Riesgo cardiovascular, dislipemias e indicación de estatinas en una población de obesos mórbidos

Introducción: La obesidad se relaciona con un riesgo cardiovascular (RCV) elevado. Esto nos obliga a tomar conductas terapéuticas y prevencionistas. El objetivo de este trabajo es evaluar el riesgo cardiovascular en una población de obesos mórbidos y valorar la correcta indicación de estatinas. Metodología: Estudio transversal, descriptivo, observacional, con la población obesos mórbidos del Programa de Obesidad y Cirugía Bariátrica (POCB) del Hospital Maciel, desde noviembre del 2014 a marzo del 2020. El RCV se valoró con la calculadora de la organización panamericana de la salud. La indicación de estatinas se consideró según RCV o diagnóstico de dislipemia. Resultados: Se analizaron 478 pacientes, el 84.3% fueron mujeres, la mediana para la edad fue de 44 años, y para el IMC 50 kg/m2. Se calculó un RCV bajo para el 57% de los pacientes; y alto o muy alto para un 37%. La prevalencia de las dislipemias fue 84,3%, a predominio de hipercolesterolemia (33,7%) y dislipemia aterogénica (19,5%). El 60.6% (290) de los pacientes presenta indicación de tratamiento con estatinas, solo el 38.9%. (113) las recibe. El 38.1% (43) alcanzan los objetivos terapéuticos. Conclusiones : La obesidad presenta múltiples comorbilidades que aumentan el RCV, aun así se encuentra subestimada por las calculadoras de riesgo. Queda en evidencia un infratratamiento farmacológico de estos pacientes, no logrando los objetivos terapéuticos propuestos.

Introduction: Obesity is related to a high cardiovascular risk (CVR). This forces us to take therapeutic and preventive behaviors. The objective of this work is to evaluate cardiovascular risk in a morbidly obese population and assess the correct indication of statins. Methodology: Cross-sectional, descriptive, observational study, with the morbidly obese population of the Obesity and Bariatric Surgery Program (POCB) of the Maciel Hospital, from November 2014 to March 2020. CVR was assessed with the calculator of the Pan-American health organization. The indication for statins was considered according to CVR or diagnosis of dyslipidemia. Results: 478 patients were analyzed, 84.3% were women, the median age was 44 years, and the BMI was 50 kg/m2. A low CVR was calculated for 57% of patients; and high or very high for 37%. The prevalence of dyslipidemia was 84.3%, with a predominance of hypercholesterolemia (33.7%) and atherogenic dyslipidemia (19.5%). 60.6% (290) of patients have an indication for treatment with statins, only 38.9%. (113) receives them. 38.1% (43) achieved therapeutic objectives. Conclusions: Obesity presents multiple comorbidities that increase CVR, yet it is underestimated by risk calculators. Pharmacological undertreatment of these patients is evident, not achieving the proposed therapeutic objectives.

Introdução : A obesidade está relacionada a um alto risco cardiovascular (RCV). Isso nos obriga a adotar comportamentos terapêuticos e preventivos. O objetivo deste trabalho é avaliar o risco cardiovascular em uma população com obesidade mórbida e avaliar a correta indicação de estatinas. Metodologia: Estudo transversal, descritivo, observacional, com a população com obesidade mórbida do Programa de Obesidade e Cirurgia Bariátrica (POCB) do Hospital Maciel, no período de novembro de 2014 a março de 2020. O RCV foi avaliado com a calculadora da organização pan-americana de saúde. A indicação de estatinas foi considerada de acordo com RCV ou diagnóstico de dislipidemia. Resultados: Foram analisados ​​478 pacientes, 84,3% eram mulheres, a mediana de idade foi de 44 anos e o IMC foi de 50 kg/m2. Um RCV baixo foi calculado para 57% dos pacientes; e alto ou muito alto para 37%. A prevalência de dislipidemia foi de 84,3%, com predomínio de hipercolesterolemia (33,7%) e dislipidemia aterogênica (19,5%). 60,6% (290) dos pacientes têm indicação de tratamento com estatinas, apenas 38,9%. (113) os recebe. 38,1% (43) alcançaram objetivos terapêuticos. Conclusões: A obesidade apresenta múltiplas comorbidades que aumentam o RCV, mas é subestimada pelas calculadoras de risco. É evidente o subtratamento farmacológico destes pacientes, não atingindo os objetivos terapêuticos propostos.

