Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real / Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis

Resumo Fundamento: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. Objetivos: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. Métodos: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. Resultados: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. Conclusões: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Abstract Background: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. Objectives: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. Methods: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Results: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Conclusions: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

Impacto de la optimización del tratamiento hipolipemiante en el riesgo cardiovascular residual / Impact of Optimizing Lipid-Lowering Therapy on Residual Cardiovascular Risk

RESUMEN Introducción: el modelo SMART-REACH predice el riesgo de eventos cardiovasculares recurrentes. Objetivos: los objetivos de este estudio fueron: a) evaluar el riesgo residual en una población en prevención secundaria y niveles de colesterol asociado a lipoproteínas de baja densidad (C-LDL) fuera de meta; b) mediante un modelo de simulación, determinar el impacto de optimizar las terapias hipolipemiantes en términos de reducción del riesgo residual. Material y métodos: estudio transversal, descriptivo y multicéntrico. Se incluyeron consecutivamente pacientes con antecedentes cardiovasculares y un C-LDL mayor o igual que 55 mg/dL. El riesgo de eventos recurrentes (infarto agudo de miocardio, accidente cerebrovascular o muerte vascular) a 10 años y a lo largo de la vida se estimó utilizando el modelo SMART-REACH. Mediante una simulación, se optimizó el tratamiento hipolipemiante de cada paciente (utilizando estatinas, ezetimibe o inhibidores de proproteína convertasa subtilisina kexina tipo 9 [iPCSK9]), se estimó el descenso del C-LDL, se verificó el alcance del objetivo lipídico y se calculó la reducción del riesgo cardiovascular y el número necesario a tratar (NNT) correspondiente. Resultados: se incluyeron 187 pacientes (edad media 67,9 ± 9,3 años, 72,7% hombres). Los riesgos residuales calculados a 10 años y a lo largo de la vida fueron 37,1 ± 14,7% y 60,3 ± 10,7%, respectivamente. Globalmente, se pudo optimizar una sola estrategia farmacológica con estatinas, ezetimibe o un iPCSK9 en el 38,5%, el 11,5% y el 5,5% de la población, respectivamente. La optimización basada en dos tratamientos se realizó en el 27,5% (estatinas + ezetimibe), el 7,7% (estatinas + iPCSK9) y el 1,1% (ezetimibe + iPCSK9) de los casos. En 15 pacientes se optimizó el tratamiento considerando los tres fármacos. El 53,9% y el 62,9% de las acciones para optimizar el tratamiento mostraron un NNT menor que 30 para evitar un evento a 10 años o a lo largo de la vida, respectivamente. Conclusión: en este estudio, los pacientes con antecedentes cardiovasculares que no alcanzan la meta de C-LDL mostraron un riesgo residual considerable. La simulación mostró un importante margen para optimizar el tratamiento, con un impacto notable en el riesgo residual.

ABSTRACT Background: The SMART-REACH model predicts the risk or recurrent cardiovascular events. Objectives: The objectives of this study were: a) to evaluate the residual cardiovascular risk in a secondary prevention population with LDL-C levels above the recommended goal, using a simulation model; and b) to determine the impact of optimizing lipid-lowering therapies in terms of residual cardiovascular risk reduction. Methods: We conducted a cross-sectional, descriptive and multicenter study. Patient with a history of cardiovascular disease and a LDL-C ≥55 mg/dL were consecutively included. The 10-year and lifetime risk of recurrent events (myocardial infarction, stroke, or vascular death) were estimated using the SMART-REACH model. By means of a simulation, lipid-lowering treatment was optimized for each patient [using statins, ezetimibe and/or PCSK9 (PCSK9) inhibitors], with estimation of LDL-C reduction, checking if lipid-lowering goal was achieved and calculating the reduction in cardiovascular risk and the corresponding number needed to treat (NNT). Results: The cohort was made up of 187 patients; mean age was 67.9 ± 9.3 years and 72.7% were men. The calculated 10-year and lifetime residual risks were 37.1 ± 14.7% and 60.3 ± 10.7%, respectively. Overall, treatment was optimized with a single pharmacological strategy with statins, ezetimibe or PCSK9 inhibitor in 38.5%, 11.5% and 5.5% of the population, respectively. Optimization based on two treatments was performed in 27.5% (statins + ezetimibe), 7.7% (statins + PCSK9 inhibitor) and 1.1% (ezetimibe + PCSK9 inhibitor) of the cases. In 15 patients, treatment was optimized when the three drugs (statins + ezetimibe + PCSK9 inhibitor) were considered. Overall, 53.9% and 62.9% of the actions implemented to optimize treatment showed a 10-year or lifetime NNT < 30 to prevent an event, respectively. Conclusion: In this study, patients with a history of cardiovascular disease who do not reach LDL-C goal showed significant residual cardiovascular risk. The simulation model showed a significant margin for optimizing treatment, with a marked reduction in residual cardiovascular risk.

