Perfil lipídico e fatores de risco para doenças cardiovasculares em idosos acompanhados na atenção primária à saúde / Lipid profile and risk factors for cardiovascular diseases in older people seen in primary health care / Perfil lipídico y factores de riesgo de enfermedades cardiovasculares en ancianos seguidos en la atención primaria de salud / Lipid profile and risk factors for cardiovascular diseases in older people seen in primary health care

Introdução: As dislipidemias estão entre os fatores de riscos mais importantes para o desenvolvimento de doenças cardiovasculares (DCV), além de estarem relacionadas a outras patologias que predispõem às DCV. Em função da elevada prevalência e da incidência de complicações associadas à cronicidade da doença, as dislipidemias representam elevados custos ao setor da saúde e da previdência social. Diante disso, ressalta-se a importância do Sistema Único de Saúde, representado pela Atenção Primária à Saúde (APS), em prover práticas de prevenção, diagnóstico e acompanhamento dos pacientes dislipidêmicos, a fim de desonerar o sistema financeiro e promover o envelhecimento saudável. Objetivo: Descrever a prevalência de perfil lipídico alterado entre os idosos. Além disso, pretendeu-se caracterizar a amostra quanto aos aspectos sociodemográficos, de saúde e de comportamento, bem como analisar os fatores associados à distribuição do perfil lipídico alterado e às características da amostra. Métodos: Estudo transversal com dados secundários, obtidos de agosto de 2021 a julho de 2022, tendo como população pacientes idosos em acompanhamento na APS do município de Marau (RS). Todos os dados foram coletados dos prontuários eletrônicos da rede de APS e, após dupla digitação e validação dos dados, a amostra foi caracterizada por meio de estatística descritiva. Foi calculada a prevalência de perfil lipídico alterado com intervalo de confiança de 95% (IC95%) e foi verificada sua distribuição conforme as variáveis de exposição, empregando-se o teste do χ2 e admitindo-se erro tipo I de 5%. Resultados: A prevalência de dislipidemia proporcional entre os sexos foi maior no feminino (33%). A cor de pele predominante foi a branca (76,7%). Cerca de 20% dos pacientes apresentavam colesterol total, colesterol HDL-c e triglicerídeos alterados, enquanto cerca de 15% apresentavam o colesterol HDL-c anormal. Constatou-se que os pacientes dislipidêmicos apresentam mais diabetes e hipertensão em relação aos não dislipidêmicos, ocorrendo a sinergia de fatores de risco para as DCV. Conclusões: A caracterização exercida neste estudo serve de base científica para a compreensão da realidade local e, também, para o direcionamento de políticas públicas na atenção primária que atuem de forma efetiva na prevenção e no controle das dislipidemias e demais fatores de risco cardiovascular.

Introduction: Dyslipidemias are among the most important risk factors for the development of cardiovascular diseases (CVD), in addition to being related to other pathologies that predispose to CVD. Because of the high prevalence and incidence of complications associated with the chronicity of the disease, dyslipidemias represent high costs for the health and social security sector. This highlights the importance of the Unified Health System, represented by primary health care (PHC), in providing prevention, diagnosis and follow-up practices for dyslipidemic patients to relieve the financial system and promote healthy aging. Objective: The study aimed to describe the prevalence of altered lipid profile among older people. In addition, we sought to characterize the sample in terms of sociodemographic, health and behavioral aspects, as well as to analyze the factors associated with the distribution of the altered lipid profile and the characteristics of the sample. Methods: We conducted a cross-sectional study with secondary data, from August 2021 to July 2022, with older patients being followed up at the PHC in the city of Marau (RS) as the study population. All data were collected from the electronic medical records of the PHC network, and after double-typing and validation, the sample was characterized using descriptive statistics. The prevalence of altered lipid profile was determined with a 95% confidence interval (95%CI), and its distribution was verified according to the exposure variables, using the chi-square test and a type I error of 5%. Results: The prevalence of proportional dyslipidemia between sexes was higher in females (33%). The predominant skin color was white (76.7%). About 20% of the patients had altered total cholesterol, HDL-C and triglycerides, while about 15% had abnormal HDL-C. It was found that more dyslipidemic patients had diabetes and hypertension than non-dyslipidemic patients, with a synergy of risk factors for CVD. Conclusions: The characterization carried out in this study serves as a scientific basis for understanding the local reality and also for directing public policies in PHC that act effectively in the prevention and control of dyslipidemia and other cardiovascular risk factors.