Assessment of correlation between lipid ratios and body mass index in patients with type 2 diabetes mellitus in Sarajevo, Bosnia and Herzegovina.

Objective. Studies that have evaluated correlation between body mass index (BMI) and novel lipid indices such as triglycerides (TG)/high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC)/HDL-C, and low-density lipoprotein cholesterol (LDL-C)/HDL-C in type 2 diabetes mellitus (T2DM) are scarce. Hence, the aim of the present study was to explore the correlation between BMI and novel lipid indices in Bosnian patients with T2DM. Methods. Present study included 117 patients with T2DM (mean age: 66.51 years) and 68 controls (mean age: 68.37 years). BMI was calculated as weight/height². Lipids were measured by standard methods. TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were separately calculated. The differences between the groups were assessed by Student's t-test or Man Whitney U test. Correlations were determined by Spearman's test. Results. In a total sample of T2DM patients, 41.0% were overweight and 44.4% were obese. In the control group, 51.5% of subjects were overweight and 25.0% were obese. In T2DM group, a significant correlation was observed between BMI and HDL-C, LDL-C, TG/HDL, TC/HDL-C, and LDL-C/HDL-C ratios. In the control group, there was a significant correlation found between BMI and HDL-C, TG, TG/HDL, TC/HDL-C, and LDL-C/HDL-C-ratios. Correlation between BMI and other lipid parameters in T2DM and the control group was not determined. Conclusion. The present study showed significant correlation between BMI and novel lipid indices in both T2DM patients and the control group of subjects. Possible explanation for the observed results might be prevalence of overweight and obese participants in this study sample. Since novel lipid indices are used in the prediction of cardiometabolic risk, results obtained in the present study have valuable clinical implications.

Transitioning Adolescents and Young Adults with Lipid Disorders to Adult Health Care.

PURPOSE OF REVIEW: Pediatric healthcare providers have increasingly become aware of the need for timely and informative transition of adolescents and young adults with chronic medical conditions such as diabetes and cystic fibrosis. However, there is paucity of published data on the importance of and most effective way to transition youth with lipid disorders who are at increased risk of premature cardiovascular disease. RECENT FINDINGS: Evidence shows that atherosclerosis begins at a young age. However, there are no guidelines on the transition of adolescents and young adults with dyslipidemia. In addition, there are conflicting guidelines for lipid management in children versus adults, despite advances in medical pharmacotherapies for dyslipidemia. The lack of guidelines for transition and discordant recommendations for management of this vulnerable population places young adults at-risk for worsening of their underlying disease, and premature cardiovascular events.

Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition).

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.

ENaC gene variants and their involvement in Covid­19 severity.

Epidemiological studies report the association of diverse cardiovascular conditions with coronavirus disease 2019 (COVID-19), but the causality has remained to be established. Specific genetic factors and the extent to which they can explain variation in susceptibility or severity are largely elusive. The present study aimed to evaluate the link between 32 cardio-metabolic traits and COVID-19. A total of 60 participants were enrolled, who were categorized into the following 4 groups: A control group with no COVID-19 or any other underlying pathologies, a group of patients with a certain form of dyslipidemia and predisposition to atherosclerotic disease, a COVID-19 group with mild or no symptoms and a COVID-19 group with severe symptomatology hospitalized at the Intensive Care Unit of Sotiria Hospital (Athens, Greece). Demographic, clinical and laboratory data were recorded and genetic material was isolated, followed by simultaneous analysis of the genes related to dyslipidemia using a custom-made next-generation sequencing panel. In the COVID-19 group with mild or absent symptoms, the variant c.112C>T:p.P38S was detected in the sodium channel epithelial 1 subunit α (SCNN1A) gene, with a major allele frequency (Maf) of <0.01. In the COVID-19 group with severe symptoms, the variant c.786G>A:p.T262T was detected in the SCNN1B gene, which encodes for the ß-subunit of the epithelial sodium channel ENaC, with a Maf <0.01. None of the two rare variants were detected in the control or dyslipidemia groups. In conclusion, the current study suggests that ENaC variants are likely associated with genetic susceptibility to COVID-19, supporting the rationale for the risk and protective genetic factors for the morbidity and mortality of COVID-19.

Cognitive function in dyslipidemia patients: exploring the impact of statins.