Real World Evidence of Bempedoic Acid on Efficacy and Safety in Patients with Uncontrolled LDL-c and at High Risk of CVD

Background and Objective: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality worldwide, with high-risk patients requiring effective management to reduce their risk of cardiovascular events. Bempedoic acid is a novel therapeutic agent recently approved as an add-on therapy to statins in patients with uncontrolled LDL-c. Bempedoic acid inhibits cholesterol synthesis in the liver, which ultimately reduces the risk of cardiovascular events. Therefore, the present study aims to assess the efficacy and safety of bempedoic acid in patients with uncontrolled LDL-c (Previously on moderate or high-intensity statins) with a high risk of CVD in real-world settings. Methods: This is a multicenter, retrospective, observational study on the data of high-risk-CVD patients collected from Bempedoic Acid on Efficacy and Safety in patients (BEST) Registry. The clinical data of 140 patients who were already on statin therapy and were receiving Bempedoic acid at a dose of 180 mg, along with measurements of the level of LDL-c, HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, serum creatinine was taken into consideration. The primary outcome includes a change in LDL-c level, and secondary outcomes involve a change in the level of HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, and serum creatinine at week 12 and 24. Adverse events were reported at both time points. Results: A total of 140 patients were included in the present study with a mean age of 51.8 ± 9.2 years and had primary confirmed diagnosis of dyslipidemia with uncontrolled LDL-c. The mean levels of LDL-c decreased from the mean baseline value of 142.67 ± 46.49 mg/dL, to 106.78 ±33.92 mg/d; a statistically significant reduction by 23.23% (p < 0.01) at week 12. Similarly, at week 24, the mean LDL-c value reduced to 90.39 ± 38.89 mg/dL. A 33.38 % decrease was observed (p < 0.01). Other parameters such as non-HDL, FPG, PPPG, AST and serum creatinine also showed statistically significant reduction at week 12 and week 24. Conclusion: The present study demonstrates that bempedoic acid is an effective add-on medication in lowering LDL-c levels in high-risk CVD patients with uncontrolled LDL-c.

Acompanhamento de Dois Anos de Pacientes com Cardiopatia Isquêmica Crônica em um Centro Especializado no Brasil / Two-Year Follow-Up of Chronic Ischemic Heart Disease Patients in a Specialized Center in Brazil

Resumo Fundamento A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Objetivos Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Métodos Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. Resultados De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 - 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. Conclusão O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.

Abstract Background The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. Objectives This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. Results From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. Conclusion This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.

Clinical characteristics and follow-up status of patients aged 75 years and above undergoing coronary stenting and the rate of achieving low-density lipoprotein cholesterol / 西安交通大学学报(医学版)

【Objective】 To investigate the clinical characteristics, long-term follow-up rate, level and control rate of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) aged ≥75 years who underwent percutaneous coronary intervention (PCI) during hospitalization. 【Methods】 We selected ASCVD patients aged ≥75 years with PCI from January 2016 to December 2020 in The First Affiliated Hospital of Xi’an Jiaotong University, collected the baseline data of the patients and the follow-up of 1 month, 3 months, 6 months and 12 months after discharge by HIS system, and analyzed their LDL-C and control rate at each follow-up. 【Results】 A total of 1 129 patients were enrolled in this study, aged 78 (ranging from 75 to 89) years. Among them 72.1% were male; myocardial infarction was the main type of ASCVD (71.5% ); hypertension was the most common risk factor, accounting for 85.2% (717/842), followed by diabetes, 58.6% (493/842); 74.6% met the ultra-high risk criteria of the 2020 Chinese Expert Consensus on Lipid Management in Ultra-High Risk ASCVD Patients, and the LDL-C control rate was only 8.1% . The four routine follow-up rates of 1 129 elderly ASCVD patients were 49.5%, 24.1%, 17.1%, and 24.6%, respectively. The detection rates of LDL-C during follow-up were 26.3%, 5.3%, 10.4%, and 13.8%, respectively. LDL-C control rates in ultra-high risk ASCVD were 59.4%, 45.1%, 37.1%, and 17.6%, respectively, while LDL-C control rates in non-ultra-high risk ASCVD patients were 67.3%, 55.6%, 47.4%, and 44.0%, respectively. 【Conclusion】 The elderly patients with ASCVD-PCI were mainly ultra-high risk patients. The routine follow-up rate and the LDL-C compliance rate during follow-up were low and showed a downward trend.

A Case Report of Homozygous Familial Hypercholesterolemia Liver Transplantation / 罕见病研究

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.

Tratamiento posterior a un ataque cerebrovascular con estatinas y metas de colesterol de baja densidad / Statin treatment and low density cholesterol targets in patients post stroke

RESUMEN INTRODUCCIÓN: El ACV es uno de los eventos cardiovasculares más prevalentes en el mundo, en Colombia es la segunda causa de muerte y la primera de discapacidad. Uno de los factores de riesgo más importantes para tener en cuenta es el control del colesterol, la reducción de los niveles de C-LDL, principalmente por medio del tratamiento con estatinas y otros fármacos hipolipemiantes. MATERIALES Y MÉTODOS: En esta revisión narrativa de la literatura se ha recogido la información más relevante sobre el uso y los beneficios de este tratamiento y algunas consideraciones adicionales. CONCLUSIÓN: Los hallazgos de esta revisión demuestran el efecto protector de esta terapia cuando se consiguen reducir los niveles de C-LDL y colesterol, además, las otras terapias como ezetimiba o inhibidores de PSCK9. Por otro lado, los estudios mencionan posibles efectos beneficiosos en el contexto de ACV pero se requieren más ensayos clínicos.

