A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis.

Background & Aims: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Methods: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Results: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 µg/L efruxifermin vs. -3.4 µg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients. Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies. Lay summary: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH. Clinical Trial Number: NCT03976401.

Corn (Zea mays L) Boiled Water Provides Good Evidence for Lowering of Lipid Profile (HDL-C, LDL-C, Triglycerides, and Total Cholesterol) in Dyslipidemia

@#Introduction: Dyslipidemia is a significant factor in cardiovascular and other diseases. Corn can be used to treat dyslipidemia. This study is to determine the effect of boiled corn water on levels of HDL-C, LDL-C, triglycerides (TG), and total cholesterol (TC) in people with dyslipidemia in certain areas in Indonesia. Methods: We used a quasi-experimental pretest-posttest control group design. A sample of 40 people for each group was taken using a purposive sampling technique. The group was given the intervention of corn-boiled water @ 200cc twice daily for seven days. Blood lipid profile using fasting and examined by Fluorometric-enzymatic assay method. All procedures are carried out based on operational standards. Within-group comparisons used the Wilcoxon test, while between-group comparisons used the Mann-Whitney U and Independent T-Test. Results: The LDL-C control group experienced an increase of 65.1 mg/dL, and the entire group’s lipid profile variation showed no difference between the pretest and posttest (p>.05). The intervention group showed an increase in HDL-C (0.1 mg/dL), a decrease in LDL-C (30.2 mg/ dL), TG (27.0 mg/dL), and TC (35.6 mg/dL). Within-group comparison of the intervention group showed HDL-C (p.153), LDL-C (p.001), TG (p.023), and TC (p<.001). A between-group comparison showed HDL-C (p.101), LDL-C (p.034), TG (p.003), and TC (p.006). Conclusion: Whole corn boiled water provides good evidence that it is effective in lowering LDL-C, TG, and TC, as well as improving dyslipidemia in HDL-C patients. This intervention can be used as an alternative treatment for dyslipidemia in terms of nutrition.

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2 (51.7% of patients had eGFR <60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c ≥160mg/dL and 29.3% ≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Pathogenic gain-of-function mutations in the prodomain and C-terminal domain of PCSK9 inhibit LDL binding.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds and mediates endo-lysosomal degradation of low-density lipoprotein receptor (LDLR), limiting plasma clearance of cholesterol-rich LDL particles in liver. Gain-of-function (GOF) point mutations in PCSK9 are associated with familial hypercholesterolemia (FH). Approximately 30%-40% of PCSK9 in normolipidemic human plasma is bound to LDL particles. We previously reported that an R496W GOF mutation in a region of PCSK9 known as cysteine-histidine-rich domain module 1 (CM1) prevents LDL binding in vitro [Sarkar et al., J. Biol. Chem. 295 (8), 2285-2298 (2020)]. Herein, we identify additional GOF mutations that inhibit LDL association, localized either within CM1 or a surface-exposed region in the PCSK9 prodomain. Notably, LDL binding was nearly abolished by a prodomain S127R GOF mutation, one of the first PCSK9 mutations identified in FH patients. PCSK9 containing alanine or proline substitutions at amino acid position 127 were also defective for LDL binding. LDL inhibited cell surface LDLR binding and degradation induced by exogenous PCSK9-D374Y but had no effect on an S127R-D374Y double mutant form of PCSK9. These studies reveal that multiple FH-associated GOF mutations in two distinct regions of PCSK9 inhibit LDL binding, and that the Ser-127 residue in PCSK9 plays a critical role.

Cumplimiento de objetivos en pacientes adultos con diabetes mellitus tipo 1: tasa estimada de disposición de glucosa como marcador clínico / Achievement of objectives in adult patients with type 1 diabetes mellitus: estimated glucose disposition rate as a clinical marker

