascular event, specifically there were defined 5 groups of patients: 1) familial hypercholesterolemia; 2, 3 and 4) patients with hypercholesterolemia and background of diabetes, myocardial infarction or stroke; 5) diabetes, myocardial infarction and hypercholesterolemia (very high-risk patients) from the Mexican public healthcare institutions. Methods: For the estimation of the direct costs the items included correspond to: outpatient care, pharmacological treatment, inpatient hospital care, and surgical procedures. For indirect economic burden, death certificates, before the end of the productive age due to hypercholesterolemia were calculated (premature mortality). Results: The direct economic burden for the 5 groups of patients at risk is MXN $39,601,464,154 (USD $1,987,526,432), while the indirect economic burden amounts to MXN $121,646,689 (USD $6,105,229). Conclusions: The economic impact of hypercholesterolemia in patients with high cardiovascular risk is $39,723,110,843 (equivalent to USD $1,993,631,661) and corresponds to the 0.16% of GDP.

Tendencia del programa de intervención en DemoMinga, como estrategia para mejorar las dislipidemias y glucemia en la población Norma Luisa, Minga Guazú / Trend of the DemoMinga intervention program as a strategy to improve dyslipidemia and glycemia in the Norma Luisa population, Minga Guazú

Antecedentes: Las enfermedades no transmisibles siguen siendo un problema creciente en el mundo, sobre todo en los países de mediano y bajo ingresos. Los programas de intervención comunitaria se enfocan en su disminución mediante cambios en estilos de vida más saludables. Objetivos: Analizar la tendencia del programa de intervención en actividad física y nutrición, como estrategia para mejorar las dislipidemias y glucemia en los participantes del proyecto DemoMinga. Materiales y métodos: Estudio con enfoque cuantitativo. Diseño de investigación acción participativa, de carácter longitudinal, prospectivo. La población estuvo constituida por los participantes del Proyecto DemoMinga. Se determinó en cada participante: colesterol total, triglicéridos y glucemia en ayunas. Las muestras fueron procesadas en el Centro de Investigaciones Médicas de la FACISA-UNE. Se determinaron indicadores de tendencia central (mediana) de cada una de las variables. Resultados: Hubo mayor participación del sexo femenino, con predominio de personas con menos de 45 años. Las mediciones químicas arrojaron una tendencia de disminución a partir del quinto año de intervención, con talleres de cocina saludable incluyendo uso de aceite alto oleico, y actividad física. Sin embargo, la prueba no arrojó diferencias significativas de las mediciones entre la línea de base y el corte a los 6 años. Conclusión: El estudio resalta la importancia de los programas de intervención mediante terapias integrales para la promoción y prevención de las enfermedades cardiometabólicas a largo plazo.

Background: Non-communicable diseases remain a growing problem worldwide, especially in middle and low-income countries. Community intervention programs are focused on reducing their prevalence through promoting healthier lifestyle changes. Objectives: To analyze the trend of the physical activity and nutrition intervention program as a strategy to improve dyslipidemia and glycemia among participants of the DemoMinga project. Materials and methods: This study employed a quantitative approach with a participatory action research design, characterized as longitudinal and prospective. The population consisted of participants from the DemoMinga Project. For each participant, total cholesterol, triglycerides, and fasting glycemia were measured. Samples were processed at the Medical Research Center of FACISA-UNE. Indicators of central tendency (median) were determined for each of the variables. Results: There was a higher participation of females, with a predominance of individuals under the age of 45. Chemical measurements showed a decreasing trend starting from the fifth year of intervention, involving healthy cooking workshops that included the use of high oleic oil and physical activity. However, the test did not yield significant differences in measurements between the baseline and the 6-year cutoff. Conclusion: The study highlights the significance of intervention programs using comprehensive therapies for the long-term promotion and prevention of cardiometabolic diseases.

Tendencia del programa de intervención en DemoMinga, como estrategia para mejorar las dislipidemias y glucemia en la población Norma Luisa, Minga Guazú

Antecedentes: Las enfermedades no transmisibles siguen siendo un problema creciente en el mundo, sobre todo en los países de mediano y bajo ingresos. Los programas de intervención comunitaria se enfocan en su disminución mediante cambios en estilos de vida más saludables. Objetivos: Analizar la tendencia del programa de intervención en actividad física y nutrición, como estrategia para mejorar las dislipidemias y glucemia en los participantes del proyecto DemoMinga. Materiales y métodos: Estudio con enfoque cuantitativo. Diseño de investigación acción participativa, de carácter longitudinal, prospectivo. La población estuvo constituida por los participantes del Proyecto DemoMinga. Se determinó en cada participante: colesterol total, triglicéridos y glucemia en ayunas. Las muestras fueron procesadas en el Centro de Investigaciones Médicas de la FACISA-UNE. Se determinaron indicadores de tendencia central (mediana) de cada una de las variables. Resultados: Hubo mayor participación del sexo femenino, con predominio de personas con menos de 45 años. Las mediciones químicas arrojaron una tendencia de disminución a partir del quinto año de intervención, con talleres de cocina saludable incluyendo uso de aceite alto oleico, y actividad física. Sin embargo, la prueba no arrojó diferencias significativas de las mediciones entre la línea de base y el corte a los 6 años. Conclusión: El estudio resalta la importancia de los programas de intervención mediante terapias integrales para la promoción y prevención de las enfermedades cardiometabólicas a largo plazo.

Background: Non-communicable diseases remain a growing problem worldwide, especially in middle and low-income countries. Community intervention programs are focused on reducing their prevalence through promoting healthier lifestyle changes. Objectives: To analyze the trend of the physical activity and nutrition intervention program as a strategy to improve dyslipidemia and glycemia among participants of the DemoMinga project. Materials and methods: This study employed a quantitative approach with a participatory action research design, characterized as longitudinal and prospective. The population consisted of participants from the DemoMinga Project. For each participant, total cholesterol, triglycerides, and fasting glycemia were measured. Samples were processed at the Medical Research Center of FACISA-UNE. Indicators of central tendency (median) were determined for each of the variables. Results: There was a higher participation of females, with a predominance of individuals under the age of 45. Chemical measurements showed a decreasing trend starting from the fifth year of intervention, involving healthy cooking workshops that included the use of high oleic oil and physical activity. However, the test did not yield significant differences in measurements between the baseline and the 6-year cutoff. Conclusion: The study highlights the significance of intervention programs using comprehensive therapies for the long-term promotion and prevention of cardiometabolic diseases.

