Improvement Science Increases Routine Lipid Screening in General Pediatric Cardiology.

OBJECTIVE: To evaluate the effectiveness of patient education, physician counseling, and point-of-care (POC) testing on improving adherence to lipid screening national guidelines in a general pediatric cardiology practice (2017-2023). STUDY DESIGN: Regional primary care providers were surveyed regarding lipid screening practices. Key drivers were categorized (physician, patient, and system) with corresponding interventions. Pediatric cardiologists started offering lipid screening during regular visits by providing families with preventive cardiovascular education materials and lab phlebotomy testing. System redesign included educational posters, clinical intake protocol, physician counseling, electronic health record integration, and POC testing. Run charts and statistical process control charts measured screening rates and key processes. RESULTS: The primary care survey response rate was 32% (95/294); 97% supported pediatric cardiologists conducting routine lipid screening. Pediatric cardiology mean baseline lipid screening rate was 0%, increased to 7% with patient education, and to 61% after system redesign including POC testing. Screening rates among 1467 patients were similar across age groups (P = .98). More patients received lipid screening by POC (91.7%) compared with phlebotomy (8.3%). Lipid abnormalities detected did not differ by screening methodology (P = .49). CONCLUSION: Patient education, counseling, and POC testing improved adherence to national lipid screening guidelines, providing a possible model for primary care implementation.

Targeting systemic inflammation in metabolic disorders. A therapeutic candidate for the prevention of cardiovascular diseases?

Cardiovascular disease (CVD) remains the leading cause of death and disability worldwide. While many factors can contribute to CVD, atherosclerosis is the cardinal underlying pathology, and its development is associated with several metabolic risk factors including dyslipidemia and obesity. Recent studies have definitively demonstrated a link between low-grade systemic inflammation and two relevant metabolic abnormalities: hypercholesterolemia and obesity. Interestingly, both metabolic disorders are also associated with endothelial dysfunction/activation, a proinflammatory and prothrombotic phenotype of the endothelium that involves leukocyte infiltration into the arterial wall, one of the earliest stages of atherogenesis. This article reviews the current literature on the intricate relationship between hypercholesterolemia and obesity and the associated systemic inflammation and endothelial dysfunction, and discusses the effectiveness of present, emerging and in-development pharmacological therapies used to treat these metabolic disorders with a focus on their effects on the associated systemic inflammatory state and cardiovascular risk.

Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care.

Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution.

Messenger RNA (mRNA) vaccines have demonstrated efficacy against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in humans. mRNA technology holds tremendous potential for rapid control and prevention of emergencies due to its flexibility with respect to production, application, and design for an efficacious and safe use in humans. We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full-length of the SARS-CoV-2 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid-1 in preclinical animal models. In the repeated dose toxicity study, rabbits received three intramuscular (IM) injections of MRT5500 at 3-week interval followed by a 4-week observation period. In an exploratory biodistribution study in mice receiving a single IM injection of an mRNA encoding luciferase encapsulated in an LNP containing Lipid-1, the expression of the luciferase protein was monitored in vivo and ex vivo at several time points. In the regulatory biodistribution study in rabbits receiving a single IM injection of MRT5500, the quantification of the mRNA and the ionizable Lipid-1 were monitored in the same organs and time points as in the exploratory biodistribution study. MRT5500 was safe and well-tolerated with a transient acute phase response/inflammation and an expected vaccine-related immunological response, typical of those observed following a vaccine administration. The biodistribution data demonstrated that the mRNA and Lipid-1 components of the vaccine formulations were mainly detected at the injection site and in the draining lymph nodes. These results support the use of MRT5500 and its deployment into clinical trials.

Development of Nanopackaging for Storage and Transport of Loaded Lipid Nanoparticles.

Easily deploying new vaccines globally to combat disease outbreaks has been highlighted as a major necessity by the World Health Organization. RNA-based vaccines using lipid nanoparticles (LNPs) as a drug delivery system were employed to great effect during the recent COVID-19 pandemic. However, LNPs are still unstable at room temperature and agglomerate over time during storage, rendering them ineffective for intracellular delivery. We demonstrate the suitability of nanohole arrays (nanopackaging) as patterned surfaces to separate and store functionalized LNPs (fLNPs) in individual recesses, which can be expanded to other therapeutics. Encapsulating calcein as a model drug, we show through confocal microscopy the effective loading of fLNPs into our nanopackaging for both wet and dry systems. We prove quantifiably pH-mediated capture and subsequent unloading of over 30% of the fLNPs using QCM-D on alumina surfaces altering the pH from 5.5 to 7, displaying controllable storage at the nanoscale.

Microalgae to biodiesel: A novel green conversion method for high-quality lipids recovery and in-situ transesterification to fatty acid methyl esters.