Resumen Introducción: las guías de práctica clínica en diabetes mellitus (DM) establecen objetivos clínicos precisos sobre el buen manejo de la enfermedad, pero poco se sabe sobre el adecuado cumplimiento en nuestro medio. El sobrepeso y el sedentarismo han generado estigmas de síndrome metabólico en la población con DM1. Objetivos: evaluar el cumplimiento en cinco de dichos criterios: HbA1c <7%, c-LDL ≤100 mg/dl, actividad física ≥3 veces/ semana, tensión arterial sistólica (TAS) <140 mm Hg y no tabaquismo, y su asociación con insulinorresistencia determinada por la tasa estimada de disposición de glucosa (TeDG). Materiales y métodos: en 415 DM1 ≥18 años, 52% mujer y una edad de 34,8±13,9 años, se evaluó HbA1c, c-LDL, frecuencia semanal de actividad física (AF) estructurada, TAS y tabaquismo actual. Se determinó el grado de asociación a género, edad, antigüedad de la DM, nivel de educación, cobertura médica, índice de masa corporal (IMC) y sensibilidad a la insulina medida a través de la TeDG. Las variables cualitativas se analizaron por test de chi. y las cuantitativas por test de ANOVA I con post hoc por test de Tukey. Un valor de p<0,05 se consideró estadísticamente significativo. En todos los casos se utilizó un intervalo de confianza del 95%. Resultados: el 94,8% presentó TAS <140 mm Hg, el 82,2% no tabaquismo actual, el 56,5% c-LDL ≤100 mg/dL, el 39% AF ≥3 veces/semana y el 20,3% HbA1c <7%. Solo 26 pacientes (6,2%) alcanzaron en forma combinada los cinco objetivos analizados. El cumplimiento de dichos objetivos se asoció a nivel de educación secundaria o mayor (p=0,002) y cobertura de salud con obra social o prepaga (p=0,002). Hubo asociación significativa entre la TeDG en quienes cumplieron los cinco objetivos (p=0,02) y en forma individual en cuatro de ellos (TAS, c-LDL, HbA1c y AF). Conclusiones: de los 415 pacientes evaluados, el 6,2% cumplió los cinco objetivos. Solo el control de la TAS, no fumar y un c-LDL <100 mg/dL lo cumplió la mayoría de los pacientes. Una HbA1c <7% fue el objetivo individual que presentó menor grado de cumplimiento.

Abstract Introduction: the clinical practice guidelines in diabetes mellitus (DM) establish precise clinical objectives for the good management of the disease, but little is known about adequate compliance in our environment. Being overweight and sedentary have generated stigmas of metabolic syndrome in the population with DM1. Objectives: to evaluate the compliance with 5 of these criteria: HbA1c <7%, c-LDL ≤100 mg/dL, physical activity (PA) ≥3 times/week, systolic blood preasure (SBP) <140 mm Hg, and no smoking and its association with insulin resistance determined by the estimated glucose disposition rate (eGDR). Materials and methods: in 415 DM1 ≥18 years, 52% women, age 34.8±13.9 years, HbA1c, c-LDL, weekly frequency of structured PA, SBP, and current smoking were evaluated. The degree of association with gender, age, age of DM, level of education, medical coverage, BMI, and insulin sensitivity measured through eGDR was determined. Qualitative variables were analyzed by chi-square test and quantitative variables by ANOVA I test and analysis post hoc by Tukey's test for multiple comparisons. A value of p<0.05 was considered statistically significant. A 95% confidence interval was used in all cases. Results: systolic BP <140 mm Hg presented 94.8%, current non-smoking 82.2%, c-LDL ≤ 100 mg/dL 56.5%, physical activity (PA) ≥3 times a week 39% and HbA1c <7% 20.3%. Only 26 patients (6.2%) achieved the 5 objectives analyzed in combination. The fulfillment of the 5 objectives was associated at the level of ≥ secondary education (p=0.002) and health coverage with social welfare or prepaid (p=0.002). There was a significant association between TeDG in those who fulfilled the 5 objectives (p=0.02) and individually in 4 of them (SPB, c-LDL, HbA1c, and PA). Conclusions: of the 415 patients evaluated in our study, only 6.2% met the 5 criteria under consideration. Only control of SBP, non-smoking and c-LDL <100 were complied with by the majority of the patients. HbA1c <7% was the individual objective with the lowest degree of compliance.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations / Artritis reumatoide, indicación de estatinas y objetivos lipídicos: Análisis según diferentes recomendaciones

Background: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA).Objectives(1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. Methods: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. Results: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. Conclusion: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.(AU)

