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Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. Aim: To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. Conclusion: PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.
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Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 and 2016, the burden of CVD remains disproportionately higher in low- and middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at the prevention and treatment of CVD are currently available, poor adherence, early discontinuation of treatment, and suboptimal daily execution of the prescribed therapeutic regimes give rise to shortfalls in drug exposure, leading to high variability in the responses to the prescribed medications. Wald and Law, in their landmark paper published in BMJ 2003, hypothesized that the use of a fixed-dose combination of statins, ß-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin (classic Polypill composition) may increase adherence and decrease CVD by up to 80% when prescribed as primary prevention or in substitution of traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims to describe the available clinical trials performed to assess the impact of fixed-dose combinations on adherence, cost-effectiveness, and the risk factors critical to the onset of CVD.
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INTRODUCTION: Patients with psoriatic arthritis have some lipid metabolism changes and higher risk of metabolic syndrome (MetS) and cardiovascular diseases, regardless of traditional risk factors, suggesting that chronic inflammation itself plays a central role concerning the atherosclerosis. However, there is a lack of information regarding atherogenic pattern and lipoprotein subfractions burden in these individuals. AIM: To evaluate the HDL and LDL-cholesterol plasmatic levels and their subfractions after a nutritional intervention in patients with psoriatic arthritis (PsA). METHODS: This was a randomized, placebo-controlled clinical trial of a 12-week nutritional intervention. PsA patients were randomly assigned to 1-Placebo: 1 g of soybean oil daily, no dietetic intervention; 2-Diet + Supplementation: an individualized diet, supplemented with 604 mg of omega-3 fatty acids, three times a day; and 3-Diet + Placebo: individualized diet + 1 g of soybean oil. The LDL subfractions were classified as non-atherogenic (NAth), atherogenic (Ath) or highly atherogenic (HAth), whereas the HDL subfractions were classified as small, medium, or large particles, according to the current recommendation based on lipoproteins electrophoresis. RESULTS: A total of 91 patients were included in the study. About 62% of patients (n = 56) had an Ath or HAth profile and the main risk factors associated were male gender, longer skin disease duration and higher BMI. Thirty-two patients (35%) had a high-risk lipoprotein profile despite having LDL plasmatic levels below 100 mg/dL. The 12-week nutritional intervention did not alter the LDL subfractions. However, there were significant improvement of HDL subfractions. CONCLUSION: Recognizing the pro-atherogenic subfractions LDL pattern could be a relevant strategy for identifying PsA patients with higher cardiovascular risk, regardless total LDL plasmatic levels and disease activity. In addition, a short-term nutritional intervention based on supervised and individualized diet added to omega-3 fatty acids changed positively the HDLLARGE subfractions, while LDLLARGE subfraction was improved in hypercholesterolemic individuals. CLINICALTRIALS: gov identifier: NCT03142503 ( http://www. CLINICALTRIALS: gov/ ).
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Artrite Psoriásica , HDL-Colesterol , LDL-Colesterol , Humanos , Artrite Psoriásica/dietoterapia , Artrite Psoriásica/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , LDL-Colesterol/sangue , HDL-Colesterol/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Óleo de Soja/administração & dosagem , Aterosclerose/prevenção & controle , Aterosclerose/sangueRESUMO
INTRODUCTION: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases. OBJECTIVES: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months). METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures. STATISTICAL ANALYSIS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Sídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted. RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05). CONCLUSION: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.