Background: Evidence regarding the relationship between the use of statins and cognitive outcomes presents varying findings. This study aims to analyze the relationship between sustained statin use and cognitive performance in dyslipidemia patients. Methods: This study presents findings from the Beijing Ageing Brain Rejuvenation Initiative (BABRI) study, in which a cohort of community-dwelling dyslipidemia patients (Entire sample, N = 1,062, aged 50-86) was recruited. Participants were divided into two groups based on their sustained use statins (Statins group, N = 677) or not use any lipid-lowering agents (Untreated group, N = 385). Furthermore, the entire sample was stratified by age into the middle-aged sample (N = 451) and the older people sample (N = 611), following a similar categorization based on statin application. ANCOVA was used to evaluate the relationship between sustained statin use and cognitive function. Results: Overall, in the total sample, the statins group demonstrated better cognition in overall cognition, memory, visuospatial ability, attention, executive function, and language domains compared to the untreated group. Moreover, the statins group only showed better performance in attention among the middle-aged sample. In the older people sample, statins group exhibited superior cognitive performance across various cognitive domains compared to untreated group. Conclusion: Among dyslipidemia patients in Beijing community, sustained statin users exhibited superior cognitive function across all domains compared to untreated individuals, with particularly noticeable improvements among those aged 65 and above. These findings underscore the protective effect of statins on cognitive function in dyslipidemia patients, highlighting significant benefits for the older people population.

Eligibility for marine omega-3 fatty acid supplementation after acute coronary syndromes.

Background and aims: The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS). Methods: In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility. Results: Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged <70 (34 vs 25 %), smokers (38 vs 28 %), diabetics (46 vs 29 %), hypertensive (35 vs 29 %), and obese patients (46 vs 22 % for normal weight), all with p-values <0.001. Conclusion: In a contemporary Swiss cohort of patients with ACS, up to 32 % would be eligible for omega-3 FA-EPA supplementation one year after ACS, highlighting an opportunity to mitigate residual cardiovascular risk in patients with ACS and hypertriglyceridemia.

Potential causal and temporal relationship between plasma triglyceride levels and circulating leukocyte.

BACKGROUND: Circulating triglyceride (TG) and leukocytes, the main components of the vascular system, may impact each other and co-fuel atherosclerosis. While the causal relationship between plasma TG levels and leukocyte counts remains unclear. METHODS: Bidirectional mendelian randomisation (MR) analysis was conducted to investigate the potential causal relationship between TG levels and the counts of leukocytes and their subtypes. A cross-lagged panel model (CLPM) using a longitudinal healthy screening data (13,389 adults with an follow-up of 4 years) was fitted to examine the temporal relationship between them. RESULTS: Genetically predicted plasma TG levels were positively associated with total leukocyte counts (TLC) [ß(se)=0.195(0.01)], lymphocyte counts (LC) [ß(se)=0.196(0.019)], and neutrophill counts (NC) [ß(se)=0.086(0.01)], which remained significant after adjusting for several confounders. Inversely, the genetically predicted TLC [ß(se)=0.033(0.008)], LC [ß(se)=0.053(0.008)], and NC [ß(se)=0.034(0.008)] were positively associated with plasma TG levels. However, when all three of them were put into the MR model adjusted for each other, only LC was significantly associated with TG levels. There was no association between genetically predicted TG levels and monocyte counts (MC), basophil counts, and eosinophill counts. The results of CLPM showed that the temporal effect of elevated TLC, MC, LC, and NC on plasma TG levels were stronger than the inverse effect. CONCLUSION: Our findings suggesting a causal associations of plasma TG levels with TLC, LC, and NC. In turn, LC was positively associated with plasma TG levels. Additionally, elevated circulating LC may precede high plasma TG levels.

[Adult and pediatric thesaurismosis: Lysosomal, lipid and glycogen storage diseases]. / Thésaurismoses adultes et pédiatriques : maladies de surcharge lysosomale, surcharges lipidiques et glycogénoses.