Introducción: las dislipidemias se encuentran entre los factores de riesgo más importantes para el desarrollo de enfermedades cardiovasculares (ECV), además de estar relacionadas con otras patologías que predisponen a ECV. Debido a la alta prevalencia e incidencia de complicaciones asociadas a la cronicidad de la enfermedad, las dislipidemias representan altos costos para los sectores de salud y seguridad social. Frente a eso, se destaca la importancia del Sistema Único de Salud, representado por la Atención Primaria de Salud (APS), en la provisión de prácticas de prevención, diagnóstico y seguimiento de pacientes dislipidémicos, con el fin de descongestionar el sistema financiero y promover el envejecimiento saludable. Objetivo: El estudio tiene como objetivo describir la prevalencia del perfil lipídico alterado entre los ancianos. Además, se pretende caracterizar la muestra en cuanto a aspectos sociodemográficos, de salud y conductuales, así como analizar los factores asociados a la distribución del perfil lipídico alterado y las características de la muestra. Métodos: estudio transversal con datos secundarios, de agosto de 2021 a julio de 2022, con pacientes ancianos en seguimiento en la APS del municipio de Marau (RS) como población. Todos los datos fueron recolectados de la historia clínica electrónica de la red de la APS y, luego de doble digitación y validación, la muestra fue caracterizada mediante estadística descriptiva. Se calculó la prevalencia de perfil lipídico alterado con un intervalo de confianza del 95% (IC95%) y se verificó su distribución según las variables de exposición, utilizando la prueba de chi-cuadrado y admitiendo un error tipo I del 5%. Resultados: la prevalencia de dislipidemia proporcional entre sexos fue mayor en el sexo femenino (33%). El color de piel predominante fue el blanco (76,7%). Alrededor del 20% de los pacientes tenían colesterol total, colesterol HDL-C y triglicéridos alterados, mientras que alrededor del 15% tenían colesterol HDL-C anormal. Se encontró que los pacientes dislipidémicos tienen más diabetes e hipertensión que los pacientes no dislipidémicos, con una sinergia de factores de riesgo para ECV. Conclusiones: la caracterización realizada en este estudio sirve de base científica para comprender la realidad local y también para orientar políticas públicas en atención primaria que actúen de manera efectiva en la prevención y control de la dislipidemia y otros factores de riesgo cardiovascular.

Associations of the PPARα and Lipoprotein Lipase Enzyme Gene Polymorphisms with Dyslipidemia in Obese and Non-obese Males.

Background: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear transcription factor responsible for gene expression, particularly those associated with lipid metabolism. The lipoprotein lipase enzyme (LPL) is considered a key enzyme in lipid metabolism and transport. The link between dyslipidemia and obesity is well understood. Dyslipidemia is also an established risk feature for cardiovascular disease. Thus, it becomes progressively essential to identify the role of genetic factors as risk markers for the development of dyslipidemia among obese males. Methods: A case-control study was performed including 469 males. Anthropometric characteristics and serum lipid profiles such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were evaluated. Genomic DNA extraction and purification were performed using whole blood samples. Restriction enzyme fragment length polymorphism was used to genotype PPARα and LPL single nucleotide polymorphisms. The associations between these polymorphisms and dyslipidemia were examined. Results: The CC and CG genotypes of PPARα gene polymorphisms were significantly associated with higher TC and LDL-C levels (P<0.05). The TT genotype of the LPL gene polymorphism was significantly associated with higher TG levels and lower HDL-C levels (P<0.05). In contrast, the GG genotype may have a protective action against dyslipidemia. Conclusion: The study reaches the interesting conclusion that there was a significant association between PPARα as well as LPL gene polymorphisms and dyslipidemia among obese and non-obese males.

Effects of Different Physical Training Protocols on Metabolic Syndrome Indicators and the Activity of Butyrylcholinesterase in Adolescents: A Randomized Clinical Trial.