ABSTRACT INTRODUCTION: Stroke is one of the most prevalent cardiovascular events in the world, in Colombia it is the second cause of death and first in disability. One of the most important risk factors to consider is cholesterol control, the reduction of LDL-C and cholesterol levels, mainly through treatment with statins and other lipid-lowering drugs. MATERIALS AND METHODS: The most relevant information on the use and benefits of this treatment and some additional considerations have been collected in this narrative review of the literature. CONCLUSION: The results of this narrative review show the protective effect of this therapy when it is possible to reduce LDL-C and cholesterol levels, in addition to other therapies such as ezetimibe or PSCK9 inhibitors. On the other hand, studies mention possible beneficial effects in the context of stroke but more clinical trials are required.

Comparação das Novas Equações de Martin/Hopkins e Sampson para o Cálculo do Colesterol de Lipoproteína de Baixa Densidade em Pacientes Diabéticos / Comparison of Novel Martin/Hopkins and Sampson Equations for Calculation of Low-Density Lipoprotein Cholesterol in Diabetic Patients

Resumo Fundamentos A determinação precisa do colesterol de lipoproteína de baixa densidade (LDL-C) é importante para se alcançar concentrações de LDL-C recomendadas por diretrizes e para reduzir resultados cardiovasculares adversos em pacientes diabéticos. A equação de Friedewald comumente usada (LDL-Cf) produz resultados imprecisos em pacientes diabéticos devido a dislipidemia diabética associada. Recentemente, duas novas equações - Martin/Hopkins (LDL-CMH) e Sampson (LDL-Cs) - foram desenvolvidas para melhorar a precisão da estimativa de LDL-C, mas os dados são insuficientes para sugerir a superioridade de uma equação sobre a outra. Objetivos O presente estudo comparou a precisão e a utilidade clínica das novas equações de Martin/Hopkins e Sampson em pacientes diabéticos. Método Foram incluídos no estudo quatrocentos e dois (402) pacientes com diabetes. O risco cardiovascular dos pacientes e as metas de LDL-C foram calculadas por diretrizes europeias. As concentrações de LDL-Cmh, LDL-Cs, e LDL-Cf calculadas foram comparadas à concentração de LDL-C direto (LDL-Cd) para testar a concordância entre essas equações e LDL-Cd. Um P valor <0,05 foi aceito como estatisticamente significativo. Resultados A LDL-CMH e a LDL-Cs tiveram concordância melhor com o LDL-Cd em comparação com a LDL-Cf, mas não houve diferenças estatísticas entre as novas equações para concordância com o LDL-Cd (Alfa de Cronbach de 0,955 para ambos, p=1). Da mesma forma, a LDL-CMH e a LDL-Cs tinham um grau semelhante de concordância com o LDL-Cd para determinar se o paciente estava dentro da meta de LDL-C (96,3% para LDL-Cmh e 96,0% para LDL-Cs), que eram ligeiramente melhores que a LDL-Cf (94,6%). Em pacientes com uma concentração de triglicérides >400 mg/dl, a concordância com o LDL-Cd foi ruim, independentemente do método usado. Conclusão As equações de Martin/Hopkins e Sampson mostram uma precisão similar para o cálculo de concentrações de LDL-C nos pacientes com diabetes, e ambas as equações são ligeiramente melhores que a equação de Friedewald.

Abstract Background The accurate determination of low-density lipoprotein cholesterol (LDL-C) is important to reach guideline-recommended LDL-C concentrations and to reduce adverse cardiovascular outcomes in diabetic patients. The commonly used Friedewald equation (LDL-Cf), gives inaccurate results in diabetic patients due to accompanying diabetic dyslipidemia. Recently two new equations - Martin/Hopkins (LDL-Cmh) and Sampson (LDL-Cs) - were developed to improve the accuracy of LDL-C estimation, but data are insufficient to suggest the superiority of one equation over the other one. Objective The present study compared the accuracy and clinical usefulness of novel Martin/Hopkins and Sampson equations in diabetic patients. Methods This study included 402 patients with diabetes. Patients' cardiovascular risk and LDL-C targets were calculated per European guidelines. Calculated LDL-Cmh, LDL-Cs, and LDL-Cf concentrations were compared with direct LDL-C concentration (LDL-Cd) to test agreement between these equations and LDL-Cd. A p-value <0.05 was accepted as statistically significant. Results Both LDL-Cmh and LDL-Cs had a better agreement with LDL-Cd as compared to LDL-Cf, but no statistical differences were found among novel equations for agreement with LDL-Cd (Cronbach's alpha 0.955 for both, p=1). Likewise, LDL-Cmh and LDL-Cs showed a similar degree of agreement with LDL-Cd in determining whether a patient was in a guideline-recommended LDL-C target (96.3% for LDL-Cmh and 96.0% for LDL-Cs), which were marginally better than LDL-Cf (94.6%). In patients with a triglyceride concentration >400 mg/dl, agreement with LDL-Cd was poor, regardless of the method used. Conclusion Martin/Hopkins and Sampson's equations show a similar accuracy for calculating LDL-C concentrations in patients with diabetes, and both equations were marginally better than the Friedewald equation.