Antecedentes: Se han propuesto diferentes estrategias para el manejo del riesgo cardiovascular en pacientes con artritis reumatoide (AR).Objetivos(1) estimar el riesgo cardiovascular mediante diferentes estrategias en pacientes con AR, analizando qué proporción de pacientes deberían recibir estatinas; (2) identificar cuántos pacientes alcanzaron los objetivos lipídicos recomendados. Métodos: Estudio de corte transversal. Se estimaron los puntajes QRISK-3, Framingham (ajustado por un factor multiplicador × 1,5), ASCVD y SCORE. Se analizaron las indicaciones de estatinas, según las guías NICE, el Consenso Argentino, las guías ACC/AHA 2018 y las nuevas directrices europeas. Se analizaron los objetivos de C-LDL. Resultados: Se incluyeron 420 pacientes; 24,7 y 48,7% de los pacientes en prevención primaria y secundaria recibían estatinas, respectivamente. El 19,4% de los pacientes con antecedentes cardiovasculares recibían estatinas de alta intensidad. Aplicando las guías ACC/AHA (basadas en el puntaje ASCVD), el Consenso Argentino (basado en el puntaje ajustado de Framingham), las pautas NICE (basadas en el QRISK-3) y las recomendaciones europeas (basadas en el SCORE), 26,9, 26,5, 41,1 y el 18,2% de la población eran elegibles para el tratamiento con estatinas, respectivamente. Siguiendo las nuevas recomendaciones europeas, 50, 46,2 y 15,9% de los pacientes con riesgo bajo-moderado, alto o muy alto lograron los objetivos lipídicos recomendados. Conclusión: Aplicando varias estrategias para el manejo de los lípidos en nuestra población, la estratificación del riesgo cardiovascular y la indicación de estatinas fueron diferentes. Se observó una brecha significativa entre la indicación de estatinas esperada y observada, logrando los objetivos de C-LDL muy pocos pacientes.(AU)

Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO) / Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO)

Antecedentes y objetivo : Describir las características clínicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab en las unidades de nefrología de España.Material y métodosEstudio retrospectivo, observacional y multicéntrico que incluye los pacientes que iniciaron tratamiento con evolocumab (desde febrero de 2016 a agosto de 2018) en 15 unidades de nefrología en España. Se revisaron las características demográficas y clínicas de los pacientes, el tratamiento hipolipemiante y la evolución de los perfiles lipídicos entre 24 semanas antes y 12±4 semanas después del inicio de evolocumab.ResultadosSe incluyeron 60 pacientes: 53,3% mujeres, edad media (DE) de 56,9 (12,8) años, el 45,0% con hipercolesterolemia familiar (HF) (5,0% homocigota y 40,0% heterocigota) y el 65,0% con enfermedad cardiovascular aterosclerótica (ECVA) previa. El filtrado glomerular estimado (FGe) medio fue de 62,6 (30,0) ml/min/1,73m2 (51,7% pacientes con FGe<60ml/min/1,73m2 [ERC estadio >2]), el 50,0% con proteinuria (>300mg/g) y el 10,0% con síndrome nefrótico. Otros factores de riesgo CV fueron: hipertensión (75,0%), diabetes mellitus (25,0%) y hábito tabáquico (21,7%). El 40,0% eran intolerantes a estatinas. Al inicio de evolocumab, el 41,7% tomaban estatinas de alta intensidad, el 18,3% estatinas de moderada intensidad y el 50,0% ezetimiba. Los niveles medios (DE) de c-LDL al inicio de evolocumab fueron de 179,7 (62,9) mg/dl (53,4% pacientes con c-LDL≥160mg/dl y 29,3%≥190mg/dl). Después de 12 semanas del tratamiento con evolocumab se observó una reducción de los niveles de c-LDL del 60,1%. A la semana 12, el 90,0% de los pacientes alcanzó niveles c-LDL<100mg/dl, 70,0%<70mg/dl y 55,0%<55mg/dl, mientras que el FGe medio y el uso de estatinas se mantuvieron estables. (AU)

Background and objective: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain.Material and methodsRetrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed.ResultsSixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable. (AU)

The benefits of the Mediterranean diet in first episode psychosis patients taking antipsychotics.

