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Objective@#To investigate the prevalence of major chronic diseases among residents in Xiamen City, Fujian Province, so as to provide insights into enhancing the prevention and control of chronic diseases.@*Methods@#The residents aged 18 years and older and lived for 6 months and more were selected from 6 districts in Xiamen City from 2021 to 2022 using the stratified random sampling method. Demographic information, disease history, blood pressure, fasting blood glucose and blood cholesterol were collected through questionnaire surveys, physical examination and laboratory tests. The prevalence rates of hypertension, diabetes and hypercholesterolemia were calculated and standardized using the 2020 National Population Census data, and were analyzed by age and gender.@*Results@#Totally 22 289 residents were investigated, including 10 444 males (46.86%) and 11 845 females (53.14%). The prevalence rates of hypertension, diabetes and hypercholesterolemia were 15.35%, 4.30% and 10.45%, and the standardized prevalence rates were 16.25%, 4.81% and 10.21%, respectively. The standardized prevalence rates of hypertension, diabetes and hypercholesterolemia in males were 19.20%, 5.71% and 9.97%, respectively, and were higher than those in females, which were 13.62%, 4.03% and 10.29%, respectively (all P<0.05). The crude prevalence rates of hypertension and diabetes in males aged 18 to 59 years were higher than those in females, the crude prevalence rate of hypercholesterolemia in males aged 18 to 49 years was higher than that in females, and the crude prevalence rate of hypercholesterolemia aged 50 years and over in males was lower than that in females (all P<0.05).@*Conclusion@#From 2017 to 2022, the prevalence rates of hypertension, diabetes, and hypercholesterolemia in males were higher than those in females in Xiamen City, while the prevalence rate of hypercholesterolemia in females was higher than that in males after the age of 50 years.
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OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.
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O uso de plantas medicinais como forma de tratamento para várias doenças é uma tradição que se estende entre gerações, há milhares de anos. Os povos antigos costumavam usar partes específicas de alguns vegetais para a realização de chás e curativos para feridas. Ainda nos dias atuais, muitas pessoas preferem as formas naturais como tratamento para suas comorbidades, principalmente como adjuvantes no combate às dislipidemias. O presente trabalho teve o objetivo de analisar as plantas Cynara scolymus L e Artemisia absinthium L para confirmar a presença ou ausência de proteases específicas contra a hipercolesterolemia. A pesquisa foi realizada através de uma triagem das plantas no software RCSB (https://www.rcsb.org/). No final, pode-se confirmar que a planta Cynara scolymus L atende às perspectivas de tratamento da hipercolesterolemia, enquanto a Artemisia absinthium L não apresentou valores suficientes que sejam eficazes no tratamento.
The use of medicinal plants as a form of treatment for various diseases is a tradition that has spanned generations for thousands of years. Ancient people used to use specific parts of some vegetables to make teas and dressings for wounds. Even today, many people prefer natural forms as a treatment for their comorbidities, especially as adjuvants in the fight against dyslipidemia. The present work aimed to analyze the plants Cynara scolymus L and Artemisia absinthium L to confirm the presence or absence of specific proteases against hypercholesterolemia. The research was carried out by screening the plants using the RCSB software (https://www.rcsb.org/). In the end, it can be confirmed that the Cynara scolymus L plant meets the prospects for treating hypercholesterolemia, while Artemisia absinthium L did not present sufficient values that are effective in the treatment.
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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.