Blood lipid and hematoma enlargement and outcome in patients with intracerebral hemorrhage / 国际脑血管病杂志

Early hematoma enlargement is one of the main factors of early neurological deterioration in patients with intracerebral hemorrhage. The correlation between blood lipid and hematoma enlargement is a research hotspot at present. This article reviews the relationship between blood lipid and hematoma enlargement and outcomes in patients with intracerebral hemorrhage, as well as the correlation between statin treatment and hematoma enlargement.

Reason of postprandial low-density lipoprotein cholesterol reduction measured by enzymatic assays: based on nuclear magnetic resonance method / 中华检验医学杂志

Objective:To explore the postprandial plasma low-density lipoprotein cholesterol (LDL-C) changes by various detection methods.Methods:A total of 85 subjects admitted to the Second Xiangya Hospital of Central South University from November 2017 to May 2019 were included. Serum samples were collected from fasting and the 2 nd hour and the 4 th hour after breakfast. Serum lipid levels were measured with enzymatic assays and nuclear magnetic resonance spectroscopy (NMRS), and proprotein invertase subtilisin/kexin type 9 (PCSK9) levels were measured with enzyme-linked immunosorbent assays. The differences of blood lipid components at different time points were compared by Friedman two-way rank analysis of variance and Wilcoxon signed rank test, and the correlation between PCSK9 level and lipoprotein particles was analyzed by Spearman correlation. Results:Measured by enzymatic assays, compared with the fasting state, LDL-C decreased at the 2 nd hour and the 4 th hour after the meal (2.58[2.09, 3.12], 2.47[1.92, 3.02], 2.37[1.82, 2.80] mmol/L, P<0.001). Measured by NMRS, the concentration of LDL particles (1 086[830, 1 239], 1 083[848, 1 213], 1 061[814, 1 213] nmol/L, P=0.417) did not change significantly, and cholesterol in LDL particles were 2.13 (1.56, 2.54), 2.16 (1.68, 2.50), 2.06 (1.58, 2.50) mmol/L, respectively ( P=0.047)，and postprandial cholesterol in LDL particles in the 2 nd hour and in the 4 th hour did not change significantly compared with fasting ( P>0.05). while the concentration of large LDL particles (185.2[150.6,221.6], 173.0[144.8,220.3], 178.1[144.0,233.6] nmol/L, P=0.001), and the cholesterol level in large LDL particles (0.49[0.39, 0.57], 0.47[0.38, 0.57], 0.46[0.37, 0.58]mmol/L, P<0.001) decreased after the meal. The PCSK9 level also decreased significantly after the meal (299[233, 397], 257[208, 342], 251[215, 340] ng/ml, P<0.001). There was an independent positive correlation between the decrease of PCSK9 levels and the increase of remnant cholesterol detected by MNRS after the meal ( r=0.232, P=0.035). Conclusions:The postprandial LDL-C level measured by NMRS and enzymatic assays is not consistent. The decrease of LDL-C measured by enzymatic assays is not caused by the clearance of LDL particles, but by the redistribution of cholesterol in each LDL subfraction.

Lower LDL-cholesterol levels associated with increased inflammatory burden in patients with acute ST-segment elevation myocardial infarction

SUMMARY OBJECTIVE: Association of low-density lipoprotein cholesterol and highly sensitive C-reactive protein in ST-elevation myocardial infarction patients was assessed in this study. METHODS: 591 consecutive patients who were hospitalized with a diagnosis of ST-elevation myocardial infarction were enrolled and assigned into tertiles according to their serum low-density lipoprotein cholesterol levels. Differences in highly sensitive C-reactive protein among low-density lipoprotein cholesterol tertiles and correlations between highly sensitive C-reactive protein and low-density lipoprotein cholesterol were assessed. RESULTS: Highly sensitive C-reactive protein levels differed significantly among the groups (p<0.001) and found to be highest in the low-density lipoprotein cholesterol tertile 1 and lowest in the low-density lipoprotein cholesterol tertile 3 (post-hoc p-values: tertile 1 vs. 2 <0.001; tertile 1 vs. 3 <0.001; tertile 2 vs. 3=0.019). There was a negative correlation between hs-CRP and both low-density lipoprotein cholesterol (r=-0.332, p<0.001) and total cholesterol (r=-0.326, p<0.001). There was also a negative correlation between highly sensitive C-reactive protein and high-density lipoprotein cholesterol, though the strength of this relationship was weak (r=-0.103, p=0.014). CONCLUSION: Lower low-density lipoprotein cholesterol levels are associated with higher inflammatory burden in patients with acute STEMI. Further studies are required to elucidate the significance of low-density lipoprotein cholesterol levels in ST-elevation myocardial infarction settings.