Background: The side effects of antipsychotics (APs), related to weight gain and metabolic disturbances, can contribute to the health burden of psychotic people. Objective: To explore a) the level of adherence to the Mediterranean Diet (MedDiet) and consumption of fermented foods by first episode of psychosis (FEPs) patients taking APs, in comparison to matched -for age and BMI- healthy controls (HCs), and b) the effect of this dietary pattern on the biochemical and metabolic profile of FEPs. Method: The study population consisted of 33 FEPs treated with APs for less than 5 years, with no history of other chronic diseases, and an equal number of HCs. The FEPs were classified into two subgroups, according to their AP medication, depending on the documented risk of weight gain. A validated questionnaire for the adherence to Mediterranean diet and a food frequency questionnaire for selected fermented foods were completed by FEPs and HC. Anthropometric data and blood measurements were recorded for all participants. Results and conclusions: The FEPs showed a relevant lower overall adherence to the MedDiet, but no differences in consumption of fermented foods. Type of antipsychotic therapy uncovered differences in platelet count, vitamin B12, HDL and glucose (p < 0.05) between the subgroups of FEPs and HCs, although no values were abnormal. The MedDiet score was found to act as a prognostic factor for abnormal glucose levels in FEPs treated with APs associated with weight gain (p = 0.04). These results need to be confirmed by observations after long term adherence to MedDiet.

Efecto selectivo de bypass gástrico laparoscópico en Y de Roux sobre el metabolismo lipídico / Selective effect of laparoscopic Roux-en-Y gastric bypass on lipid metabolism

INTRODUCCIÓN: La cirugía bariátrica (CB) ha mostrado reducir la morbilidad y mortalidad cardiovascular en obesidad mórbida. La CB ha mejorado la dislipemia del paciente insulinorresistente (IR). El objetivo de nuestro trabajo fue evaluar si existe diferencia en el perfil lipídico entre la técnica de bypass gástrico laparoscópico en Y de Roux (BGYRL) vs. la técnica de la gastrectomía tubular laparoscópica (GTL) a 18 meses de seguimiento. MÉTODOS: Estudio observacional, abierto, prospectivo, de pacientes con obesidad mórbida sometidos que realizaron a cirugía bariátrica a 18 meses seguimiento. Se realizaron análisis antropométricos, composición corporal, gasto energético de reposo, de glucosa, insulina, hemoglobina glucosilada (HbA1c), lipoproteínas de baja densidad (LDL), lipoproteínas de alta densidad (HDL), triglicéridos (TG) y colesterol total (CT). RESULTADOS: No se encontraron diferencias basales de la proporción de pacientes con hipertensión arterial, diabetes de tipo 2, esteatosis y de sexo entre los grupos de BGYRL (91) vs. GTL (77). Se observo reducción de TG a los seis meses a favor de BGYRL vs. GTL: 108,60± 34,86 vs. 124,59±44,58; p = 0,044), en cambio se encontró disminución tanto de niveles de LDL a los 12 y 18 meses a favor del grupo BGYRL vs. GTL: 96,23±24,33 vs. 107,83±28,88, p = 0,025; 90,98±20,62 vs. 106,22±31,48, p = 0,003; la disminución de CT se observó solo a los 18 meses a favor del grupo BGYRL vs. GTL: 171,39±25,058 vs. 186,89±31,81, p = 0,005.ConclusiónEl BGYRL ha mostrado ser más eficaz para reducir LDL y CT en comparación con GTL, lo cual otorga un beneficio adicional del BGYRL en relación al perfil lipídico del paciente.