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Antecedentes: un alto porcentaje de pacientes con dislipemia no alcanza los objetivos terapéuticos de colesterol unido a lipoproteínas de baja densidad (C-LDL) en el nivel primario de atención. Objetivo: Describir el manejo terapéutico de la dislipemia en pacientes sin enfermedad cardiovascular aterosclerótica (ECA) establecida, desde la perspectiva del médico de atención primaria en España. Material y Métodos: Estudio transversal mediante encuesta electrónica dirigida a médicos de atención primaria para explorar su manejo terapéutico farmacológico de la dislipemia en pacientes sin ECA, que se centraba en su conocimiento y adherencia a las guías de la Sociedad Europea de Cardiología/Sociedad Europea de Aterosclerosis (ESC/AES) de 2019 y su perspectiva con respecto a las barreras para alcanzar los objetivos de C-LDL. Resultados: Un total de 279 médicos de atención primaria completaron la encuesta. La mayoría (80,65%) afirmaron que ya habían adoptado las guías de la ESC/EAS de 2019 en su práctica. Sin embargo, alrededor del 30% seguía los objetivos terapéuticos de las guías anteriores (2016) y muchos trataban a sus pacientes con estatinas en monoterapia y dosis menores a la máxima tolerada. Adicionalmente un 50,18% era poco adherente a las guías de la ESC/EAS de 2019, especialmente al algoritmo de tratamiento. Las barreras más importantes para alcanzar los objetivos de C-LDL eran la subestimación del riesgo cardiovascular y la reticencia a aumentar la dosis o a utilizar terapia combinada. Conclusiones: Aunque los médicos de atención primaria afirman que seguían las guías ESC/EAS de 2019, los resultados indican que no las habían integrado completamente en su práctica clínica.
Background: Evidence suggests many dyslipidemic patients do not reach target low-density lipoprotein and cholesterol (LDL-C) levels in primary health care. Objective: We aimed to describe the pharmacologic therapeutic management of dyslipidemia in patients without established atherosclerotic cardiovascular diseases (ASCVD) from the primary care physician's perspective in Spain. Material and Methods: We conducted a cross-sectional study through an online survey directed to primary care physicians to explore their therapeutic management of dyslipidemia in patients without ASCVD, focusing on their knowledge and adherence to the 2019 European Society of Cardiology/ European Atherosclerosis Society (ESC/EAS) guidelines and their perspective concerning the barriers to achieving LDL-C therapeutic targets. Results: In total, 279 primary care physicians completed the survey. Most interviewees (80.65%) stated they had already adopted the 2019 ESC/EAS guidelines in their clinical practice. Nevertheless, around 30% adhered to therapeutic targets by previous ESC/EAS guidelines (2016), and most treated their patients mainly with statins in monotherapy, prescribing doses below the maximum tolerated. Additionally, 50.18% were classified as low adherence to the 2019 ESC/EAS guidelines, especially to the treatment algorithm. According to the physicians, the underestimation of patients' cardiovascular risk and the reluctance to increase doses or use combined therapy were the most critical barriers to achieving LDL-C targets. Conclusions: Although primary care physicians in our survey reported adherence to the 2019 ESC/EAS guidelines recommendations, our observations indicate they need to integrate them better into their clinical practice.
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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.
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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.
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OBJECTIVE To explore the mechanism of Cirsium japonicum extract in improving hypercholesterolemia based on metabolomics technology. METHODS The extract of C. japonicum was prepared by macroporous resin adsorption， and its main components were identified by liquid chromatography-tandem mass spectrometry. The experimental mice were randomly divided into control group （n＝6） and modeling group （n＝16）. The hypercholesterolemia model was induced by diet in modeling group； after modeling， the rats of modeling group were divided into model group （n＝8） and C. japonicum extract group （n＝8）. C. japonicum extract group was given C. japonicum extract 400 mg/（kg·d） by gavage （calculated by extract）， and other 2 groups were given constant volume of 0.3% sodium carboxymethyl cellulose solution， for 6 weeks. After medication， the intervention effect of C. japonicum extract was evaluated by the levels of serum total cholesterol （TC）， triglyceride （TG） and the histopathological changes of liver. The mechanism of C. japonicum extract in improving hypercholesterolemia model mice was investigated by metabolomics. RESULTS It was identified that C. japonicum extract contained 12 components， such as 030302005） chlorogenic acid， linarin and pectolinarin. After 6 weeks of intervention， compared with control group， serum level of TC was increased significantly while the level of TG was decreased significantly in model group （P＜0.05）， while a large number of lipid droplets， disorderly arrangement of liver cells and the damaged structure of liver cord were observed in liver tissue. Compared with model group， the serum level of TC was decreased significantly in C. japonicum extract group（P＜0.05）； the lipid droplets in liver tissue were significantly reduced， with liver cells arranged radially and tightly centered around the central vein， and liver cords arranged neatly. The metabolomics study showed that after the intervention of C. japonicum extract， the levels of metabolites were significantly adjusted back， such as ethanolamine， fumaric acid and cholesterol； finally， three metabolism pathways， such as alanine-aspartate-glutamic acid metabolism， arginine biosynthesis， citric acid cycle， were obtained. CONCLUSIONS The main components of C. japonicum extract are phenolic acids and flavonoids， such as chlorogenic acid， linarin， pectolinarin. C. japonicum extract can improve hypercholesterolemia by regulating the contents and distribution of differential metabolites， adjusting alanine-aspartate-glutamic acid metabolism， arginine biosynthesis and citric acid cycle， participating in oxidation-reduction reaction， improving liver lipid accumulation， and playing anti-inflammatory role.