Xantelasma palpebral: tratamento cirúrgico como primeira escolha / Eyelid Xanthelasma: surgical treatment as the first choice

Introdução: O xantelasma palpebral é a forma mais comum de xantoma cutâneo, caracterizado por placas amareladas localizadas na pele das pálpebras. Apesar de ser uma condição benigna e não cursar com limitação funcional, é uma importante queixa estética que tem impacto na vida social e emocional do portador. Existem opções terapêuticas clínicas, mas a abordagem mais difundida é a cirúrgica com excisão das lesões, procedimento simples, com poucas complicações e menores taxas de recidivas locais. O objetivo deste estudo é descrever o tratamento cirúrgico do xantelasma palpebral, avaliar a satisfação dos pacientes no pós-operatório e as taxas de recidivas pós-cirúrgicas. Métodos: Trata-se de um estudo retrospectivo realizado com uma amostra de 25 pacientes submetidos a tratamento cirúrgico de xantelasmas palpebrais. O acompanhamento pós-operatório foi realizado em intervalos de 7 dias, 30 dias, 90 dias e 12 meses com entrevista, exame físico e aplicação de questionário que contemplaram identificação de recidivas locais, complicações pós-operatórias e satisfação com o resultado estético. Resultados: Quatro pacientes evoluíram com recidiva local e apenas dois pacientes manifestaram insatisfação com o resultado estético após o desfecho final. Em nenhum paciente submetido a ressecção cirúrgica das lesões associadas à autoenxertia foi observada recorrência ou insatisfação com o resultado estético. Conclusões: O tratamento cirúrgico como primeira opção na abordagem terapêutica dos xantelasmas palpebrais deve ser considerado, visto o impacto estético e psicológico de tal afecção. É uma técnica simples, de fácil aplicação e reprodutibilidade, eficaz, segura, com relevantes taxas de satisfação e baixa ocorrência de recidivas.

Introduction: Eyelid xanthelasma is the most common form of cutaneous xanthoma, characterized by yellowish patches on the eyelid's skin. Despite being a benign condition and not presenting with functional limitations, it is an important aesthetic complaint that impacts the patient's social and emotional life. There are clinical therapeutic options, but the most widespread approach is the surgical approach with excision of the lesions, a simple procedure with few complications and lower local recurrence rates. This study aims to describe the surgical treatment of palpebral xanthelasma, to assess postoperative patient satisfaction and post-surgical recurrence rates. Methods: This is a retrospective study with a sample of 25 patients undergoing surgical treatment of eyelid xanthelasmas. Postoperative follow-up was performed at intervals of 7 days, 30 days, 90 days and 12 months with an interview, physical examination and application of a questionnaire that included the identification of local recurrences, postoperative complications and satisfaction with the aesthetic result. Results: Four patients evolved with local recurrence, and only two expressed dissatisfaction with the aesthetic result after the outcome. No patient who underwent surgical resection of lesions associated with autograft recurrence or dissatisfaction with the aesthetic result was observed. Conclusions: Surgical treatment as the first option in the therapeutic approach of eyelid xanthelasmas should be considered, given the aesthetic and psychological impact of such a condition. It is a simple technique, easy to apply and reproducible, effective, and safe, with relevant satisfaction rates and low recurrences.

Inclisiran, ARN interferente pequeño: un nuevo enfoque para el tratamiento del colesterol / Inclisiran, small interfering RNA: a new approach to cholesterol treatment

Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.

Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

Alopecia Universal após Tratamento com Sinvastatina e Ezetimiba: Impactos na Família / Alopecia Universalis after Treatment with Simvastatin and Ezetimibe: Affects on Family

Resumo A alopecia areata (AA) é uma doença autoimune que se desenvolve no couro cabeludo ou em outras partes do corpo. A alopecia universal, que é uma forma rara de alopecia areata, é caracterizada pela perda de pelos que afeta todo o corpo. Nos dois pacientes apresentados, o tratamento com atorvastatina foi iniciado com o diagnóstico de hipercolesterolemia, mas, quando as metas de valores não foram alcançadas, foi iniciado o tratamento com uma combinação de sinvastatina e ezetimiba. Depois de um período de tratamento com sinvastatina e ezetimiba, o distúrbio de AA, o qual começou com a perda de cabelo no couro cabeludo, espalhou pelo corpo todo e se transformou em alopecia universal. Embora as estatinas possam causar alopecia com reações autoimunes, elas geralmente são utilizadas no tratamento da alopecia, por seus efeitos imunomoduladores.

Abstract Alopecia areata (AA) is an autoimmune disease that grows in the scalp or in other parts of the body. Alopecia universalis, which is a rare form of alopecia areata, is characterized by a loss of hair that affects the entire body. In the two patients presented in this study, atorvastatin treatment was implemented, with the diagnosis of hypercholesterolemia; however, when the target values were not reached, a combination of simvastatin and ezetimibe was implemented. After a period of simvastatin/ezetimibe treatment, the AA disorder, which began with hair loss on the scalp, spread to the entire body and turned into Alopecia Universalis. Although statins can cause alopecia with autoimmune reactions, they are generally used in the treatment of alopecia due to their immunomodulatory effects.