INTRODUCTION: Bariatric surgery (BS) has shown to reduce cardiovascular morbidity and mortality in obesity. The BS has improved the dyslipidemia of the insulin resistant patient, our objective was to evaluate if there was a difference in the lipid profile between the laparoscopic roux-en-Y gastric bypass (RYGB) technique vs. the sleeve gastrectomy (SG) technique at 18 months of follow-up. METHODS: An observational, open, prospective study of morbidly obese patients who underwent bariatric surgery at 18-month follow-up. Anthropometric analysis, body composition, energy expenditure at rest, glucose, insulin, HbA1c, LDL, HDL, TG and CT were performed. RESULTS: Absence baseline differences were found in the proportion of patients with hypertension, diabetes, steatosis, and sex between the RYGB vs SG groups. A reduction of TG was observed at 6 months in favor of RYGB vs SG: 108.60±34.86 vs. 124.59±44.58, P = 0.044), however, a decrease in both LDL levels was found at 12 and 18 months in favor of the RYGB vs. SG group: 96.23±24.33 vs. 107.83±28.88, P = 0.025; 90.98±20.62 vs 106.22±31.48, P = 0.003; the decrease in CT was observed only at 18 months in favor of the RYGB vs. SG group: 171.39±25.058 vs. 186.89±31.81, P = 0.005. CONCLUSIONS: RYBG has shown to be more effective in reducing LDL and CT levels compared to SG, which provides an additional benefit of RYGB in relation to the lipid profile of the patient.

Selective effect of laparoscopic Roux-en-Y gastric bypass on lipid metabolism. / Efecto selectivo de bypass gástrico laparoscópico en Y de Roux sobre el metabolismo lipídico.

INTRODUCTION: Bariatric surgery (BS) has shown to reduce cardiovascular morbidity and mortality in obesity. The BS has improved the dyslipidemia of the insulin resistant patient, our objective was to evaluate if there was a difference in the lipid profile between the laparoscopic roux-en-Y gastric bypass (RYGB) technique vs. the sleeve gastrectomy (SG) technique at 18 months of follow-up. METHODS: An observational, open, prospective study of morbidly obese patients who underwent bariatric surgery at 18-month follow-up. Anthropometric analysis, body composition, energy expenditure at rest, glucose, insulin, HbA1c, LDL, HDL, TG and CT were performed. RESULTS: Absence baseline differences were found in the proportion of patients with hypertension, diabetes, steatosis, and sex between the RYGB vs SG groups. A reduction of TG was observed at 6 months in favor of RYGB vs SG: 108.60±34.86 vs. 124.59±44.58, P = 0.044), however, a decrease in both LDL levels was found at 12 and 18 months in favor of the RYGB vs. SG group: 96.23±24.33 vs. 107.83±28.88, P = 0.025; 90.98±20.62 vs 106.22±31.48, P = 0.003; the decrease in CT was observed only at 18 months in favor of the RYGB vs. SG group: 171.39±25.058 vs. 186.89±31.81, P = 0.005. CONCLUSIóN: RYBG has shown to be more effective in reducing LDL and CT levels compared to SG, which provides an additional benefit of RYGB in relation to the lipid profile of the patient.

Secular trends in serum lipid profiles in young adults in Norway, 2001-19.

Background: Lower prevalence of major cardiovascular disease (CVD) risk factors, such as dyslipidemia, hypertension and smoking, can explain a substantial part of the decline in CVD mortality and incidence for the past decades in Western countries. However, some studies have indicated less favorable trends in risk factors in recent years. We have assessed time trends in lipid profiles among young adults in Norway measured between 2001 and 2019. Methods: Samples of serum lipids analyzed at one large medical laboratory in Oslo, Norway, mainly requisitioned by primary care physicians, were analyzed cross-sectionally to estimate year-to-year trends among men and women aged 18-49 years. We also assessed the lipid distributions and proportions with adverse lipid levels. Results: In total, more than 2,6 million blood samples, comprising more than 1 million individuals (mean age 37.7 years) from all regions of Norway were included. All measures improved among all age groups in both women and men, especially in total and non-HDL cholesterol (-0.22 and -0.25 mmol/l per decade, respectively). There were downward shifts in the population distribution of total, non-HDL-C and LDL-C. The overall prevalences of total cholesterol ≥5.0 mmol/l and non-HDL-C ≥3.9 mmol/l similarly decreased, from ∼63 to 46% and from ∼52 to 34%, respectively. More than 1/3 had elevated levels of total and/or non-HDL-C in 2019. Conclusion: In a large proportion of the Norwegian population aged 18-49 years old, the lipid profiles improved during the last two decades. As the use of lipid-lowering medications is low in this age group, this likely reflects favorable secular trends.

Temporal trends of lipid control in very high cardiovascular risk patients.