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Objective To evaluate the efficacy,safety and cost-effectiveness of alirocumab for the treatment of hypercholesterolemia in a rapid health technology assessment(rHTA).Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data and health technology assessment(HTA)relative websites were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literatures on the alirocumab for the treatment of hypercholesterolemia from inception to August 14th,2022.Two reviewers independently screened the literature,extracted the data results and accessed the quality of included studies.Descriptive analysis and summary were then performed.Results A total of 38 documents were included,including 28 systematic reviews/Meta analyses,7 pharmacoeconomic studies and 3 HTA reports.This study showed that,compared with placebo or other lipid lowering therapy,alirocumab lowered the levels of LDL-C,Lp(a),TC,TG,Apo B,non-HDL-C,increased the levels of HDL-C and Apo A1,reduced the risk of major adverse cardiovascular events(MACE),all-cause mortality,cerebrovascular events,and unstable angina,but did not reduce cardiovascular death,myocardial infarction or coronary revascularization.Safety studies showed that,compared with placebo or other lipid lowering therapy,alirocumab did not increase the risk of other adverse reactions but associated with higher injection site reactions.Pharmacoeconomic studies showed that alirocumab was cost-effective in patients with three branch coronary artery disease and acute coronary syndrome with LDL-C≥2.59 mmol·L-1.Conclusion Alirocumab is effective and safe for the treatment of hypercholesterolemia,and cost-effective for the patients of coronary arteriosclerotic heart disease with multi-vessel disease or with high base-line level of LDL-C.
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Homozygous familial hypercholesterolemia (HoFH) is a rare and serious autosomal genetic metabolic disease. Patients without intervention often die younger than 30 years old from early atherosclerotic cardiovascular disease (ASCVD)incurred by extremely high levels of low-density lipoprotein cholesterol (LDL-C). We present a case of HoFH, a child with compound heterozygous mutation in this study. The effect of conventional lipid-lowering therapy through diet control and lipid-lowering drugs was unsatisfactory. The blood-lipid purification proves effective but has poor compliance and difficult to maintain for a longer time. The patient received orthotopic liver transplantation and had been followed for 2 years, with the patient shows normal LDL-C, well growth and development. We hope the case will provide the clinician with better understanding of the diagnosis and treatment of the rare disease of HoFH.
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Familial hypercholesterolemia (FH) is a group of autosomal co-dominant genetic diseases mainly characterized by abnormal low-density lipoprotein related metabolism. It is one of the most common inherited diseases in children and one of the most serious lipid metabolism diseases which results in various life-threatening cardiovascular diseases and the complications. In recent years, the treatment protocols for FH have diversified thanks to the deeper understanding of the disease in China and abroad and the development of new lipid-lowering drugs. However, the current awareness and diagnosis rate of FH are very low. The treatment of the disease is much inadequate. This paper summarizes the clinical characteristics, diagnosis, screening strategy, and treatment of FH hoping to enhance the understanding and awareness of the disease in the society.