Índice de Masa Corporal una medida antropométrica asociada a Índice TG/HDL, un novel factor de riesgo cardio-metabólico / Body Mass Index An Anthropometric Measure Associated With TG / HDL Index, A Novel Cardio-Metabolic Risk Factor

Objetivos: determinar la relación entre obesidad e índice TG/HDL en pacientes atendidos en el servicio de consulta externa de endocrinología del hospital nacional Sergio Bernales en el año 2018. Métodos: el estudio fue observacional, analítico, tipo casos y controles no emparejado a razón de 4:1, con un total 288 sujetos de estudio siendo 230 controles y 58 casos quienes cumplieron con criterios de selección, involucro a los pacientes atendidos en el servicio de consulta externa endocrinología. La muestra fue aleatoria simple, se incluyeron las variables, Sexo, edad, Índice de masa corporal, Colesterol total, Triglicéridos total, HDL-c, LDL-c, Índice TG/HDL. Se empleó un modelo de regresión logística para obtener un Odds Ratio para fuerza de asociación. Resultados: La frecuencia relativa de obesidad fue del 65.52% y 29.13%, para los casos y controles respectivamente, a su vez una significancia estadística con la prueba exacta de Fisher, P-valor 0.000. Se encontró un por regresión logística bivariada una relación entre Obesidad e Índice TG/HDL-c (OR 4.62, p=0.000, IC95% 2.51-8.52). Conclusiones: se encontró una relación entre la Obesidad y el índice TG/HDL-c pudiéndose extrapolar a población adulta atendida en el servicio de endocrinología de Lima Metropolitana, este es el primer artículo publicado al respecto a nivel nacional, se recomiendan estudios prospectivos para determinar causalidad.

Objectives: to determine the relationship between obesity and the TG / HDL index in patients treated at the endocrinology outpatient service of the Sergio Bernales national hospital in 2018. Methods: the study was observational, analytical, case-control type not matched to ratio of 4: 1, with a total of 288 study subjects, 230 controls and 58 cases who met the selection criteria, involved the patients treated in the endocrinology outpatient service. The sample was simple random, the variables were included: Sex, age, Body mass index, Total cholesterol, Total triglycerides, HDL-c, LDL-c, TG / HDL index. A logistic regression model was used to obtain an Odds Ratio for the strength of association. Results: The relative frequency of obesity was 65.52% and 29.13%, for cases and controls respectively, in turn a statistical significance with Fisher's exact test, P-value 0.000. A bivariate logistic regression found a relationship between Obesity and TG / HDL-c Index (OR 4.62, p = 0.000, 95% CI 2.51-8.52). Conclusions: a relationship was found between Obesity and the TG / HDL-c index, which can be extrapolated to the adult population treated in the endocrinology service of Metropolitan Lima, this is the first article published in this regard at the national level, prospective studies are recommended to determine causality.

Aplicación sistemática de un algoritmo para el manejo lipídico en pacientes de muy alto riesgo cardiovascular. Impacto en los objetivos lipídicos / Systematic Application of an Algorithm for Lipid Management in Cardiovascular High-Risk Patients. Impact on Lipid Goals

RESUMEN Objetivo: Analizar el tratamiento hipolipemiante indicado y verificar el cumplimiento de las metas lipídicas recomendadas durante la internación y en el seguimiento precoz, luego de aplicar sistemáticamente un algoritmo para el manejo lipídico basado en las recomendaciones actuales. Material y métodos: Se incluyeron en forma consecutiva pacientes internados con síndrome coronario agudo o revascularización programada. Se aplicó sistemáticamente un algoritmo para el manejo lipídico, que incluyó: 1) indicación precoz de estatinas de alta intensidad en la internación; 2) seguimiento precoz (controles a las 6 y 12 semanas). La terapia indicada se basó en los documentos de posición de la Sociedad Argentina de Cardiología. Se analizó el cumplimiento de las metas de C-LDL (<70 mg/dl) a las 6 y 12 semanas. Resultados: Se incluyeron 292 pacientes. Se indicó estatinas (95,9% de alta intensidad) a todos los pacientes al alta hospitalaria. A las 6 semanas, el 62,5% alcanzó la meta de C-LDL. Se modificó el esquema terapéutico en el 36,3% de los sujetos (aumento de la dosis de estatinas: 19,7%; agregado de ezetimibe: 67,7%). A las 12 semanas, el 69,1% del subgrupo que no había alcanzado la meta a las 6 semanas logró el objetivo lipídico. Se indicó un inhibidor de la PCSK9 (iPCSK9) a 7 pacientes. Globalmente, el 88,4% alcanzó la meta de C-LDL a las 12 semanas. Conclusión: La aplicación sistemática de un algoritmo basado en las guías determinó que muchos sujetos de alto riesgo cardiovascular alcanzaran las metas de C-LDL a las 12 semanas. La indicación de un iPCSK9 quedó reservada para un grupo reducido de pacientes.