INTRODUCTION: Since 2011, the European guidelines have included a specific low-density lipoprotein cholesterol (LDL-C) target, <70 mg/dl, for very high cardiovascular risk (CVR) patients. However, registries have shown unsatisfactory results in obtaining this level of adequate lipid control. OBJECTIVES: To assess temporal trends in the use of lipid-lowering therapy (LLT) and attainment of adequate control in very high CVR patients since 2011. METHODS: We performed a retrospective observational study including very high CVR patients admitted in two periods: the first two years since the 2011 guidelines (2011/2012) and five years later (2016/2017). Lipid values, LLT, clinical variables and adequate lipid control rates were analyzed. RESULTS: A total of 1314 patients were reviewed (2011/2012: 638; 2016/2017: 676). Overall, 443 patients (33.7%) were not under LLT and only a slight improvement in drug prescription was observed from 2011/2012 to 2016/2017. In LLT users, the proportion of high-intensity LLT increased significantly in the later years (6.4% vs. 24.0%; p<0.001), but this was not associated with adequate lipid control. Overall, mean LDL-C was 95.4±37.2 mg/dl and adequate control was achieved in 320 patients (24.4%), without significant differences between 2011/2012 and 2016/2017 (p=0.282). Independent predictors of adequate control were male gender, older age, diabetes, chronic kidney disease, prior acute coronary syndrome, prior stroke and LLT, while stable coronary artery disease was associated with higher risk of failure. CONCLUSION: Even after the introduction of specific LDL-C targets, these are still not reached in most patients. Over a five-year period, LLT prescription only improved slightly, while adequate lipid control rates remained unchanged.

Lipid profile of patients treated with evolocumab in Spanish hospital nephrology units (RETOSS NEFRO). / Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO).

BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. MATERIAL AND METHODS: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12±4 weeks post-initiation of evolocumab were reviewed. RESULTS: Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0)ml/min/1.73m2 (51.7% of patients had eGFR<60ml/min/1.73m2 [CKD stage>2]), 50.0% had proteinuria (>300mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9)mg/dL (53.4% of patients with LDL-c≥160mg/dL and 29.3%≥190mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100mg/dL, 70.0% <70mg/dL, and 55.0% <55mg/dL, while mean eGFR levels and statin use were remained stable. CONCLUSION: In Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

Lipid Monitoring After Initiation of Lipid-Lowering Therapies: Return of Performance Measures?

PURPOSE OF REVIEW: The 2015 American College of Cardiology (ACC)/American Heart Association (AHA) Focused Update of Secondary Prevention Lipid Performance Measures removed low-density lipoprotein cholesterol (LDL-C) assessment as a performance measure. This review discusses the evidence supporting the importance of lipid monitoring in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). RECENT FINDINGS: The 2018 AHA/ACC Multisociety cholesterol guideline (as did the 2013 guideline) recommends a lipid panel after initiating lipid-lowering therapy to monitor adherence and medication efficacy. The 2018 guideline also recommends adding nonstatin therapy in very-high-risk ASCVD patients with LDL-C ≥70 mg/dL despite maximally tolerated statin therapy. The removal of LDL-C monitoring as a performance measure is not consistent with the 2018 cholesterol guidelines. Given the importance of monitoring lipid-lowering medication efficacy and adherence and optimally reducing LDL-C in very-high-risk patients with additional evidence-based nonstatin therapy, LDL-C assessment after initiating lipid-lowering therapy should be reinstated as a performance measure for patients with ASCVD.

Clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia.