Metabolic syndrome (MS) increases the risk of cardiovascular disease and affects children and adolescents. Butyrylcholinesterase (BChE) is an enzyme associated with obesity. The aim of this study was to investigate the effects of different physical training protocols on MS indicators and their relationship with BChE activity. This randomized clinical trial included 80 adolescents randomly assigned to 4 groups (CG: Control Group; ATG: Aerobic Training Group; STG: Strength Training Group; and CTG: Concurrent Training Group). The EFC, lipid profile, glycemia, waist circumference, and blood pressure were analyzed. With the exception of the CG, all the groups underwent training protocols for 12 consecutive weeks, 4 times a week, as follows: (ATG: 75% of heart rate on an electric treadmill; STG: 85% of 1 maximum repetition; CTG: 20 min of aerobic training at the same intensity as the ATG, and 20 min of resistance training in the same way as the STG). The training reduced MS-related biomarkers, such as the lipid profile, glycemia, waist circumference, and blood pressure. STG reduced BChE activity. The training methods led to improvements in the majority of the MS indicators. In addition, aerobic training significantly reduced BChE activity after a 12-week training protocol. The results suggest that different types of exercise can benefit MS.

Mechanistic Insights into Metabolic Function of Dynamin-Related Protein 1 (DRP1).

DRP1 plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue-specific DRP1 KO mice challenged with an HFD. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and ER-lipid droplet cross-talk in normal mice. Loss-of-function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, DRP1 deficiency induced the retention of nascent lipid droplets in ER, leading to perturbed overall lipid dynamics in the KO mice. Collectively, dysregulation of the dynamics of mitochondria, ER, and lipid droplets contributes to whole-body metabolic disorders, as evidenced by perturbations in energy metabolites. Our findings demonstrate that DRP1 plays a pivotal role in energy homeostasis in adipose tissue during obesity.

The effect of sumac on cardiovascular risk factors in adults: A systematic review and meta-analysis of randomized controlled trials.

Clinical evidence suggests the beneficial effects of sumac on cardiovascular risk factors. However, these results are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of sumac supplementation on cardiovascular risk factors in adults. The PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to 30 December 2023 to identify RCTs that were published in English. Data were presented as weighted mean difference (WMD) and associated 95 % confidence interval (CI). The quality of the included trials was measured using the Cochrane Collaboration's modified risk of bias tool. A pooled analysis of 16 trials showed that sumac consumption led to a significant reduction in fasting blood glucose (WMD: -6.03 mg/dl; 95 % CI: -9.67 to -2.39), hemoglobin A1c (WMD: -0.45 %; 95 % CI: -0.59 to -0.31), triglycerides (WMD: -9.07 mg/dL; 95 % CI: -16.19 to -1.94), low-density lipoprotein cholesterol (WMD: -5.58 mg/dL; 95 % CI: -11.27 to -0.12), BMI (WMD: -0.22 kg/m2; 95 % CI: -0.38 to -0.05), weight (WMD: -0.85 kg; 95 % CI: -1.44 to -0.27), waist circumference (WMD: -0.54 cm; 95 % CI: -0.92 to -0.15), and diastolic blood pressure (WMD: -2.72 mmHg; 95 % CI: -4.16 to -1.29). High-density lipoprotein-cholesterol level also increased significantly (WMD: 3.69 mg/dL; 95 % CI: 1.81-5.57). The overall results support possible protective and therapeutic effects of sumac on cardiovascular risk factors in adults. Additional prospective studies are suggested using longer intervention periods and higher supplementation doses to confirm these results.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

The Cashew Pseudofruit (Anacardium occidentale): Composition, Processing Effects on Bioactive Compounds and Potential Benefits for Human Health.

The fruit of the cashew, a tree belonging to the family Anacardiaceae, is composed of approximately 10% nut (cashew) and 90% stalk or pseudofruit, usually discarded in situ and fermented in the soil. This review identifies cashew pseudofruit's physicochemical characteristics and bioactive compounds and their possible relationship to health benefits. Different processing techniques have been used to preserve the pseudofruit, and the effect of these techniques on its nutrients is also reviewed in this work. Cashew is a highly perishable product with moisture content above 80% w/w and 10% w/w sugars. It also has a high content of polyphenols, flavonoids, and tannins and high antioxidant properties that are best preserved by nonthermal processing techniques. The pseudofruit presents the high inhibitory activity of α-amylase and lipase enzymes, has anti-inflammatory and body weight reduction properties and healing activity, and controls glucose levels, insulinemia, and insulin resistance. For all these reasons, cashews have been promoted as a propitious food/ingredient for preventive and therapeutic management of different pathologies such as diabetes, dyslipidemia, obesity, hypertension, fatty liver, and acne. Moreover, it has positive effects on the intestinal microflora, among others. This pseudofruit has a high potential for the development of functional foods.