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Syphilis may affect the cardiovascular system, in which coronary arteries are less commonly involved. Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease with elevated low-density lipoprotein-cholesterol (LDL-C) levels due to impaired LDL-C clearance. We report a young male patient with syphilis and FH. The clinical manifestations were acute myocardial infarction and high LDL-C levels. Coronary angiography and intracoronary imaging showed multiple aneurysmal ectasia and stenosis. A drug-eluting stent was implemented when recurrent restenosis occurred after two percutaneous coronary drug-eluting balloon angioplasties.
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Familial hypercholesterolemia(FH)is an autosomal dominant disease.Homozygous FH patients tend to have a high incidence of severe arteriosclerotic cardiovascular disease during adolescence and die at ages of 20-30.Liver transplantation(LT)may correct the dysfunction of LDL receptor on hepatocytes, restore normal lipoprotein metabolism, arrest disease progression and improving patient outcomes.However, due to a great rarity of LT for FH, domestic transplantation centers lack the relevant clinical experiences.This review summarized some important issues of FH patients undergoing LT, such as indications, timing, donor sources, efficacies, complications and reusing diseased liver.The goal was to provide practical references for managing FH.
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@#Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disease characterized by increased concentrations of low-density lipoprotein (LDL-C) cholesterol in the blood. The risk of premature coronary heart disease in FH patients may increase without early treatment. Advancement in molecular biology techniques has enable early detection and diagnosis of FH. These techniques are cost-effective and have a shorter turnaround time. The current diagnostic tools available for FH diagnosis involving algorithm-based scoring criteria and various molecular diagnosis methods including next-generation sequencing (NGS), Sanger sequencing, Multiplex ligation-dependent probe amplification (MLPA) and DNA hybridisation assay are discussed in this review. However, molecular genetic testing is not widely available due to time-consuming procedures, high cost and requires trained personnel. Thus, this 36 review highlights the use of point of care (POC) testing as an approach to diagnose FH, particularly in countries lacking infrastructure and expertise in this field. Lateral flow testing (LFA) has gained attention as a POC diagnostic tool due to its simplicity, low cost and involved simple procedure and settings. The advantages of LFA made this technique a potential tool in addressing challenges in diagnosing FH, particularly for early diagnosis of family members.
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Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by abnormal lipoprotein metabolism. Patients with FH have a significantly increased risk of coronary artery disease (CAD) due to long-term exposure to high levels of low-density lipoprotein (LDL). The diagnosis of FH relies heavily on gene detection, and examination of LDL receptor (LDLR) function is of great significance in its treatment. This review summarizes the current advances in the screening, diagnosis, and treatment of FH and functional analysis of LDLR gene mutations.
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Humanos , Hiperlipoproteinemia Tipo II/terapia , Doença da Artéria Coronariana , Lipoproteínas LDL , MutaçãoRESUMO
Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC50 = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.
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Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.
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Abstract Lipoprotein monitoring is desirable in the management of medical conditions such as atherosclerotic cardiovascular disease and coronary artery disease, in which controlling the concentration of these chylomicrons is crucial. Current clinical methods are complex and present poor reproducibility between laboratories. For these reasons, recent guidelines discard the assessment of low-density lipoprotein cholesterol (LDL-C) as a routine analysis during lipid-lowering therapies. Concerning the importance of monitoring this parameter, the authors present an electrochemical immunosensor constructed from a simple and easy-to-reproduce platform that allows detecting and quantifying LDL nanoparticles directly from human serum samples. The performance of the biosensor was studied by scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The biosensing platform displays good stability and linearity between 30 mg dL-1 and 135 mg dL-1 with a detection limit of 20 mg dL-1. The proposed biosensor can be easily employed for monitoring LDL concentration in clinical treatments.
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Transição de Fase , Lipoproteínas LDL/análise , Microscopia Eletrônica de Varredura/métodos , Eletroquímica/instrumentação , Espectroscopia Dielétrica/métodos , Hipercolesterolemia/classificaçãoRESUMO
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.
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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.