Hipertensión arterial asociada a osteoporosis en pacientes mujeres del hospital del Seguro Social, Trujillo

Objetivo: Determinar si la hipertensión arterial se encuentra asociada a osteoporosis en pacientes mujeres del Hospital I del Seguro Social en Trujillo. Materiales y métodos: El tipo de estudio realizado fue observacional, analítico y transversal. Participaron 351 pacientes mujeres atendidas en un consultorio del Servicio de Medicina Interna del Hospital I de Florencia de Mora de EsSalud en Trujillo durante el periodo 2016-2019. Según los criterios de selección, se dividieron en dos grupos: 175 pacientes con hipertensión arterial y 176 pacientes sin hipertensión arterial, para demostrar el número de pacientes con osteoporosis. Los datos se analizaron mediante la prueba chi cuadrado de Pearson con el paquete SPSS 26.0, para realizar el análisis estadístico, y así presentar los resultados obtenidos en gráficos y tablas, lo cual se realizó en Excel Windows 10. Resultados: Se encontró que la prevalencia de osteoporosis con hipertensión arterial fue del 31,4 %; la osteoporosis sin hipertensión arterial, 1,7 %. Esto evidencia que la prevalencia de osteoporosis en mujeres con hipertensión arterial es estadísticamente significativa (p < 0,001) respecto a las mujeres sin hipertensión arterial. En cuanto al análisis de las variables intervinientes, aquellas que fueron estadísticamente significativas fueron la edad (p < 0,001), el colesterol (p < 0,001) y el café (p < 0,001). Las variables como diabetes mellitus 2, sexo, obesidad, anemia, triglicéridos y tabaco no fueron estadísticamente significativas. Conclusiones: La hipertensión arterial sí se encuentra asociada a osteoporosis, así como las variables intervinientes como edad, colesterol y café, ya que fueron estadísticamente significativas.

Objective: To determine if hypertension is associated with osteoporosis in female patients of Seguro Social de Salud (EsSalud) Hospital I in Trujillo. Materials and methods: An observational, analytical and cross-sectional study, which included 351 female patients treated in the Internal Medicine Unit of EsSalud Hospital I Florencia de Mora, Trujillo, from 2016 to 2019. According to the screening criteria, patients were divided into two groups-175 with hypertension and 176 without hypertension-to determine the number of patients with osteoporosis. The data was analyzed with Pearson's chi-square test using IBM SPSS Statistics V26 to perform the statistical analysis and present the results in graphs and tables in Microsoft Excel Windows 10. Results: It was found that the prevalence of osteoporosis with hypertension accounted for 31.4 %, while that of osteoporosis without hypertension was 1.7 %. This shows that the prevalence of osteoporosis in women with hypertension is statistically significant (p < 0.001) with respect to women without hypertension. Regarding the analysis of the intervening variables, age (p < 0.001), cholesterol (p < 0.001) and coffee (p < 0.001) were statistically significant. Variables such as type 2 diabetes mellitus, sex, obesity, anemia, triglycerides and smoking were not statistically significant. Conclusions: Hypertension is associated with osteoporosis as well as with the intervening variables age, cholesterol and coffee, as they were statistically significant.

Relación de riesgo entre dislipidemia y COVID-19 / Risk relationship between dyslipemia and COVID-19

La presencia de dislipidemia en pacientes con la COVID-19 parece agravar el curso clínico de la enfermedad. En esta revisión bibliográfica se describen los principales mecanismos que las vinculan y sus implicaciones en el tratamiento de los pacientes afectados. Para realizar este trabajo se efectuó una búsqueda bibliográfica en bases de datos, tales como Google académico, SciELO, Annual Reviews y PMC. Los descriptores analizados fueron COVID-19, SARS-CoV-2, dislipidemia, LDL-colesterol, HDL-colesterol, triglicéridos, hipercolesterolemia y lipoproteínas VLDL. Se revisaron preferentemente artículos de revistas arbitradas por pares y disponibles a texto completo, publicados en inglés y español. A pesar de las controversias, la dislipidemia es un factor de riesgo de pronóstico desfavorable en afectados con la COVID-19 y el tratamiento para los pacientes con esa condición desfavorable mejora dicho pronóstico.

The presence of dyslipemia in patients with COVID-19 seems to increase the clinical course of the disease. In this literature review the main mechanisms that link them and their implications in the treatment of the affected patients are described. To carry out this work a literature search was made in databases, such as academic Google, SciELO, Annual Reviews and PMC. The analyzed describers were COVID-19, SARS-CoV-2, dyslipemia, LDL-cholesterol, HDL-cholesterol, triglycerides, hypercholesterolemia and VLDL lipoproteins. Articles of magazines arbitrated by pairs and available to complete text, published in English and Spanish were preferably revised. In spite of the controversies, dyslipemia is a risk factor of unfavorable prognosis in patients affected with COVID-19 and the treatment for the patients with that unfavourable condition improve this prognosis.

Criterios predictores en el diagnóstico de la hipercolesterolemia familiar / Predictive criteria in the diagnosis of familial hypercholesterolemia

Introducción: La hipercolesterolemia familiar es una enfermedad con alta prevalencia, no tratada acorta la esperanza de vida, por lo que el diagnóstico a edades tempranas resulta fundamental. Las pruebas genéticas constituyen el gold standard para el diagnóstico de hipercolesterolemia familiar, sin embargo, la no disponibilidad del test genético no debe constituir un impedimento para la adecuada conducta en estos casos. Objetivo: Identificar criterios clínicos predictores en el diagnóstico por pesquisa de la hipercolesterolemia familiar. Métodos: Se realizó un estudio descriptivo prospectivo a partir de una muestra de 393 pacientes (casos índices) de HF en el Hospital Clínico Quirúrgico Hermanos Ameijeiras; durante el período 2008-2018. Resultados: En la pesquisa familiar fueron identificados 177 (15,66 por ciento) nuevos casos de hipercolesterolemia familiar, de ellos se clasifican como casos positivos 35 (19,77 por ciento), casos probables 58 (32,77 por ciento) y casos posibles 84 (47,46 por ciento). Las categorías del estrato Make early diagnosis to prevent early death MEDPED y la edad del caso índice resultaron ser las variables clínicas de interés con mayor probabilidad para identificar nuevos casos de hipercolesterolemia familiar. Conclusiones: los criterios clínicos estandarizados de la escala make early diagnosis to prevent early death P y la edad del caso índice resultaron ser indicadores predictivos de gran valor para identificar y estratificar casos con variantes fenotípicas de hipercolesterolemia familiar(AU)