Age and estimated glomerular filtration rate in Chinese older adults: a cohort study from 2014 to 2020.

Objectives: This study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age. Methods: This observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60-104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years. Results: The median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women's eGFR decreased by 1.06 mL/min/1.73 m2 and men's by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR. Conclusion: The eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

Effect of a Low-Glycemic Index Nutritional Intervention on Body Weight and Selected Cardiometabolic Parameters in Children and Adolescents with Excess Body Weight and Dyslipidemia.

Excess body weight in pediatric patients and the resulting dyslipidemia, if left untreated, are a serious risk factor for cardiovascular disease in young adults. Despite this, there is still no effective and validated nutritional strategy for the treatment of overweight/obesity and comorbid dyslipidemia in children and adolescents. A low-glycemic index (LGI) diet may be recommended, but evidence for its effectiveness in the pediatric population is limited. The aim of this study was to evaluate the effectiveness of nutritional intervention in children and adolescents with excess body weight and dyslipidemia. The study was conducted in patients aged 8-16 with overweight or obesity and lipid disorders (n = 64), of which 40 participants who completed the entire 8-week study were included in the analysis. Patients were randomly selected and allocated to one of the two dietary groups: the LGI diet or the standard therapy (ST) diet. Both diets were based on the principal recommendation of Cardiovascular Health Integrated Lifestyle Diet-2 (CHILD-2). This study showed that both LGI and ST diets were equally beneficial in reducing body weight, body fat, blood pressure, total cholesterol (TC), and triglyceride (TG) levels. The LGI diet, compared to the ST diet, was less effective in reducing blood TG levels but more effective in reducing diastolic blood pressure (DBP). Therefore, the choice of the type of diet in the treatment of children and adolescents with excess body weight and dyslipidemia may be individual. However, it should be based on the recommendation of CHILD-2. Further long-term, larger-scale studies are needed.

Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1-/-Ldlr-/- mice.

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na+ taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models. In humans, a genetic loss-of-function variant of NTCP has been associated with reduced plasma cholesterol levels. Here, we aimed to assess if Bulevirtide treatment attenuates atherosclerosis development by treating female Ldlr-/- mice with Bulevirtide or vehicle for 11 weeks. Since this did not result in the expected increase in plasma bile salt levels, we generated Oatp1a1-/-Ldlr-/- mice, an atherosclerosis-prone model with human-like hepatic bile salt uptake characteristics. These mice showed delayed plasma clearance of bile salts and elevated bile salt levels upon Bulevirtide treatment. At the study endpoint, Bulevirtide-treated female Oatp1a1-/-Ldlr-/- mice had reduced atherosclerotic lesion area in the aortic root that coincided with lowered plasma LDL-c levels, independent of intestinal cholesterol absorption. In conclusion, Bulevirtide, which is considered safe and is EMA-approved for the treatment of Hepatitis D, reduces atherosclerotic lesion area by reducing plasma LDL-c levels. We anticipate that its application may extend to atherosclerotic cardiovascular diseases, which warrants clinical trials.

Automated preparation of plasma lipids, metabolites, and proteins for LC/MS-based analysis of a high-fat diet in mice.

Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction platform that generates accurate, precise, and reproducible samples for metabolomic, lipidomic, and proteomic analyses from a single aliquot of plasma while minimizing hands-on time and avoiding contamination from plasticware. We applied mass spectrometry to examine the metabolome, lipidome, and proteome of 90 plasma samples to determine the effects of age, time of day, and a high-fat diet in mice. From 25 µl of mouse plasma, we identified 907 lipid species from 16 different lipid classes and subclasses, 233 polar metabolites, and 344 proteins. We found that the high-fat diet induced only mild changes in the polar metabolome, upregulated apolipoproteins, and induced substantial shifts in the lipidome, including a significant increase in arachidonic acid and a decrease in eicosapentaenoic acid content across all lipid classes.

Effect on blood lipids and body composition of a high-fat (MUFA) and high-fiber diet: A case-control study.