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Glicemia , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Controle Glicêmico/métodos , Estudos Longitudinais , Glicemia/metabolismo , Fatores de Risco de Doenças Cardíacas , Hemoglobinas Glicadas/metabolismo , Doenças Cardiovasculares/prevenção & controle , Idoso de 80 Anos ou mais , Adulto Jovem , Índice de Massa Corporal , Adolescente , Pressão Sanguínea , Biomarcadores/sangue , Relação Cintura-Quadril , Circunferência da Cintura , Terapia Nutricional/métodosRESUMO
BACKGROUND: Low-density lipoprotein (LDL) cholesterol change with consumption of a low-carbohydrate diet (LCD) is highly variable. Identifying the source of this heterogeneity could guide clinical decision-making. OBJECTIVES: To evaluate LDL cholesterol change in randomized controlled trials involving LCDs, with a focus on body mass index (BMI) in kg/m2. METHODS: Three electronic indexes (Pubmed, EBSCO, and Scielo) were searched for studies between 1 January, 2003 and 20 December, 2022. Two independent reviewers identified randomized controlled trials involving adults consuming <130 g/d carbohydrate and reporting BMI and LDL cholesterol change or equivalent data. Two investigators extracted relevant data, which were validated by other investigators. Data were analyzed using a random-effects model and contrasted with results of pooled individual participant data. RESULTS: Forty-one trials with 1379 participants and a mean intervention duration of 19.4 wk were included. In a meta-regression accounting for 51.4% of the observed variability on LCDs, mean baseline BMI had a strong inverse association with LDL cholesterol change [ß = -2.5 mg/dL/BMI unit, 95% confidence interval (CI): -3.7, -1.4], whereas saturated fat amount was not significantly associated with LDL cholesterol change. For trials with mean baseline BMI <25, LDL cholesterol increased by 41 mg/dL (95% CI: 19.6, 63.3) on the LCD. By contrast, for trials with a mean of BMI 25-<35, LDL cholesterol did not change, and for trials with a mean BMI ≥35, LDL cholesterol decreased by 7 mg/dL (95% CI: -12.1, -1.3). Using individual participant data, the relationship between BMI and LDL cholesterol change was not observed on higher-carbohydrate diets. CONCLUSIONS: A substantial increase in LDL cholesterol is likely for individuals with low but not high BMI with consumption of an LCD, findings that may help guide individualized nutritional management of cardiovascular disease risk. As carbohydrate restriction tends to improve other lipid and nonlipid risk factors, the clinical significance of isolated LDL cholesterol elevation in this context warrants investigation. This trial was registered at PROSPERO as CRD42022299278.
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Dieta com Restrição de Gorduras , Sobrepeso , Adulto , Humanos , LDL-Colesterol , Triglicerídeos , HDL-Colesterol , Dieta com Restrição de Carboidratos , Colesterol , CarboidratosRESUMO
In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, pâ¯=â¯0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.
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Síndrome Coronariana Aguda , Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol , Pró-Proteína Convertase 9 , Inibidores de PCSK9 , Síndrome Coronariana Aguda/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Lipoproteína(a) , Anticolesterolemiantes/uso terapêuticoRESUMO
Background: Although the relationship between health status and dietary intake has been extensively studied in the general population, there is a lack of research that has specifically examined the association between frequency of breakfast consumption and cardiometabolic risk in university teachers. Objective: To determine the association between the frequency of breakfast consumption and cardiometabolic risk in university teachers. Methods: A cross-sectional study was conducted in 176 teachers from a private university located in the eastern region of Lima, Peru (Mage: 37.0 years; SD: 0.8, range: 24-59 years). The study was conducted during the period from December 2019 to February 2020. Information was collected on anthropometric and biochemical parameters and frequency of breakfast consumption. Multinomial logistic regression models were used to explore the association between frequency of breakfast with sociodemographic, anthropometric, and biochemical variables. Results: The highest prevalence of excess body weight (44.4%) was observed in those who consumed breakfast 0 to 2 days/week, but without statistical differences. Those who reported Low-density lipoprotein cholesterol (LDL-C) < 160 mg/dL were 77% less likely to fall into the 3-5 day/week breakfast frequency category than those who reported a regular frequency of breakfast (6 to 7 days/week) (Adjusted OR = 0.23, 95% CI 0.08 to 0.73; p < 0.05). In addition, teachers who reported a breakfast frequency of 3 to 5 days/week were 83% more likely to have a glucose concentration < 110 mg/dL compared to those who consumed breakfast of 6 to 7 days/week (Adjusted OR = 0.17, 95% CI 0.04 to 0.75; p < 0.05). Conclusion: Skipping breakfast for an extended period of time can have detrimental effects on cardiometabolic health. Promoting the benefits of breakfast could be a health message of great public health interest.