Introduction: Familial hypercholesterolemia is a disease with high prevalence; it shortens life expectancy if it is not treated, so early diagnosis is essential. Genetic tests are the gold standard for the diagnosis of familial hypercholesterolemia, however, the unavailability of the genetic test should not be an obstacle to proper conduct in these cases. Objective: To identify predictive clinical criteria in the diagnosis by screening of familial hypercholesterolemia. Methods: A prospective descriptive study was carried out from a sample of 393 patients (index cases) of FH at Hermanos Ameijeiras Surgical Clinical Hospital from 2008 to 2018. Results: In the family investigation, 177 (15.66 percent) new cases of familial hypercholesterolemia were identified, 35 of them (19.77 percent) are classified as positive cases, 58 (32.77 percent) as probable cases and 84 as possible cases (47.46 percent)The stratum categories of Make Early Diagnosis to Prevent Early Death (MEDPED) and the age of the index case turned out to be the clinical variables of interest with the greatest probability to identify new cases of familial hypercholesterolemia. Conclusions: The standardized clinical criteria of the make early diagnosis to prevent early death P scale and the age of the index case turned out to be highly valuable predictive indicators to identify and stratify cases with phenotypic variants of familial hypercholesterolemia(AU)

Hipercolesterolemia familiar descripción de un caso en una familia de Armenia - Quindío (Colombia)

Introducción: La Hipercolesterolemia familiar (HF) es una enfermedad genética de carácter autosómico dominante, poco frecuente, generada por la mutación en el cromosoma 19. Es la primera causa de enfermedad cardiovascular prematura. Las mutaciones patogénicas que generan la HF se relacionan con el receptor de LDL (LDLr), la apolipoproteina B-100 (Apo- B100) y la proteína convertasa subtilisina / kexina tipo 9 (PCSK9), que produce elevación del colesterol y alteración de la vía del LDLr en el 80 % de los casos diagnosticados de HF (5). Presentamos un reporte de caso de cuatro pacientes que pertenecen a la misma familia, quienes presentan mutaciones patogénicas de diferente compromiso a nivel cardiovascular y sistémico que ha afectado de manera negativa su cotidianidad. El objetivo de este trabajo es realizar una correlación del hipercolesterolemia familiar de tipo genético a partir de la literatura, con respecto a la serie de casos presentada, y evaluar el impacto que este genera en los servicios de salud, en la vida del paciente y su familia. Discusión: El reporte de caso que presentamos se fundamenta en la sospecha de HF según los criterios de Holanda. En estos pacientes se reconoce mutación del gen LDLr que se relaciona con HF. Sin embargo, no ha sido ampliamente estudiada. Chmara realizó en Polonia por primera vez un estudio en el que reportó la variante ac 11G>T. En Colombia, el estudio de López encontró tres mutaciones, identificadas como variante a c.11G > A, n c.416A > G y c.1187G > A (8). Conclusión: La HF en nuestro medio es poco frecuente y con gran impacto social, en la mayoría de los casos genera síntomas clínicos y aumento del riesgo cardiovascular desde una edad temprana. Es importante resaltar el diagnóstico oportuno y el conocimiento por parte del personal de salud para generar una calidad de vida adecuada a los pacientes y evitar que aumente el riesgo cardiovascular.

Introduction: Familial hypercholesterolemia (FH) is a rare autosomal dominant genetic disease caused by a chromosome 19 mutation. It is the main cause of premature cardiovascular disease. Pathogenic mutations which cause FH are related to the LDL receptor (LDLr), B-100 apolipoprotein (Apo-B100) and type 9 subtilisin/kexin convertase protein (PCSK9), causing blood cholesterol increase and impairment of the LDLr pathway in up to 80% of patients diagnosed with FH. We present the case of 4 patients belonging to the same family and who present pathogenic mutations leading to diverse kinds of cardiovascular and systemic disease. Discussion: The case report we are presenting is based on the suspicion of FH according to the dutch criteria. These patients had the LDLr gene mutation related to FH. However, this mutation has not been thoroughly studied. The ac 11G>T variant was reported for the first time in Poland by Chmara. In Colombia, Lopez found 3 mutations identified as variant a c.11G > A, variant n c.416A > G and variant c.1187G > A. Conclusion: FH is rare in Colombia. Early diagnosis and healthcare worker awareness must be highlighted to improve the quality of life and decrease the cardiovascular risk of patients.

Rastreamento para Hipercolesterolemia Familiar em Pequenos Municípios: A Experiência do Programa HipercolBrasil em 11 Municípios Brasileiros / Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Towns in the Hipercolbrasil Program

Resumo Fundamento A hipercolesterolemia familiar (HF) é uma doença genética dominante que se caracteriza por níveis sanguíneos elevados de colesterol de lipoproteína de baixa densidade (LDL-C), e está associada à ocorrência de doença cardiovascular precoce. No Brasil, o HipercolBrasil, que é atualmente o maior programa de rastreamento em cascata para HF, já identificou mais de 2.000 indivíduos com variantes genéticas causadoras de HF. A abordagem padrão baseia-se no rastreamento em cascata de casos índices referidos, indivíduos com hipercolesterolemia e suspeita clínica de HF. Objetivos Realizar rastreamento direcionado de 11 pequenos municípios brasileiros com suspeita de alta prevalência de indivíduos com HF. Métodos A seleção dos municípios ocorreu de 3 maneiras: 1) municípios em que houve suspeita de efeito fundador (4 municípios); 2) municípios em uma região com altas taxas de infarto do miocárdio precoce, conforme descrito pelo banco de dados do Sistema Único de Saúde (2 municípios); e 3) municípios geograficamente próximos a outros municípios com alta prevalência de indivíduos com HF (5 municípios). A significância estatística foi considerada como valor p < 0,05. Resultados Foram incluídos 105 casos índices e 409 familiares de primeiro grau. O rendimento dessa abordagem foi de 4,67 familiares por caso índice, o qual é significativamente melhor (p < 0,0001) do que a taxa geral do HipercolBrasil (1,59). Identificamos 36 CIs com variante patogênica ou provavelmente patogênica para HF e 240 familiares de primeiro grau afetados. Conclusão: Nossos dados sugerem que, uma vez detectadas, regiões geográficas específicas justificam uma abordagem direcionada para a identificação de aglomerações de indivíduos com HF.