Metabolic Syndrome (MetS) is a constellation of risk factors including abdominal obesity, high triglycerides, low HDL cholesterol (HDL-C), elevated blood pressure, and elevated fasting glucose. In Spain, according to WHO criteria, the MetS prevalence is shown to be 32% in men and 29% in women. The role of dietary habits is one of the main therapeutic strategies for the management of MetS but the most effective dietary pattern has not been established yet. This study aimed to analyze the effect of on body composition, serum lipids, and MetS components of a high-MUFA and high-fiber diet (HMFD). A case-control study was performed considering 40 cohabiting women. Participants were randomly assigned to HMFD group or high mono-unsaturated diet (HMD) group to receive one of the two proposed dietary interventions. All data (serum lipids, blood pressure, height, weight, body composition, and waist circumference) were collected fasting at baseline, 55, 98, and 132 days. The HMFD group showed higher decrease in waist circumference than in the HMD group. LDL-C dropped in both groups. Triglycerides in the HMFD group dropped during the intervention, but once the intervention was over, they returned to baseline values. The mean systolic blood pressure was lower in HMFD group. A HMFD from a weekly consumption of processed meat (Torrezno de Soria) deeply fried in extra virgin olive oil in combination with vegetables logged in a Mediterranean diet can improve MetS risk factors in healthy overweight women.

Overlapping Pattern of the Four Individual Components of Dyslipidemia in Adults: Analysis of Nationally Representative Data.

Background/Objectives: Dyslipidemia is a well-established risk factor for cardiovascular disease (CVD). However, among available drug treatments, only those targeted at lowering LDL-C and consequently TC have demonstrated efficacy in preventing CVD. This is to say that the benefit for those with isolated high TG or low HDL-C is limited. The objective of this study is to examine the overlapping pattern of the four dyslipidemia components in US adult populations, which is important for quantifying the proportion of those who are less likely to benefit from lipid-lowering drugs and for a more precise use of the drug. Methods: A total of 7822 participants aged over 20 with abnormalities in any of the four lipid parameters, excluding those on lipid-lowering medications, were included from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 1999-2000 through 2017-2018. The proportions of different combinations of them were calculated and presented using area-proportional Euler plots. Results: High TC, high LDL-C, high TG, and low HDL-C were seen in 32.8% (95% CI: 31.3%-34.2%), 28.1% (95% CI: 26.6%-29.6%), 26.7% (95% CI: 25.4%-28.0%), and 65.9% (95% CI: 64.0%-67.7%) of the people with dyslipidemia, respectively. The proportions of dyslipidemia cases attributable to "high LDL-C or high TC" (irrespective of HDL-C and TG levels), "normal LDL-C, normal TC, but high TG" (irrespective of HDL-C level), and "normal LDL-C, normal TC, normal TG, but low HDL-C" (i.e., isolated low HDL-C) accounted for 37.5% (95% CI: 35.9%-39.1%), 18.3% (95% CI: 17.2%-19.4%), and 44.2% (95% CI: 42.5%-46.0%), respectively. Conclusions: Some two-thirds of those with dyslipidemia had low HDL-C or high TG but normal LDL-C and normal TC. As these people are less likely to benefit from currently available drug treatments in terms of CVD prevention, it is important to identify other effective strategies or interventions targeted at them in order to achieve more precise and cost-effective management of dyslipidemia.

Genetic Architecture and Clinical Outcomes of Combined Lipid Disturbances.

