RESUMO
ABSTRACT: Low-density lipoprotein cholesterol (LDLc) is the lead effector of atherosclerosis and main treatment target. Bempedoic acid is a novel oral drug in the therapeutic armamentarium which is able to reduce LDLc. The objectives of this study were (1) to select the potential patients for administering bempedoic acid such as those with a very high cardiovascular risk in which objectives of LDLc were not achieved despite conventional treatment with PCSK9 inhibitors (PCSK9i) and/or statins and ezetimibe and (2) to estimate the cost-effectiveness of bempedoic acid in different scenarios. The methods used were a multicenter and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 17 different hospitals. Before and on-treatment LDLc cholesterol levels, medical treatments, clinical indication, and baseline characteristics were recorded. The results obtained from 443 subjects in secondary prevention were analyzed. The mean (±) LDLc level at baseline was 142.5 ± 46.4 mg/dL and 61.5 ± 40.5 mg/dL in the follow-up, with a reduction of 55.9% ( P < 0.0001); 71.6% of the patients reached the target of LDL < 55 mg/dL or >50% reduction. Of those patients treated with medium-intensity and low-intensity statins plus PCSK9 inhibitors (with or without ezetimibe), only 5.7% of them were able to reduce LDL below 55 mg/dL and the main LDLc reduction in this group was the lowest (42.9% on average). Patients with TG values >135 mg/dL represented 41.6% of the sample, of which approximately 10% of them were using fibrates. Assuming only LDLc reduction and the UK price, the incremental cost-effectiveness ratio was 88,359; 83,117; 82,378; and 79,015 for different discount rates. In conclusion, one-third of the patients could achieve the target LDL proposed in the 2019 ESC/EAS guidelines. Approximately 10% of them could also benefit from treating hypertriglyceridemia as indicated in the 2021 ESC guidelines on cardiovascular disease prevention. Patients with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe would be the most benefited. Bempedoic acid could be a not cost-efficacy therapy in all the scenarios, but we need to wait for the CLEAR OUTCOMES Trial results.
Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Análise de Custo-Efetividade , Ezetimiba/efeitos adversos , Fatores de Risco de Doenças Cardíacas , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
Assuntos
Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Colesterol , Triglicerídeos , Sistema de Registros , HDL-ColesterolRESUMO
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.
Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/efeitos adversos , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Sistema de Registros , Estudos Retrospectivos , Caracteres Sexuais , Fatores SexuaisRESUMO
BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Exercício Físico , Síndrome Metabólica/prevenção & controle , Comportamento de Redução do Risco , Comportamento Sedentário , Idoso , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Comportamento Alimentar , Feminino , Estado Funcional , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Valor Nutritivo , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Fatores de TempoRESUMO
GOALS: To explore affective and cognitive status, later in life, in individuals with and without previous history of eating disorder (ED), and also its association with higher risk for metabolic syndrome (MetS) symptomatology. METHODS: A cross-sectional analysis of 6756 adults, aged 55-75 years with overweight/obesity and MetS participating in the Predimed-Plus study was conducted. Participants completed self-reported questionnaires to examine lifetime history of ED, according to DSM-5 criteria, and other psychopathological and neurocognitive factors. Anthropometric and metabolic measurements were also collected. RESULTS: Of the whole sample, 24 individuals (0.35%) reported a previous history of ED. In this subsample, there were more women and singles compared to their counterparts, but they also presented higher levels of depressive symptoms and higher cognitive impairment, but also higher body mass index (BMI) and severe obesity, than those without lifetime ED. CONCLUSIONS: This is one of the first studies to analyse the cognitive and metabolic impact of a previous history of ED. The results showed that previous ED was associated with greater affective and cognitive impairment, but also with higher BMI, later in life. No other MetS risk factors were found, after controlling for relevant variables.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Síndrome Metabólica , Idoso , Índice de Massa Corporal , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/psicologia , Fatores de RiscoRESUMO
BACKGROUND: High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns. OBJECTIVES: The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk. METHODS: This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55-75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and <40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) according to tertiles of change in nut consumption. Secondary outcomes included changes in dietary and lifestyle characteristics. A generalized linear model was used to compare 1-y changes in features of MetS, weight, dietary intakes, and lifestyle characteristics across tertiles of change in nut consumption. RESULTS: As nut consumption increased, between each tertile there was a significant decrease in WC, TG, systolic blood pressure, weight, and BMI (P < 0.05), and a significant increase in HDL cholesterol (only in women, P = 0.044). The interaction effect between time and group was significant for total energy intake (P < 0.001), adherence to the Mediterranean diet (MedDiet) (P < 0.001), and nut consumption (P < 0.001). Across tertiles of increasing nut consumption there was a significant increase in extra virgin olive oil intake and adherence to the MedDiet; change in energy intake, on the other hand, was inversely related to consumption of nuts. CONCLUSIONS: Features of MetS and excess weight were inversely associated with nut consumption after a 1-y follow-up in the PREDIMED-Plus study cohort. This trial was registered at isrctn.com as ISRCTN89898870.