ABSTRACT Objective: The aim of this study was to analyze the indicated lipid-lowering therapy and verify the achievement of the recommended lipid goals during hospitalization and early follow-up, after the systematic application of a lipid management algorithm based on current recommendations. Methods: Patients hospitalized for acute coronary syndrome or programmed revascularization surgery were prospectively included in the study. A lipid management algorithm, including; 1) early indication of high-intensity statins during hospitalization and 2) early follow-up (6 and 12-week controls), was systematically applied. The therapy indicated was based on position documents of the Argentine Society of Cardiology. Achievement of LDL-C goals (<70 mg/dl) at 6 and 12 weeks was analyzed. Results: A total of 292 patients were prescribed statins (high-intensity in 95.9% of cases) at hospital discharge. AT 6 weeks, 62.5% reached the LDL-C goal. The therapeutic plan was modified in 36.3% of patients (increased dose of statins in 19.7% and addition of ezetimibe in 67.7%). At 12 weeks, 69.1% of the subgroup which has not fulfilled the goal at 6 weeks, attained the lipid target. A PCSK9 inhibitor (PCSK9i) was indicated in 7 patients. Overall, 88.4% of patients achieved the LDL-C goal at 12 weeks. Conclusion: Many cardiovascular high-risk patients reached LDL-C goals at 12 weeks with the systematic application of a guideline-based algorithm. The indication of a PCSK9i was reserved for a reduced group of patients.

Metas lipídicas en pacientes diabéticos. Implicaciones clínicas luego de aplicar una nueva fórmula para el cálculo del colesterol-LDL / Lipid Goals in Diabetic Patients. Clinical Implications after Application of a New Formula for LDL-cholesterol Calculation

RESUMEN Introducción: Existen claras recomendaciones para el manejo lipídico en los diabéticos. Una nueva fórmula para el cálculo del C-LDL mejoraría la imprecisión de la fórmula de Friedewald. Objetivos: Analizar el uso de estatinas y el cumplimiento de las metas lipídicas en pacientes diabéticos, evaluando las consecuencias de aplicar una nueva fórmula para el cálculo del C-LDL. Métodos: Estudio descriptivo, transversal y multicéntrico. Se incluyeron diabéticos tipo 2 mayores de 18 años. El C-LDL se calculó con la fórmula clásica (Friedewald) y la nueva fórmula. Se siguieron las recomendaciones del documento de posición para el uso adecuado de estatinas (Sociedad Argentina de Cardiología). Resultados: Se incluyeron 528 pacientes. En prevención secundaria, el 77,2% recibió estatinas (23,4% alta intensidad). El 36,6% y el 36,0% alcanzaron la meta de C-LDL menor a 70 mg/dL y de C-noHDL inferior a 100 mg/dL, respectivamente. El 20,8% de los pacientes con un C-LDL menor de 70 mg/dL (Friedewald) salió de meta al aplicar la nueva fórmula. En los pacientes en prevención primaria con factores de riesgo o daño de órgano blanco, el 62,2% recibió estatinas (14,7% alta intensidad). El 20,9% y el 20,4% alcanzaron la meta de C-LDL menor a 70 mg/dL y de C-noHDL inferior a 100 mg/dL. El 27,7% de los pacientes con un C-LDL menor de 70 mg/dL (Friedewald) salió de meta al aplicar la nueva fórmula. A mayor nivel de triglicéridos, más pacientes salieron de meta de C-LDL con la nueva fórmula. Conclusión: El cumplimiento de las metas lipídicas y el uso adecuado de estatinas en esta población fue deficiente. Aplicar la nueva fórmula de C-LDL optimizó la evaluación de estos pacientes.

ABSTRACT Background: There are clear recommendations for lipid management in diabetic patients. A new formula for the calculation of LDL-cholesterol (LDL-C) would improve the inaccuracy of the Friedewald formula. Objectives: The aim of this study was to analyze the use of statins and the fulfillment of lipid goals in diabetic patients, evaluating the consequences of applying a new formula for LDL-C calculation. Methods: This was a descriptive, cross-sectional, multicenter study including type 2 diabetic patients over 18 years of age. LDL-C was calculated using the classic Friedewald formula and the new formula. Recommendations of the position document for the appropriate use of statins from the Argentine Society of Cardiology were followed. Results: A total of 528 patients were included in the study. In secondary prevention, 77.2% of patients received statins (23.4% high-intensity statins) and 36.6% and 36.0% of these patients achieved the goals of LDL-C below 70% mg/dl and non-HDL-C below 100 mg/dl, respectively. In 20.8% of patients with LDL-C below 70 mg/dl according to the Friedewald formula, this goal was not attained when the new formula was applied. In primary prevention, 62.2% patients with risk factors or white organ damage received statins (14.7% high-intensity statins) and 20.9% and 20.4% achieved the goals of LDL-C below 70% mg/dl and non-HDL-C below 100 mg/dl. In 27.7% of patients with LDL-C below 70 mg/dl using the Friedewald formula, this goal was not reached when applying the new formula. More patients did not achieve the LDL-C goal with the new formula when the triglyceride level was higher. Conclusion: In this population, the appropriate use of statins and the fulfillment of lipid goals were poor. Applying the new LDL-C formula optimized the evaluation of these patients.