BACKGROUND: Abnormal lipid metabolism manifests as hypercholesterolemia in patients with obstructive jaundice due to lipoprotein X (LpX). Our aim was to explore the clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia in a large number of samples. METHODS: A total of 665 patients with obstructive jaundice were included and categorized into two groups (with/without dyslipidemia) based on the ratio of the sum of HDL-c and LDL-c to total cholesterol [(HDL-c + LDL-c)/TC] with a cut-off value of 0.695. Laboratory liver, kidney, and blood lipid parameters were determined. Cholesterol composition assessment was performed by ultracentrifugation and high-performance liquid chromatography (UC-HPLC), and serum protein profiles were analyzed by capillary electrophoresis. RESULTS: Liver function in patients with obstructive jaundice accompanied by dyslipidemia was more aggravated than that in patients with simple obstructive jaundice (P < 0.05). The (HDL-c + LDL-c)/TC ratio was negatively correlated with bilirubin levels (P < 0.05). In addition, the difference in ApoB/LDL-c ratios was statistically significant between the obstructive jaundice accompanied by dyslipidemia group and healthy control group (P < 0.05). The LDL-c concentration determined by the UC-HPLC method was more than five times that determined by the enzymatic method (P < 0.05). Bisalbuminemia was found in 43 of 60 patients with obstructive jaundice accompanied by hypercholesterolemia. CONCLUSIONS: In patients with obstructive jaundice, the decreased (HDL-c + LDL-c)/TC ratio may be a novel marker to identify dyslipidemia secondary to LpX. The decreased ratio was associated with poor liver function and indicated disease progression.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents?

INTRODUCTION AND OBJECTIVES: To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril). METHODS: This was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg and atorvastatin 40mg on SBP and LDL-C. The coprimary endpoints were differences in the adjusted mean 24-hour SBP (using ambulatory BP measurement) and LDL-C during the study period estimated using an ANCOVA model. RESULTS: Of the 241 patients included in the per protocol population, 84 received the CNIC polypill (group A), 84 atorvastatin (group B), and 73 ramipril (group C). SBP decreased from 139.3±12.5 to 133.2±12.9mmHg in group A and from 138.1±11.9 to 134.0±12.8mmHg in group C (baseline adjusted mean difference for the decrease in SBP was 1.77mmHg (90%CI, -0.5 to 4.0) in favor of group A, without reaching statistical significance. LDL-C was reduced by 33.9±21.6 and 29.2±25.8mg/dL in groups A and B, respectively (baseline adjusted mean difference for the decrease in LDL-C was 7.0% (90%CI, 1.5-12.4), a significantly greater decrease with the polypill). The 3 treatments were well tolerated. CONCLUSIONS: The results of this study rule out a negative effect on blood pressure of the interaction between the components of the CNIC polypill. The reduction in LDL-C was greater in the CNIC polypill group, suggesting a synergistic effect of the components.

Goal achievement of HbA1c and LDL-cholesterol in a randomized trial comparing colesevelam with ezetimibe: GOAL-RCT.

AIM: To compare the efficacy and safety of colesevelam and ezetimibe as second-line low density lipoprotein-cholesterol (LDL-c)-lowering options in type 2 diabetes (T2D). MATERIALS AND METHODS: GOAL-RCT is a 24-week, open-label, randomized, pragmatic clinical trial. Subjects with T2D with uncontrolled HbA1c (7.1%-10%) and LDL-c (>2.0 mmol/L) were randomized 1:1 to colesevelam 3.75 g or ezetimibe 10 mg daily. The primary composite outcome was the proportion of participants achieving an LDL-c target of ≤2.0 mmol/L and HbA1c target of ≤7.0%. Intention to treat analysis was performed. RESULTS: Two hundred subjects were enrolled: mean age 59 ± 10 years; mean HbA1c 8.0%; mean LDL-c 2.5 mmol/L; 97% on statin therapy. The primary composite outcome was achieved by similar proportions of participants with colesevelam (14.6%) and ezetimibe (10.5%) (Pnon-inferiority < .001, Psuperiority = .41). LDL-c reduction from baseline was less with colesevelam compared with ezetimibe (14.0% vs. 23.2%, P < .01), as was the proportion of subjects achieving an LDL-c target of ≤2.0 mmol/L (47.6% and 67.0%, respectively; P = .007). Mean HbA1c was reduced with colesevelam (-0.26 ± 0.10%), while no change was observed with ezetimibe (difference P = .06). Adverse events and discontinuation rates were higher for colesevelam (20.2% and 31.1%) compared with ezetimibe (7.2% and 6.2%), respectively. CONCLUSIONS: Among subjects with T2D, the initiation of colesevelam or ezetimibe led to similar achievement of primary composite outcome (LDL-c and HbA1c within target), with ezetimibe recording a greater LDL-c reduction and better tolerability than colesevelam.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.