Abstract Background Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated serum levels of low-density lipoprotein cholesterol (LDL-C), and it is associated with the occurrence of early cardiovascular disease. In Brazil, HipercolBrasil, which is currently the largest FH cascade screening program, has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach is based on cascade screening of referred index cases, individuals with hypercholesterolemia and clinical suspicion of FH. Objectives To perform targeted screening of 11 small Brazilian cities with a suspected high prevalence of people with FH. Methods The selection of cities occurred in 3 ways: 1) cities in which a founder effect was suspected (4 cities); 2) cities in a region with high rates of early myocardial infarction as described by the National Health System database (2 cities); and 3) cities that are geographically close to other cities with a high prevalence of individuals with FH (5 cities). Statistical significance was considered as p value < 0.05. Results One hundred and five index cases and 409 first-degree relatives were enrolled. The yield of such approach of 4.67 relatives per index case was significantly better (p < 0.0001) than the general HipercolBrasil rate (1.59). We identified 36 IC with a pathogenic or likely pathogenic variant for FH and 240 affected first-degree relatives. Conclusion Our data suggest that, once detected, specific geographical regions warrant a target approach for identification of clusters of individuals with FH.

Xantomas tuberosos en un paciente pediátrico: la clave en el diagnóstico precoz de una patología grave y poco frecuente / Tuberous xanthomas in a pediatric patient: a clue to the early diagnosis of a severe and infrequent disease

Los xantomas cutáneos reflejan el depósito de lípidos en la piel y pueden ser la única manifestación temprana de dislipidemias de inicio en la infancia. Las características y distribución de los xantomas orientan a la patología de base; los xantomas tuberosos tienen una fuerte asociación con la hipercolesterolemia homocigota familiar, una patología muy infrecuente. Su detección temprana otorga una ventana terapéutica para prevenir la ateroesclerosis acelerada y la mortalidad. Se presenta el caso de una paciente que comenzó a los dos años con xantomas tuberosos, que fueron la clave diagnóstica para identificar la hipercolesterolemia homocigota familiar subyacente.

Cutaneous xanthomas reflect lipid deposition on the skin and may be the only early manifestation of a childhoodonset dyslipidemia. Characteristics and distribution of the xanthomas signalize the underlying pathology, tuberousxanthomas being strongly associated with homozygous familial hypercholesterolaemia, an extremely rare condition. Its early detection provides a therapeutic window to prevent accelerated atherosclerosis and mortality. We present the case of a patient who started at two years with tuberous xanthomas, which were the diagnostic clue to identify the underlying homozygous familial hypercholesterolaemia.

Prevalência e fatores associados ao diagnóstico autorreferido de colesterol alto na população adulta brasileira: Pesquisa Nacional de Saúde 2019 / Prevalencia y factores asociados con el diagnóstico autoinformado de colesterol alto en la población adulta brasileña: Investigación Nacional de Salud 2019 / Prevalence and factors associated with self-reported diagnosis of high cholesterol in the Brazilian adult population: National Health Survey 2019

Objetivo: Estimar a prevalência de diagnóstico autorreferido de colesterol alto e analisar os fatores associados à prevalência na população adulta brasileira. Métodos: Estudo transversal utilizando a Pesquisa Nacional de Saúde 2019. O diagnóstico de colesterol alto foi autorreferido. Modelos de regressão de Poisson originaram as razões de prevalência (RP) e intervalos de confiança de 95% (IC95%). Resultados: Nos 88.531 adultos, a prevalência de colesterol alto foi de 14,6%. Associaram-se positivamente: sexo feminino (RP = 1,44; IC95% 1,40;1,52), idade ≥ 60 anos (RP = 3,80; IC95% 3,06;4,71), ter plano de saúde (RP = 1,33; IC95% 1,24;1,42), autoavaliação de saúde ruim ou muito ruim (RP = 1,75; IC95% 1,60;1,90), ter hipertensão (RP = 1,78; IC95% 1,68;1,89), ter diabetes (RP = 1,54; IC95% 1,45;1,65), ter insuficiência renal (RP = 1,33; IC95% 1,15;1,53), ter obesidade (RP = 1,27; IC95% 1,18;1,36), ser ex-fumante (RP = 1,13; IC95% 1,07;1,20), consumir álcool abusivamente (RP = 1,11; IC95% 1,01;1,21), ser ativo no lazer (RP = 1,22; IC95% 1,15;1,30). Conclusão: O colesterol alto associou-se a condições sociodemográficas, de saúde e estilo de vida.

Objetivo: Estimar la prevalencia de colesterol alto autodeclarado y analizar factores asociados la prevalencia en adultos brasileños. Métodos: Estudio transversal utilizando la Encuesta Nacional de Salud de 2019. El diagnóstico de colesterol alto fue autodeclarado. Los modelos de regresión de Poisson produjeron razón de prevalencia (RP) e intervalos de confianza del 95% (IC95%). Resultados: En 88.531 adultos, la prevalencia fue 14,6%. Asociaron positivamente: sexo feminino (RP = 1,44; IC95% 1,40;1,52), edad ≥ 60 años (RP = 3,80; IC95% 3,06;4,71), seguro salud (RP = 1,33; IC95% 1,24;1,42), autoevaluación de salud mala o muy mala (RP = 1,75; IC95% 1,60;1,90), hipertensión (RP = 1,78; IC95% 1,68;1,89), diabetes (RP = 1,54; IC95% 1,45;1,65), insuficiencia renal (RP = 1,33; IC95% 1,15;1,53), obesidad (RP = 1,27; IC95% 1,18;1,36), exfumador (RP = 1,13; IC95% 1,07;1,20), abuso de alcohol (RP = 1,11; IC95% 1,01;1,21), estar activo en el tiempo libre (RP = 1,22; IC95% 1,15;1,30). Conclusión: Colesterol alto se asoció con condiciones sociodemográficas, de salud y estilo de vida.