Thesaurismosis or storage diseases are rare genetic disorders due to an abnormal accumulation of an organic compound or its metabolite within cells. These conditions are either secondary to a defect in catabolism caused by enzymatic dysfunction or to a deficiency in transport proteins. They encompass lysosomal storage diseases, lipid storage diseases or dyslipidemias, and glycogen storage disorders or glycogenoses. Diagnosis is typically based on clinical and biological anomalies but may be made or suggested by the pathologist when symptoms are atypical or when biochemical or genetic tests are challenging to interpret. For accurate diagnosis, it is crucial to freeze a portion of the samples. Special staining and electronic microscopy can also aid in the diagnostic process. As the diagnosis is multidisciplinary, collaboration with clinicians, biochemists and geneticists is essential.

The association between perceived neighborhood safety and cardiovascular disease risk factors.

Cardiovascular disease (CVD) remains the leading cause of mortality in the U.S. accounting for 1 in 4 deaths each year. Environmental factors, such as neighborhood safety, may increase the risk of CVD. Therefore, the current study assessed perceived neighborhood safety and its association with CVD risk factors (i.e. dyslipidemia, hypertension, type II diabetes) among 663 adults (mean age: 49.97 years, 61.24% female, 78.28% White). Participants completed self-report measures as part of a larger study of environmental influences on cardiac health. Results indicated that individuals reporting low perceived neighborhood safety had greater odds of having at least one CVD risk factor (OR = 2.76, 95% CI: 1.46, 5.22) compared to those with high perceived safety. There was a significant interaction between gender and the presence of at least one CVD risk factor in relation to perceived neighborhood safety. Low perceived neighborhood safety was associated with greater odds of having at least one CVD risk factor among males (OR = 5.48, 95% C.I: 1.82, 16.52) but not females. These findings suggest that low perceived safety is associated with CVD risk factors, especially among males. Future work should seek to better understand the interaction by gender in the relationship between perceived safety and CVD risk factors.

Akkermansia Muciniphila supplementation improves hyperlipidemia, cardiac function, and gut microbiota in high fat fed apolipoprotein E-deficient mice.

Hyperlipidemia, obesity and gut dysbiosis are pivotal risk factors for atherosclerotic cardiovascular disease (ACVD). Supplementation of Akkermansia muciniphila (AKK) has also been proven to be effective in the prevention and treatment of obesity and other metabolic disorders. Here we found that AKK was more abundant in healthy control than ACVD patients via metagenomic sequencing on fecal samples. Subsequently, we investigated the role and underlying mechanism of AKK on obesity-associated atherosclerosis. AKK intervention partially reversed the exacerbation of atherosclerotic lesion formation in ApoE-/- mice by improving dyslipidemia. Interestingly, replenishment with AKK significantly enhanced cardiac function and reduced the body weight. It also reduced pro-inflammatory cytokine IL-6 and increased anti-inflammatory IL-10 in the circulation. Additionally, AKK colonization dramatically regulated gut microbiota and increased the abundance of Lactobacillaceae. Our findings have provided novel insights into the therapeutic potential of AKK as a beneficial microbe for treating atherosclerotic-associated cardiovascular diseases.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients Following Acute Coronary Syndromes: From Lipid Lowering and Plaque Stabilization to Improved Outcomes.

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting.

Salvia elegans Vahl Counteracting Metabolic Syndrome and Depression in Mice on a High-Fat Diet.

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1ß, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS.

A Case-Based Approach to the Management of Patients with Chronic Coronary Disease: Updates from the 2023 AHA/ACC Guidelines.

The 2023 American Heart Association (AHA)/American College of Cardiology (ACC) Multisociety Guideline for the Management of Patients with Chronic Coronary Disease presents important updates to the care of patients with chronic coronary disease (1). The recommendations of these guidelines inform the care for patients with (1) asymptomatic coronary artery disease, (2) stable angina or equivalent symptoms (e.g., dyspnea upon exertion), (3) symptomatic nonobstructive coronary disease including coronary microvascular dysfunction and vasospasm, and (4) left ventricular (LV) systolic dysfunction with known coronary artery disease. In this review, we aim to demonstrate key recommendations in the 2023 guideline using the following four hypothetical cases.

Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for both mother and child. Effective management strategies are necessary, especially for pregnant women with inherited forms of dyslipidemia (i.e., familial hypertriglyceridemia, hyperchylomicronemia), where personalized dietary adjustments are crucial for successful pregnancy outcomes. Pharmacological interventions and lipoprotein apheresis may be necessary for severe cases, though their use is often limited by factors such as cost, availability, and potential fetal risks. Despite the promise of advanced therapies, their widespread application remains constrained by limited studies and high costs. Thus, a personalized, multidisciplinary approach is essential for optimizing outcomes. This review provides a comprehensive overview of current strategies and evidence-based practices for managing dyslipidemia during pregnancy, emphasizing the balance of maternal and fetal health. Additionally, it discusses the physiological changes in lipid metabolism during pregnancy and their implications, particularly for women with inherited forms of dyslipidemia.

Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial.

The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia.

Aerobic Exercise Training Protects Against Insulin Resistance, Despite Low-Sodium Diet-Induced Increased Inflammation and Visceral Adiposity.

Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.

Feeding Parenteral Nutrition in the Neonatal Period Programs Dyslipidemia in Adulthood in Yucatan Miniature Pigs.

BACKGROUND: Early nutritional challenges can lead to permanent metabolic changes, increasing risk of developing chronic diseases later in life. Total parenteral nutrition (TPN) is a life-saving nutrition regimen, used especially in intrauterine growth-restricted (IUGR) neonates. Early TPN feeding alters metabolism, but whether these alterations are permanent is unclear. Programmed metabolism is likely caused by epigenetic changes due to imbalances of methyl nutrients. OBJECTIVES: We sought to determine whether feeding TPN in early life would increase risk of developing dyslipidemia in adulthood and whether supplementing the methyl nutrients betaine and creatine to TPN would prevent this development. We also sought to determine whether IUGR exacerbates the effects of neonatal TPN on lipid metabolism in adulthood. METHODS: Female piglets (n = 32; 7 d old) were used in 4 treatments: 24 normal-weight piglets were randomly assigned to sow-fed (SowFed), standard TPN (TPN-control), and TPN with betaine and creatine (TPN-B+C); 8 IUGR piglets were fed control TPN (TPN-IUGR) as a fourth group. After 2 wk of treatment, all pigs were then fed a standard solid diet. At 8 mo old, central venous catheters were implanted to conduct postprandial fat tolerance tests. RESULTS: Feeding TPN in the neonatal period led to dyslipidemia in adulthood, as indicated by higher postprandial triglyceride (TG) levels in TPN-control (P < 0.05), compared with SowFed. IUGR piglets were particularly sensitive to neonatal TPN feeding, as TPN-IUGR piglets developed obesity and dyslipidemia in adulthood, as indicated by greater backfat thickness (P < 0.05), higher liver TG (P < 0.05), slower postprandial TG clearance (P < 0.05), and elevated fasting plasma nonhigh-density lipoprotein-cholesterol (P < 0.01), and nonesterified fatty acids (P < 0.001), compared with TPN-control. CONCLUSIONS: Feeding TPN in early life increases the risk of developing dyslipidemia in adulthood, especially in IUGR neonates; however, methyl nutrient supplementation to TPN did not prevent TPN-induced changes in lipid metabolism.

An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry.

Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (Rp > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.

Sleep and nighttime behavior disorders in older adults: associations with hypercholesterolemia and hypertriglyceridemia at baseline, and a predictive analysis of incident cases at 12 months follow-up.

INTRODUCTION: Sleep disorders, particularly insomnia and obstructive sleep apnea, are associated with dyslipidemia in the general population. The study's aim was to explore the association between pathological Cholesterol and Triglyceride levels, and sleep and nighttime behavior disorders (SNBD) in older adults, whether they might predict SNBD onset, and to emphasize the role of body mass index (BMI) in this association. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between hypercholesterolemia, hypertriglyceridemia, and SNBD at baseline and at 12 months. Relevant confounders, particularly BMI, were adjusted for. RESULTS: Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 years (IQR: 68, 78). At baseline, 357 (16%) had SNBD and 327 (18%) at 12 months; 187 of them were incident cases. There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, P-value = 0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, P-value = 0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, P-value < 0.001). Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR = 1.43, 95%CI: 1.13,1.80, P-value = 0.003), even after adjustment for confounding factors (adj. OR = 1.36, 95%CI: 1.06,1.74, P-value = 0.016) and (BMI-adj. OR = 1.29, 95%CI: 1.00,1.66, P-value = 0.048). None of the dyslipidemia forms did predict incident cases at 12 months. CONCLUSIONS: Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. The association was independent of BMI. None of the dyslipidemia forms did predict incident SNBD over 12 months. Sleep disorders should motivate a systematic screening of dyslipidemia in older adults and vice versa.