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AIM: To evaluate the impact of multicomponent integrated care (MIC) delivery program in a primary care real-life setting on diabetes care goals. METHODS: Patients with T2D and usual primary care from the public health system in Mexico were invited to participate in a five-month ambulatory MIC quality initiative (DIAbetes Empowerment and Improvement of Care program, DIABEMPIC). RESULTS: 841 patients who finished the program and with complete data were analyzed. The patients had a mean decrease in hemoglobin A1c, systolic and diastolic pressure, and LDL-cholesterol of 2.4%, 9 mmHg, 3 mmHg, and 22.5 mg/dL, respectively (p < 0.001). The achievement of the optimal triple target goal increased from 1.8% to 26.7% (p < 0.001). In the adjusted analysis, the diabetes knowledge and global self-care behavior score post-intervention, as well as the increment of global self-care behavior score were associated with the optimal composite risk factor control achievement. CONCLUSION: The incorporation of diabetes therapeutic education interventions to improve self-care behaviors along with adequate treatment intensification in diabetes care are fundamental to attaining optimal risk factor control and attenuating disease burden.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Melhoria de Qualidade , Hemoglobinas Glicadas , Pressão Sanguínea , Planejamento de Assistência ao Paciente , Atenção Primária à SaúdeRESUMO
Introdução: A síndrome metabólica é definida como um conjunto de condições clínicas que acometem cerca de 25% da população mundial e 29,6% dos brasileiros. Essa síndrome está relacionada ao aumento dos desfechos cardiovasculares, que podem ser preditos através do perfil lipídico. Compostos bioativos, tais como os ácidos graxos monoinsaturados (MUFA), são fortes aliados na prevenção desses desfechos. Um alimento importante por conter compostos bioativos e MUFA em abundância é o abacate. Há, porém, poucos estudos avaliando o efeito do óleo puro/virgem de abacate sobre o perfil lipídico em humanos com síndrome metabólica, e seus efeitos sobre os índices aterogênicos inexistem. Objetivo: O estudo buscou avaliar a suplementação de óleo de abacate sobre os níveis lipídicos e índices aterogênicos em pacientes portadores de síndrome metabólica. Método: 31 indivíduos adultos e obesos foram randomizados em grupo controle (óleo de soja) e grupo intervenção (óleo de abacate). Estes foram avaliados nos períodos pré e pós-intervenção (12 semanas) através de anamnese clínica e avaliação nutricional. Resultados: Observou-se que tanto o grupo controle quanto o grupo intervenção tinham a ingestão de lipídeos e gordura saturada maior que o recomendável. Quanto ao perfil lipídico e índices aterogênicos, não foi observada diferença significativa entre os períodos pré e pós. Conclusão: Os resultados podem ter se dado pela ausência do controle alimentar, sobrecarga de medicamentos, duração da intervenção, modo de administração e dose do suplemento. Logo, são necessários estudos futuros sobre os efeitos do óleo de abacate nessa população, que controlem melhor essas variáveis.
Introduction: Metabolic syndrome is defined as a set of clinical conditions that affect approximately 25% of the world's population and 29.6% of Brazilians. This syndrome is related to increased cardiovascular outcomes, which may be predicted by the lipid profile. Bioactive compounds, such as monounsaturated fatty acids (MUFAs), are strong allies in preventing these outcomes. Avocado is an important food because it contains abundant bioactive compounds and MUFAs. However, few studies evaluated the effects of pure/virgin avocado oil on the lipid profile in humans with metabolic syndrome, and its effects on atherogenic indices are not known. Objective:This study evaluated avocado oil supplementation on lipid levels and atherogenic indices in patients with metabolic syndrome. Method: Thirty-one obese adults were randomised into a control group (soybean oil) and an intervention group (avocado oil). These groups were evaluated in the pre- and post-intervention periods (12 weeks) via clinical anamnesis and nutritional assessment. Results: The control group and the intervention group had higher intakes of lipids and saturated fat than recommended. For the lipid profile and atherogenic indices, no significant difference was observed between the pre- and postintervention periods. Conclusion: These results may have been due to the absence of dietary control, medication overload, intervention duration, mode of administration and dose of the supplement. Therefore, future studies on the effects of avocado oil are needed in this population to better control these variables.