BACKGROUND: Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics of combined lipid disturbances in a general population-based cohort. METHODS: Among UK Biobank participants without prevalent coronary artery disease, we used blood lipid and apolipoprotein B concentrations to ascribe individuals into 1 of 6 reproducible and mutually exclusive dyslipoproteinemia subtypes. Incident coronary artery disease risk was estimated for each subtype using Cox proportional hazards models. Phenome-wide analyses and genome-wide association studies were performed for each subtype, followed by in silico causal gene prioritization and heritability analyses. Additionally, the prevalence of disruptive variants in causal genes for Mendelian lipid disorders was assessed using whole-exome sequence data. RESULTS: Among 450 636 UK Biobank participants: 63 (0.01%) had chylomicronemia; 40 005 (8.9%) had hypercholesterolemia; 94 785 (21.0%) had combined hyperlipidemia; 13 998 (3.1%) had remnant hypercholesterolemia; 110 389 (24.5%) had hypertriglyceridemia; and 49 (0.01%) had mixed hypertriglyceridemia and hypercholesterolemia. Over a median (interquartile range) follow-up of 11.1 (10.4-11.8) years, incident coronary artery disease risk varied across subtypes, with combined hyperlipidemia exhibiting the largest hazard (hazard ratio, 1.92 [95% CI, 1.84-2.01]; P=2×10-16), even when accounting for non-HDL-C (hazard ratio, 1.45 [95% CI, 1.30-1.60]; P=2.6×10-12). Genome-wide association studies revealed 250 loci significantly associated with dyslipoproteinemia subtypes, of which 72 (28.8%) were not detected in prior single lipid trait genome-wide association studies. Mendelian lipid variant carriers were rare (2.0%) among individuals with dyslipoproteinemia, but polygenic heritability was high, ranging from 23% for remnant hypercholesterolemia to 54% for combined hyperlipidemia. CONCLUSIONS: Simultaneous assessment of multiple lipid derangements revealed nuanced differences in coronary artery disease risk and genetic architectures across dyslipoproteinemia subtypes. These findings highlight the importance of looking beyond single lipid traits to better understand combined lipid and lipoprotein phenotypes and implications for disease risk.

Applicability of Artificial Intelligence in the Field of Clinical Lipidology: A Narrative Review.

The development of advanced technologies in artificial intelligence (AI) has expanded its applications across various fields. Machine learning (ML), a subcategory of AI, enables computers to recognize patterns within extensive datasets. Furthermore, deep learning, a specialized form of ML, processes inputs through neural network architectures inspired by biological processes. The field of clinical lipidology has experienced significant growth over the past few years, and recently, it has begun to intersect with AI. Consequently, the purpose of this narrative review is to examine the applications of AI in clinical lipidology. This review evaluates various publications concerning the diagnosis of familial hypercholesterolemia, estimation of low-density lipoprotein cholesterol (LDL-C) levels, prediction of lipid goal attainment, challenges associated with statin use, and the influence of cardiometabolic and dietary factors on the discordance between apolipoprotein B and LDL-C. Given the concerns surrounding AI techniques, such as ethical dilemmas, opacity, limited reproducibility, and methodological constraints, it is prudent to establish a framework that enables the medical community to accurately interpret and utilize these emerging technological tools.

Methodological quality and clinical recommendations of guidelines on the management of dyslipidaemias for cardiovascular disease risk reduction: a systematic review and an appraisal through AGREE II and AGREE REX tools.

BACKGROUND: Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations. METHODS: A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis. RESULTS: Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs. CONCLUSION: High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.

Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress.

BACKGRUOUND: This study investigates the impact of fluctuating lipid levels on endothelial dysfunction. METHODS: Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 µM, and in a variability group alternating between 0 and 100 µM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 µM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay. RESULTS: Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression. CONCLUSION: Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

Impact of Metabolic Syndrome and Cardiovascular Risk on the Quality of Life of People Living with HIV.

BACKGROUND: The time elapsed since HIV infection diagnosis (TdiagHIV) affects the quality of life (QoL) and can get worse when chronic illnesses start. OBJECTIVE: The aim of this study was to analyze the impact of metabolic syndrome (MetS) and cardiovascular risk (CVR) on the QoL of people living with HIV (PLHIV). METHODS: Cross-sectional study, with 60 PLHIV followed at a Reference Center in the city of Jataí, Goiás, Brazil. Data collection involved sociodemographic, clinical, CVR, MetS, and QoL information. The data were analyzed using descriptive and inferential statistics, with the BioEstat 5.3 program adopting p<0.05. RESULTS: There was a predominance of men (61.7%), aged ≤38 years (53.3%), with a TdiagHIV of 97.88±85.65 months and use of antiretroviral therapy (ART) of 80.13±69.37 months. The worst domain of QoL was concern about confidentiality (40 points), and the best was medication concerns (95 points). MetS predominated at 18.3% and a moderate CVR at 11.7%. MetS was positively associated with age >38 years, the female sex, with the lowest score in QoL for general function, and the highest for TdiagHIV and the use of ART (p<0.05). A moderate CRV was positively related to higher TdiagHIV and ART use, and low HDL-c, and the lowest score for QoL was found for trust in a professional (p<0.05). CONCLUSION: PLHIV who are older, have a higher TdiagHIV, and use ART are more likely to develop MetS and moderate CVR. The presence of these diseases in PLHIV causes impairment in areas of QoL.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.