Assuntos
Dieta , Síndrome Metabólica/dietoterapia , Nozes , Sobrepeso/dietoterapia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Body weight dissatisfaction is a hindrance to following a healthy lifestyle and it has been associated with weight concerns. OBJECTIVES: The aim of this study was to assess the association between the adherence to the Mediterranean lifestyle (diet and exercise) and the desired body weight loss in an adult Mediterranean population with overweight. METHODS: Cross-sectional analysis in 6355 participants (3268 men; 3087 women) with metabolic syndrome and BMI (Body mass index) between 27.0 and 40.0 kg/m2 (55-75 years old) from the PREDIMED-Plus trial. Desired weight loss was the percentage of weight that participants wished to lose. It was categorized into four cut-offs of this percentage (Q1: <10%, n = 1495; Q2: 10-15%, n = 1804; Q3: <15-20%, n = 1470; Q4: ≥20%, n = 1589). Diet was assessed using a validated food frequency questionnaire and a 17-item Mediterranean diet questionnaire. Physical activity was assessed by the validated Minnesota-REGICOR and the validated Spanish version of the Nurses' Health Study questionnaire. RESULTS: Participants reporting higher percentages of desired weight loss (Q3 and Q4) were younger, had higher real and perceived BMI and were more likely to have abdominal obesity. Desired weight loss correlated inversely to physical activity (Q1: 2106 MET min/week; Q4: 1585 MET min/week. p < 0.001) and adherence to Mediterranean diet (Q1: 8.7; Q4: 8.3. p < 0.001). CONCLUSIONS: In older Mediterranean individuals with weight excess, desired weight loss was inversely associated with Mediterranean lifestyle adherence. Deeply rooted aspects of the MedDiet remained similar across groups. Longitudinal research is advised to be able to establish causality.
Assuntos
Dieta Mediterrânea , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Estilo de Vida Saudável , Sobrepeso/dietoterapia , Sobrepeso/psicologia , Cooperação do Paciente , Programas de Redução de Peso/métodos , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Índice de Massa Corporal , Cisplatino , Doxorrubicina , Exercício Físico/fisiologia , Feminino , Humanos , Peso Corporal Ideal , Ifosfamida , Masculino , Metotrexato , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Overall quality of dietary carbohydrate intake rather than total carbohydrate intake may determine the risk of cardiovascular disease (CVD). OBJECTIVE: We examined 6- and 12-mo changes in carbohydrate quality index (CQI) and concurrent changes in several CVD risk factors in a multicenter, randomized, primary-prevention trial (PREDIMED-Plus) based on an intensive weight-loss lifestyle intervention program. METHODS: Prospective analysis of 5373 overweight/obese Spanish adults (aged 55-75 y) with metabolic syndrome (MetS). Dietary intake information obtained from a validated 143-item semiquantitative food-frequency questionnaire was used to calculate 6- and 12-mo changes in CQI (categorized in quintiles), based on 4 criteria (total dietary fiber intake, glycemic index, whole grain/total grain ratio, and solid carbohydrate/total carbohydrate ratio). The outcomes were changes in intermediate markers of CVD. RESULTS: During the 12-mo follow-up, the majority of participants improved their CQI by increasing their consumption of fruits, vegetables, legumes, fish, and nuts and decreasing their consumption of refined cereals, added sugars, and sugar-sweetened beverages. After 6 mo, body weight, waist circumference (WC), systolic and diastolic blood pressure (BP), fasting blood glucose, glycated hemoglobin (HbA1c), triglyceride levels, triglycerides and glucose (TyG) index, and TyG-WC decreased across successive quintiles of improvement in the CQI. After 12 mo, improvements were additionally observed for HDL cholesterol and for the ratio of total to HDL cholesterol. Favorable improvements (expressed in common units of SD and 95% CI) for quintile 5 compared with quintile 1 of CQI change were observed for most risk factors, including TyG-WC (SD -0.20; 95% CI -0.26, -0.15), HbA1c (SD -0.16; 95% CI -0.23, -0.10), weight (SD -0.12; 95% CI -0.14, -0.09), systolic BP (SD -0.11; 95% CI -0.19, -0.02) and diastolic BP (SD -0.11; 95% CI -0.19, -0.04). CONCLUSIONS: Improvements in CQI were strongly associated with concurrent favorable CVD risk factor changes maintained over time in overweight/obese adults with MetS. This trial was registered as ISRCTN 89898870.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Carboidratos da Dieta/administração & dosagem , Sobrepeso , Idoso , Dieta/normas , Carboidratos da Dieta/classificação , Carboidratos da Dieta/normas , Ingestão de Energia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55-75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program.