Objective: To estimate the prevalence of self-reported high cholesterol diagnosis and to analyze the factors associated with the prevalence in the Brazilian adult population. Methods: Cross-sectional study, using data from the 2019 National Health Survey. The diagnosis of high cholesterol was self-reported. Poisson regression models yielded prevalence ratios (PR) and 95% confidence intervals (95%CI). Results: In the 88,531 adults, the prevalence of high cholesterol was 14.6%. Positively associated: female sex (PR = 1.44; 95%CI 1.40;1.52), age ≥ 60 years (PR = 3.80; 95%CI 3.06;4.71), health insurance (PR = 1.33; 95%CI 1.24;1.42), poor or very poor self-rated health (PR = 1.75; 95%CI 1.60;1.90), hypertension (PR = 1.78; 95%CI 1.68;-1.89), diabetes (RP = 1.54; 95%CI 1.45;1.65), renal failure (PR = 1.33; 95%CI 1.15;1.53), obesity (PR = 1.27; 95%CI 1.18;1.36), former smoker (PR = 1.13; 95%CI 1.07;1.20), alcohol abuse (PR = 1.11; 95%CI 1.01;1.21), physically active during leisure time (PR = 1.22; 95%CI 1.15;1.30). Conclusion: High cholesterol was associated with sociodemographic characteristics, health condition and lifestyle.

Avaliação do perfil de microRNAs exossomais em portadores de hipercolesterolemia familial / Evaluation of the profile of exosomal microRNAs in patients with familial hypercholesterolemia

A Hipercolesterolemia Familial (HF) é uma doença hereditária do metabolismo lipídico que causa aos portadores alta incidência de aterosclerose prematura. A HF pode ser diagnosticada clínica e geneticamente, entretanto, apenas cerca de 40% podem ter confirmados pelo diagnostico molecular. Assim, outros sistemas de diagnóstico devem ser avaliados. Ultimamente devido a estabilidade em fluidos biológicos, os exossomos circulantes apresentam grande potencial, pois carreiam um número variado de compostos e são considerados veículos de intercomunicação entre os tecidos. Sabe-se que vários RNAs são carreados nos exossomos, incluindo miRNAs, lncRNA e uma variedade de proteínas. Estes componentes podem ser marcadores de diagnóstico para várias doenças inclusive a HF e suas complicações cardiovasculares. Foram utilizadas amostras de exossomos plasmáticos provenientes de 54 pacientes HF sem uso de estatina por, no mínimo, seis semanas, e 38 indivíduos normolipidêmicos para sequenciamento de miRNAs e estudo da proteômica. Os exossomos foram isolados utilizando dois métodos precipitação química e cromatográfica de exclusão de tamanho e caraterizados utilizando: dispersão de luz dinâmica, Western blotting, rastreamento de nanopartículas (NanoSight), imunomarcação e microscopia eletrônica de transmissão. Os miRNAs e proteínas foram extraídos dos exossomos e analisados por sequenciamento de nova geração e espectrometria de massa, respectivamente. Os dados clínicos, biodemográficos e laboratoriais dos pacientes HF e controles indicaram diferenças significativas esperadas entre os grupos, indicando que foram selecionados adequadamente. A caracterização físico-química dos exossomos mostrou resultados com tamanho de ˜90nm e imunorreação positiva para tetraspaninas. O resultado do sequenciamento identificou acima 2000 miRNAs. Os miR-122- 5p e miR-21-5p apresentaram expressão aumentada no grupo HF (log2FC=1,79 e log2FC=1,27, respectivamente), e o miR-122-5p pós normalização em relação ao controle manteve significativo comparados ao controle (p=0,034). A análise comparativa entre exossomos e plasma total mostrou diferença significativa, pois foram identificadas 239 proteínas (p <0,05) diferentes entre exossomos e plasma. Em exossomos, 17 proteínas foram aumentadas e 21 diminuídas em pacientes com HF em comparação com o controle (p <0,05). Destas, seis proteínas foram mais abundantes em HF e sete proteínas foram menos abundantes em exossomos de pacientes com HF em comparação com o controle. A análise de enriquecimento por bioinformática mostrou que a maior parte dessas moléculas (miRNAs e proteínas) foram relacionadas com metabolismo lipídico, dislipidemia, aterosclerose, doença arterial coronariana, adipogênese. Assim, na busca de novos alvos como potenciais biomarcadores de diagnóstico da HF, nossos resultados da análise integrativa entre os miRNAs e as proteínas exossomais abre novas frentes de pesquisa mais bem direcionadas, para a validação desses miRNAs e proteínas exossomais