Effect of Functional Feed Catfish (Clarias gariepinus) Oil and Probiotic Enterococcus faecium IS-27526 on Lipid Profile of Aged Atherogenic Female Cynomolgus Monkey (Macaca fascicularis)

@#Introduction: Catfish oil contains saturated and unsaturated fatty acids. Polyunsaturated fatty acid contributes to maintain the lipid profile. Enterococcus faecium IS-27526 is a novel indigenous probiotic of dadih origin. The aim of this study was to find out the effect of probiotic and catfish (Clarias gariepinus) based functional feed on lipid profile of aged female Cynomolgus monkey/CM (Macaca fascicularis) fed with atherogenic diet. Methods: Nine CMs were randomly devided into 3 groups, in single blind intervention study for 90 days , namely: A1= atherogenic diet as control positive, A2= probiotic, A3= probiotic + catfish oil after 45 days adaptation period. The average of CM’s bodyweight was in a range of 3 to 4 kg. The main ingredients of atherogenic diet were catfish flour, egg, sugar, egg yolk flour, and condiments. Serum lipid profile was assessed monthly by Cholesterol Oxidase-Peroxidase Aminoantipyrine (CHOP-POD) methods for cholesterol, LDL and HDL, while Glycerol-3-Phosphate Oxidase Peroxidase-Antiperoxidase (GPO-PAP) method for Triglyceride. Results: Atherogenic diet did not significantly affect appetite and bodyweight of the animals (p=0,12). The atherogenic diet significantly increased cholesterol and LDL level of animals (p=0.03 and p = 0.04) after 90 days administration . The CMs fed with probiotic E. faecium IS-27526 and catfish oil showed significant higher serum cholesterol (p=0,03) and LDL levels (p=0,04) compared to atherogenic diet alone and atherogic diet with probiotic E. faecium IS-27526. Probiotic E. faecium IS-27526 at 108 cfu/day stabilized the cholesterol and LDL level after 90 days administration compared with other groups of intervention. The TG and HDL of each group showed within normal range during the whole intervention study. Conclusion: Atherogenic feed significantly increased cholesterol and LDL level of CMs. Probiotic E. faecium IS-27526 showed a potential beneficial effect in maintaining lipid profile and could prevent dyslipidemia.

PCSK9 Inhibitors: Clinical Relevance, Molecular Mechanisms, and Safety in Clinical Practice / Inibidores de PCSK9: Importância Clínica, Mecanismos Moleculares, e Segurança na Prática Clínica

Abstract Coronary artery disease (CAD) is one of the leading causes of mortality. High circulating levels of low-density lipoprotein (LDL) in the blood are associated with cardiovascular mortality, whether through an etiological role or through its association with the progression of CAD per se. Randomized clinical trials have shown that, when LDL levels are reduced, cardiovascular risk is also reduced, which reinforces this association. The first major trial involving a hypolipidemic agent of the statin family, the Scandinavian Simvastatin Survival Study (4S), was published in 1994 and found a significant reduction in mortality in patients at high cardiovascular risk. However, even in subsequent studies with different statins, a residual risk persisted, and this seems not to have changed over time; it is speculated that this risk may be due to statin intolerance. In this scenario, the potential exists for novel hypolipidemic agents to drive a true revolution in the therapy of dyslipidemia. The recent discovery of PCSK9 inhibitors (PCSK9i), a class of hypolipidemic monoclonal antibodies, is extremely promising. PCSK9 inhibition is capable of promoting a mean LDL reduction of up to 60%, with potential for very significant clinical repercussions, as every 38 mg/dL reduction in LDL appears to be associated with a 22% reduction in cardiovascular risk. This review addresses a brief history of PCSK9i, major trials of these drugs, cardiovascular outcomes, and aspects related to their efficacy and safety. Finally, the molecular mechanisms and possible pleiotropic effects of PCSK9i are also discussed.

