Effect of PCSK9 inhibitors on remnant cholesterol and lipid residual risk: The LIPID-REAL registry.

BACKGROUND: Monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 55%, regardless of baseline treatments. Nonetheless, the effect of other lipid parameters, such as cholesterol remnants or, the so-called lipid residual risk, is unknown. METHODS: Multicenter and retrospective registry of patients treated with PCSK9 inhibitors from 14 different hospitals in Spain. Before and on-treatment lipid parameters were recorded. Residual lipid risk was estimated by (1) cholesterol remnants, (2) triglycerides/HDLc ratio (TG/HDL), (3) total cholesterol/HDLc (TC/HDL) and (4) the triglycerides-to-glucose index (TGGi). RESULTS: Six hundred fifty-two patients were analysed, mean age of 60.2 (9.63) years, 24.69% women and mean LDLc before treatment 149.24 (49.86) mg/dl. Median time to second blood determination was 187.5 days. On-treatment LDLc was 67.46 (45.78) mg/dl, which represented a 55% reduction. Significant reductions were observed for TG/HDL ratio, cholesterol remnants, TC/HDL ratio and TGGi. As consequence, 34.61% patients had LDLc <55 mg/dl and cholesterol remnants <30 mg/dl; additionally, 31.95% had cholesterol remnants <30 mg/dl but LDLc >55 mg/dl. Patients who had levels of cholesterol remnants >30 mg/dl before initiating the treatment with PCSK9 had higher reductions in cholesterol remnants, TG/HDL ratio, TC/HDL and TGGi. By contrast, no reduction differences were observed according to baseline LDLc (< or > the mean), age, gender or obesity. CONCLUSIONS: This multicenter and retrospective registry of real-world patients treated with PCSK9 inhibitors demonstrates a positive effect on cholesterol remnants and lipid residual risk beyond LDLc reductions.

Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry.

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Variación del perfil cardiometabólico en pacientes diabéticos obesos intervenidos de cirugía bariátrica. Cambios en el riesgo cardiovascular / Modification of cardiometabolic profile in obese diabetic patients after bariatric surgery: changes in cardiovascular risk

Introducción y objetivos. La cirugía bariátrica es una herramienta eficaz de control metabólico para pacientes obesos diabéticos. El objetivo de este trabajo es determinar la evolución del peso y el metabolismo glucídico y lipídico en pacientes obesos diabéticos intervenidos de cirugía bariátrica, durante los primeros 4 años tras la intervención. Métodos. Estudio retrospectivo de 104 pacientes (71 mujeres; media de edad, 53,0 ± 0,9 años; índice de masa corporal, 46,8 ± 0,7) con diabetes mellitus tipo 2 de una mediana de 3 años de evolución, a los que se practicó bypass gástrico proximal laparoscópico. Resultados. La glucemia y la concentración de glucohemoglobina descendieron durante los primeros 1-3 meses y se mantuvieron estables hasta los 4 años, lo que permitió eliminar el tratamiento hipoglucemiante al 80% de los pacientes. No observamos diferencias en función del índice de masa corporal, tiempo de evolución de la diabetes mellitus o el tratamiento antidiabético previo. El peso descendió hasta los 15-24 meses, con ligera recuperación posterior. Los valores de colesterol total, triglicéridos y lipoproteínas de baja densidad mejoraron significativamente, y se había obtenido valores objetivo en alrededor del 80% de los pacientes a partir de 12 meses. Estos descensos no se correlacionaron con los cambios de peso. Las lipoproteínas de alta densidad descendieron hasta los 12 meses, con una pequeña recuperación posterior, a pesar de lo cual el 85% de los pacientes presentaban valores objetivo 24 meses tras la cirugía. Conclusiones. La cirugía bariátrica es eficaz para el tratamiento de pacientes diabéticos obesos, mejora su control metabólico y reduce el riesgo cardiovascular (AU)

Introduction and objectives. Bariatric surgery is a valuable tool for metabolic control in obese diabetic patients. The aim of this study was to determine changes in weight and carbohydrate and lipid metabolism in obese diabetic patients during the first 4 years after bariatric surgery. Methods. A retrospective study was performed in 104 patients (71 women; mean age, 53.0 [0.9] years; mean body mass index, 46.8 [0.7]) with type 2 diabetes mellitus (median duration, 3 years) who underwent laparoscopic proximal gastric bypass. Results. Blood glucose levels and glycated hemoglobin concentrations decreased during the first 1-3 postoperative months. Values stabilized for the rest of the study period, allowing hypoglycemic treatment to be discontinued in 80% of the patients. No significant differences were observed as a function of the body mass index, diabetes mellitus duration, or previous antidiabetic treatment. Weight decreased during the first 15-24 months and slightly increased afterward. Levels of total cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and target values were reached after 12 months in 80% of the patients. No correlation was found between these reductions and weight loss. Similarly, high-density lipoprotein concentrations decreased until 12 months after surgery. Although concentrations showed a subsequent slight increase, target or lower high-density lipoprotein values were achieved at 24 months postintervention in 85% of the patients. Conclusions. Bariatric surgery is effective for the treatment of obese diabetic patients, contributing to their metabolic control and reducing their cardiovascular risk (AU)

Modification of cardiometabolic profile in obese diabetic patients after bariatric surgery: changes in cardiovascular risk.

INTRODUCTION AND OBJECTIVES: Bariatric surgery is a valuable tool for metabolic control in obese diabetic patients. The aim of this study was to determine changes in weight and carbohydrate and lipid metabolism in obese diabetic patients during the first 4 years after bariatric surgery. METHODS: A retrospective study was performed in 104 patients (71 women; mean age, 53.0 [0.9] years; mean body mass index, 46.8 [0.7]) with type 2 diabetes mellitus (median duration, 3 years) who underwent laparoscopic proximal gastric bypass. RESULTS: Blood glucose levels and glycated hemoglobin concentrations decreased during the first 1-3 postoperative months. Values stabilized for the rest of the study period, allowing hypoglycemic treatment to be discontinued in 80% of the patients. No significant differences were observed as a function of the body mass index, diabetes mellitus duration, or previous antidiabetic treatment. Weight decreased during the first 15-24 months and slightly increased afterward. Levels of total cholesterol, triglycerides, and low-density lipoprotein significantly decreased, and target values were reached after 12 months in 80% of the patients. No correlation was found between these reductions and weight loss. Similarly, high-density lipoprotein concentrations decreased until 12 months after surgery. Although concentrations showed a subsequent slight increase, target or lower high-density lipoprotein values were achieved at 24 months postintervention in 85% of the patients. CONCLUSIONS: Bariatric surgery is effective for the treatment of obese diabetic patients, contributing to their metabolic control and reducing their cardiovascular risk.