Familial Hypercholesterolemia (FH) is an inherited disease of lipid metabolism that causes a high incidence of premature atherosclerosis in patients. FH can be diagnosed clinically and genetically, however, only about 40% can be confirmed by molecular diagnosis. Thus, other diagnostic systems should be evaluated. Lately, due to stability in biological fluids, circulating exosomes have great potential, as they carry a varied number of compounds and are considered vehicles of intercommunication between tissues. Several RNAs are known to be carried on exosomes, including miRNAs, lncRNA, and a variety of proteins. These components can be diagnostic markers for several diseases including FH and its cardiovascular complications. Plasma exosome samples from 54 FH patients without statin use for at least six weeks and 38 normolipidemic individuals were used for miRNA sequencing and proteomics studies. Exosomes were isolated using two methods chemical precipitation and size exclusion chromatography and characterized using: dynamic light scattering, Western blotting, nanoparticle tracking (NanoSight), immunostaining and transmission electron microscopy. MiRNAs and proteins were extracted from exosomes and analyzed by next-generation sequencing and mass spectrometry, respectively. Clinical, biodemographic and laboratory data of FH patients and controls indicated significant expected differences between the groups, indicating that they were appropriately selected. The physicochemical characterization of exosomes showed results with a size of ˜90nm and positive immunoreaction for tetraspanins. The sequencing result identified above 2000 miRNAs. miR-122-5p and miR-21-5p showed increased expression in the FH group (log2FC=1.79 and log2FC=1.27, respectively), and miR122-5p after normalization in relation to the control remained significant compared to the control (p=0.034). The comparative analysis between exosomes and total plasma showed a significant difference, as 239 different proteins (p < 0.05) were identified between exosome and plasma. In exosomes, 17 proteins were increased and 21 decreased in FH patients compared to control (p < 0.05). Of these, six proteins were more abundant in FH and seven proteins were less abundant in exosomes from patients with FH compared to the control. Bioinformatics enrichment analysis showed that most of these molecules (miRNAs and proteins) were related to lipid metabolism, dyslipidemia, atherosclerosis, coronary artery disease, adipogenesis. Thus, in the search for new targets as potential diagnostic biomarkers of FH, our results of the integrative analysis between miRNAs and exosomal proteins opens new and better-directed research fronts for the validation of these miRNAs and exosomal proteins

Avaliação do perfil de metilação dos genes LDLR, PCSK9, LDLRAP1 em pacientes portadores de hipercolesterolemia familial / Evaluation of the methylation profile of LDLR, PCSK9, LDLRAP1 genes in patients with familial hypercholesterolemia

As variabilidades genotípicas que determinam algumas alterações fenotípicas e metabólicas podem ter seu diagnostico falho se baseado apenas nos dados genômicos. Na hipercolesterolemia familial (HF) pode-se observar que os dados de variantes nos genes da LDLR, PCSK9, APOB e LDLRAP1 sugeridos pelos consensos atuais para confirmar o diagnóstico, tem mostrado serem insuficientes, mostrando baixa porcentagem de confirmação, mesmo nos dos casos em que características fenotípicas apresentam dados sugestivos importantes. A complementação no auxílio diagnóstico com dados epigenéticos tem sido sugerida em muitas doenças, principalmente nas crônicos degenerativos. A metilação do DNA pode estar envolvida no mecanismo que regulam vários processos metabólicos, entre os quais os envolvidos na expressão de proteínas e neste estudo os que estão envolvidos no metabolismo do colesterol, que poderia explicar fenótipos hipercolesterolemicos sem demonstração clara de variantes nos genes de consenso. O objetivo do presente estudo foi comparar o perfil de metilação dos genes LDLR, PCSK9 e LDLRAP1 entre pacientes com diagnóstico de Hipercolesterolemia Familial confirmado através de variantes genéticas descritas na literatura e pacientes sem diagnóstico confirmado. Além da comparação com indíviduos normolipidêmicos. A seleção dos indivíduos foi realizada na Seção de Dislipidemia do Instituto Dante Pazzanese de Cardiologia (IDPC), do Departamento de Análises Clínicas e Toxicológicas da Universidade Federal do Rio Grande do Norte (UFRN), da Universidade Estadual de Campinas (UNICAMP) e da Faculdade de Medicina de São José do Rio Preto (FAMERP). Através dos critérios MEDPED foram selecionados 133 pacientes para a realização do sequenciamento de um painel de genes relacionados ao fenótipo de HF e a homeostasia do colesterol a fim de confirmar o diagnóstico. Todos os pacientes tiveram o DNA purificado, que foi submetido ao tratamento com bissulfito, amplificado, purificado, desnaturado e sequenciado no sistema PyroMark Q24. Avaliou-se o perfil de metilação, em sítio CpG dos genes da LDLR, PCSK9 e LDLR AP1. A análise estatística foi realizada utilizando o software SPSS v.19, GraphPad Prism, versão 1.03 e o e o software R. 4.1.0. Os pacientes foram classificados em Grupo I: Pacientes com diagnóstico molecular confirmado pelo estudo fenotípico e genotipico (n=40); Grupo II: Pacientes fenotipicamente determinados como hipercolesterolemico, mas sem diagnóstico molecular confirmado pelo estudo genomico (n=93); Grupo III: indivíduos fenotipicamente determinados normolipidêmicos de acordo com a V Diretriz Brasileira de Dislipidemia (n=23). A análise comparativa entre os grupos I x II e II x III, demonstrou diferença estatísta significativa em 13 sítios CpG do total de 28 sítios CpG analisados nos três genes. Além disso, foi possível concluir que alterações nos sítios CpG presentes no gene LDLR influenciaram na presença de xantomas e arco córneo. Houve correlação positiva entre a idade e perfil de metilação do gene PCSK9, assim como, alterações nos sítios CpG deste gene influenciaram na presença de arco córneo e IAM. Além disso, alterações no sítio CPG presente no gene LDLRAP1 influenciou no desenvolvimento de DAC, IAM e RM, além da presença de xantelasma