Resumo A doença arterial coronariana (DAC) é uma das principais causas de mortalidade. Níveis circulantes elevados de lipoproteína de baixa densidade (LDL) no sangue estão associados com mortalidade cardiovascular, seja por um papel etiológico ou por sua associação com a progressão da DAC em si. Estudos clínicos randomizados mostram que, quando os níveis de LDL são reduzidos, o risco cardiovascular também é reduzido, o que reforça tal associação. O primeiro ensaio importante envolvendo um agente hipolipemiante da família da estatina, o estudo Scandinavian Simvastatin Survival Study (4S), foi publicado em 1994 e encontrou uma redução significativa na mortalidade de pacientes com risco cardiovascular elevado. Contudo, mesmo em estudos subsequentes com diferentes estatinas, observou-se um risco residual persistente, o qual aparentemente não mudou ao longo dos anos. Especula-se que esse risco se deve à intolerância às estatinas. Nesse cenário, existe um potencial para novos agentes hipolipemiantes que levem a uma verdadeira revolução no tratamento das dislipidemias. A descoberta recente dos inibidores de PCSK9 (PCSK9i), uma classe de anticorpos monoclonais, é extremamente promissora. A inibição da PCSK9 é capaz de promover uma redução média nos níveis de LDL de até 60%, com potencial para repercussões clínicas muito significativas, já que para cada redução de 38 mg/dL, parece haver uma redução de 22% no risco cardiovascular. Esta revisão aborda uma breve história dos PCSK9i, os principais ensaios envolvendo esses medicamentos, desfechos cardiovasculares, e aspectos relacionados a sua eficácia e segurança. Finalmente, os mecanismos moleculares e possíveis efeitos pleiotrópicos dos PCSK9i são também discutidos.

Evaluation of Collagen Fibers, MMP2, MMP9, 8-OHdG and Apoptosis in the Aorta of Ovariectomized LDL Knockout Mice Submitted to Aerobic Exercise / Avaliação de Fibras de Colágeno, MMP2, MMP9, 8-OH-Dg e Apoptose na Aorta de Ratas LDL Nocaute Ovariectomizadas Submetidas a Exercício Aeróbico

Abstract Background: In menopause, there is greater cellular exposure to oxidative stress, related to the decreased antioxidative effects of estrogen. These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. The 8-OHdG is one of the main markers of DNA oxidative damage induced by reactive oxygen species (ROS). Objective: We aimed to investigate effects of moderate aerobic training on the ascending aorta of LDL-knockout (LDL-KO) and ovariectomized female mice. Methods: A total of 15 C57BL/6 mice and 15 LDL-KO mice were divided into experimental groups. The thickness and volume density of types I and III collagen fibers were performed by morphoquantitative analysis, whereas the MMP-2 and MMP-9 and 8-OHdG were detected by immunohistochemistry and apoptosis was detected by the TUNEL assay. The significance level for all tests was p < 0.05. Results: Exercise causes an increase in the thickness of the aorta in LDL-KO groups, particularly accentuated in the ovariectomized groups. The type I collagen fibers showed an increase in volume density influenced by training in both Control groups and in the LDL-KO group. Type III collagen density decreased in both groups. The MMP-2 showed moderade immunostaining in the tunica media in LDL-KO groups, which did not occur in the control groups and the MMP-9 stained irregularly in all tissues. The marker 8-OhdG was stronger in the exercise training groups. Additionally, the ovariectomy, the exercise training and the LDL-KO treatments increased apoptosis. Conclusion: These results suggest that moderate-intensity aerobic exercise in ovariectomized mice associated to an increase in LDL rate possibly increases oxidative stress and apoptosis induction.

Resumo Fundamento: Na menopausa, há maior exposição celular ao estresse oxidativo, relacionada à diminuição dos efeitos antioxidantes do estrogênio. Essas alterações metabólicas favorecem a progressão das doenças cardiovasculares, como a aterosclerose. A função anormal da aorta - a artéria mais importante - está associada a muitas doenças cardiovasculares. O colágeno, especialmente os tipos I e III, é um dos mais importantes componentes da parede da aorta e pode ser afetado por muitos fatores, incluindo a menopausa. Por sua vez, 8-OHdG é um dos principais marcadores de danos oxidativos do DNA induzidos por espécies reativas de oxigênio (EROS). Objetivo: Investigar os efeitos do treinamento aeróbico moderado na aorta ascendente de camundongos fêmeas, nocaute para LDL (LDL-KO) e ovariectomizadas. Métodos: Um total de 15 animais C57BL/6 e 15 animais LDL-KO foram divididos em grupos experimentais. A espessura e a densidade de volume das fibras de colágeno tipos I e III foram realizadas por análise morfoquantitativa; MMP-2 e MMP-9 e 8-OHdG foram detectadas por imunohistoquímica; e a apoptose foi detectada pelo ensaio TUNEL. O nível de significância adotado para todos os testes realizados foi p < 0,05. Resultados: o exercício causa aumento da espessura da aorta em grupos LDL-KO, particularmente acentuada em grupos ovariectomizados. As fibras de colágeno de tipo I mostraram aumento da densidade de volume influenciado pelo treinamento em animais controle e LDL-KO. A densidade do colágeno tipo III diminuiu em ambos os grupos. A MMP-2 mostrou imunomarcação moderada na túnica média em animais LDL-KO; em grupos controle, a MMP-9 marcou irregularmente em todos os tecidos. O marcador 8-OHdG foi mais forte nos grupos de treinamento de exercícios. Além disso, a ovariectomia, o treinamento físico e os tratamentos de LDL-KO aumentaram a apoptose. Conclusão: Esses resultados sugerem que exercícios aeróbicos de intensidade moderada em camundongos ovariectomizados associados ao aumento da taxa de LDL, possivelmente, aumentam o estresse oxidativo e a indução da apoptose.