The genotypic variabilities that determine some phenotypic and metabolic alterations can be misdiagnosed if based only on genomic data. In familial hypercholesterolemia (FH) it can be observed that the data of variants in the genes of LDLR, PCSK9, APOB and LDLR AP1 suggested by the current consensus to confirm the diagnosis, has shown to be insufficient, showing a low percentage of confirmation, even in the cases in which phenotypic characteristics present important suggestive data. Complementing the diagnostic aid with epigenetic data has been suggested in many diseases, especially in chronic degenerative diseases. DNA methylation may be involved in the mechanisms that regulate several metabolic processes, including those involved in the expression of proteins that ,in this study, are involved in cholesterol metabolism, which could explain hypercholesterolemic phenotypes without a clear demonstration of variants in consensus genes. The aim of the present study was to compare the methylation profile of LDLR, PCSK9 and LDLRAP1 genes between patients with a diagnosis of Familial Hypercholesterolemia confirmed through genetic variants described in the literature and patients without a confirmed diagnosis. In addition to the comparison with normolipidemic individuals. The selection of individuals was carried out at the Dyslipidemia Section of the Instituto Dante Pazzanese de Cardiologia (IDPC), in the Department of Clinical and Toxicological Analyzes of the Federal University of Rio Grande do Norte (UFRN), in the State University of Campinas (UNICAMP) and in the Faculdade of Medicine of São José do Rio Preto (FAMERP). Through the MEDPED criteria, 133 patients were selected to perform the sequencing of a panel of genes related to the FH phenotype and cholesterol homeostasis in order to confirm the diagnosis. All patients had their DNA purified, which were subjected to bisulfite treatment, amplified, purified, denatured and sequenced on the PyroMark Q24 system. The methylation profile in the CpG site of the LDLR, PCSK9 and LDLRAP1 genes were evaluated. Statistical analysis were performed using SPSS v.19 software, GraphPad Prism, version 1.03 and R. 4.1.0 software. Patients were classified into Group I: Patients with a molecular diagnosis confirmed by phenotypic and genotypic studies (n=40); Group II: Patients phenotypically determined to be hypercholesterolemic, but without a molecular diagnosis confirmed by the genomic study (n=93); Group III: phenotypically determined normolipidemic individuals according to the V Brazilian Dyslipidemia Directive (n=23). The comparative analysis between groups I x II and II x III showed a statistically significant difference in 13 CpG sites of the total of 28 CpG sites analyzed in the three genes of the project. Furthermore, it was possible to conclude that alterations in the CpG sites present in the LDLR gene influenced the presence of xanthomas and arc corneum. There was a positive correlation between age and PCSK9 gene methylation profile, as well as changes in the CpG sites of this gene influenced the presence of arc corneum and AMI. In addition, alterations in the site present in the LDLRAP1 gene are influencing the development of CAD, AMI and MR, in addition to the presence of xanthelasma

Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS - Brasil / Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Efecto de la inhibición de la proteína símil angiopoyetina tipo 3 (ANGPTL3): utilidad para el tratamiento de las dislipemias graves / Angiopoietin-like type 3 (angptl) inhibition: its role in the treatment of severe dyslipidemia

Las variantes de ANGPTL3 con pérdida de función están asociadas con efectos beneficiosos sobre el metabolismo lipídico y de carbohidratos y con riesgo reducido de enfermedad coronaria. Los cambios beneficiosos en los parámetros lipídicos que se obtienen con la inhibición de ANGPTL3 junto con la reducción en aterosclerosis que se observa en modelos animales y en estudios epidemiológicos de genética humana hacen de ANGPTL3 un nuevo objetivo terapéutico para prevenir las enfermedades cardiovasculares. Dos estrategias novedosas han surgido para inhibir esta proteína: un anticuerpo monoclonal y un oligonucleótido antisentido, con capacidad para reducir tanto el colesterol como los triglicéridos plasmáticos en forma notoria. Aunque el horizonte es promisorio, todavía no sabemos si los efectos de una variante presente desde el comienzo de la vida serán reproducidos por la inhibición de esta proteína que se realiza más tarde en la vida a través de una intervención farmacológica. (AU)

Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease. The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epi-demiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention. (AU)

Glycoinsulinemic parameters associated with vitamin D status in patients with chronic kidney disease undergoing dialysis therapy

ABSTRACT Evidence indicates that the physiological role of vitamin D goes beyond regulating classical domains of minerals and hormones. It is reported that the low status of Vitamin D may contribute to the occurrence of metabolic disorders, with emphasis on insulin resistance, atherosclerotic events and metabolic syndrome. In this sense, this study aimed to verify the association between metabolic and anthropometric parameters and vitamin D status in patients with chronic kidney disease undergoing hemodialysis. This was a cross-sectional study conducted with 95 patients with chronic kidney disease treated at clinics in Teresina, Piaui, Brazil. Lipid and inflammatory profile, glycemia, insulin and vitamin D status were determined. Data were analyzed using STATA software, adopting significance level of p<0.05. The results pointed to a significant association between vitamin D concentrations and adiposity of patients. It was observed that the high blood glucose and HOMA-IR values presented statistical association with vitamin D concentrations, and conditioned greater chances of their inadequacy. There was no correlation between nutrient concentrations and cytokines evaluated in the study. Therefore, it was concluded that the increase in levels of glycoinsulinemic parameters (insulin and HOMA-IR) seems to influence vitamin D status in patients with chronic kidney disease.

RESUMEN La evidencia indica que el papel fisiológico de la vitamina D va más allá de regular los dominios clásicos del eje mineral y hormonal. Hay trabajos que muestran que el bajo nivel de vitamina D puede contribuir a la aparición de trastornos metabólicos, con énfasis en la resistencia a la insulina, eventos ateroscleróticos y síndrome metabólico. En este sentido, el objetivo de este estudio fue verificar la asociación entre parámetros metabólicos y antropométricos y el estado de vitamina D en pacientes renales crónicos en hemodiálisis. Se trata de un estudio transversal realizado con 95 pacientes con enfermedad renal crónica atendidos en consultas externas de Teresina, Piauí, Brasil. Se determinó el perfil lipídico e inflamatorio, la glicemia, la insulina y el estado de vitamina D. Los datos se analizaron utilizando programa STATA , con un nivel de significancia de p<0,05. Los resultados apuntaron a una asociación significativa entre las concentraciones de vitamina D y la adiposidad de los pacientes. Se observó que los valores elevados de glucosa en sangre y HOMA-IR se asociaron estadísticamente con las concentraciones de vitamina D y condicionaron mayores posibilidades de su insuficiencia. No hubo correlación entre las concentraciones de nutrientes y las citocinas evaluadas en el estudio. Por tanto, se concluyó que el aumento de los niveles de parámetros glucoinsulinémicos (insulina y HOMA-IR) parece influir en el estado de la vitamina D en pacientes con enfermedad renal crónica.