Greenhouse gases (GHGs) emissions due to increasing energy demand have raised the need to identify effective solutions to produce clean and renewable energy. Biotechnologies are an effective platform to attain green transition objectives, especially when synergically integrated to promote health and environmental protection. In this context, microalgae-based biotechnologies are considered among the most effective tools for treating gaseous effluents and simultaneously capturing carbon sources for further biomass valorisation. The production of biodiesel is regarded as a promising avenue for harnessing value from residual algal biomass. Nonetheless, the existing techniques for extracting lipids still face certain limitations, primarily centred around the cost-effectiveness of the process.This study is dedicated to developing and optimising an innovative and cost-efficient technique for extracting lipids from algal biomass produced during gaseous emissions treatment based on algal-bacterial biotechnology. This integrated treatment technology combines a bio-scrubber for degrading gaseous contaminants and a photobioreactor for capturing the produced CO2 within valuable algal biomass. The cultivated biomass is then processed with the process newly designed to extract lipids simultaneously transesterificated in fatty acid methyl esters (FAME) via In Situ Transesterification (IST) with a Kumagawa-type extractor. The results of this study demonstrated the potential application of the optimised method to overcome the gap to green transition. Energy production was obtained from residuals produced during the necessary treatment of gaseous emissions. Using hexane-methanol (v/v = 19:1) mixture in the presence KOH in Kumagawa extractor lipids were extracted with extraction yield higher than 12% and converted in fatty acid methyl esters. The process showed the enhanced extraction of lipids converted in bio-sourced fuels with circular economy approach, broadening the applicability of biotechnologies as sustainable tools for energy source diversification.

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma.

Astaxanthin is a valuable carotenoid and is used as antioxidant and health care. Phaffia rhodozyma is a potential strain for the biosynthesis of astaxanthin. The unclear metabolic characteristics of P. rhodozyma at different metabolic stages hinder astaxanthin's promotion. This study is conducted to investigate metabolite changes based on quadrupole time-of-flight mass spectrometry metabolomics method. The results showed that the downregulation of purine, pyrimidine, amino acid synthesis, and glycolytic pathways contributed to astaxanthin biosynthesis. Meanwhile, the upregulation of lipid metabolites contributed to astaxanthin accumulation. Therefore, the regulation strategies were proposed based on this. The addition of sodium orthovanadate inhibited the amino acid pathway to increase astaxanthin concentration by 19.2%. And the addition of melatonin promoted lipid metabolism to increase the astaxanthin concentration by 30.3%. It further confirmed that inhibition of amino acid metabolism and promotion of lipid metabolism were beneficial for astaxanthin biosynthesis of P. rhodozyma. It is helpful in understanding metabolic pathways affecting astaxanthin of P. rhodozyma and provides regulatory strategies for metabolism.

The Transformative Potential of Lipid Nanoparticle-Protein Corona for Next-Generation Vaccines and Therapeutics.

The integration of the lipid nanoparticle (LNP)-protein corona as a pioneering approach for the development of vaccines against the present and future SARS-CoV-2 variants of concern marks a significant shift in the field. This concept holds great promise, offering a universal platform that can be adaptable to combat future pandemics caused by unknown viruses. Understanding the complex interactions among the protein corona, LNPs, and receptors is crucial for harnessing its potential. This knowledge will allow optimal vaccine formulations and improve their effectiveness. Safety assessments are essential to ensure suitability for human use, compliance with regulatory standards, and rigorous quality control in manufacturing. This transformative workflow requires collaborative efforts, expanding our foundational knowledge and translating advancements from the laboratory to clinical reality. The LNP-protein corona approach represents a paradigmatic shift with far-reaching implications. Its principles and insights can be leveraged beyond specific applications against SARS-CoV-2, enabling a universal platform for addressing viral threats, cancer, and genetic diseases.

Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study.

BACKGROUND: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States. OBJECTIVE: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin. STUDY DESIGN: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models. RESULTS: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis. CONCLUSION: Here, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

Neonatal Intensive Care Unit Mixed Lipid Emulsion Use Associated With Reduced Cholestasis at Discharge in Surgical Patients.

INTRODUCTION: Parenteral nutrition associated cholestasis (PNAC) is a common morbidity in neonates requiring total parenteral nutrition (TPN). Previous studies in infants with intestinal failure have shown a benefit of mixed lipid emulsion (MLE) in reducing PNAC. It is not known whether this benefit extends to a general neonatal intensive care unit (NICU) population, where MLE is used on a selective basis. The objective of this study is to examine associations between MLE use and PNAC rate in the general NICU setting. METHODS: This is a retrospective review of NICU patients who received TPN for 7 or more days. We compared patients born between 1/1/2014 and 12/31/2015 (pre-MLE) to patients born between 7/1/2017 and 12/31/2018 (post-MLE). Fisher's exact test and two-sample t-test were used to compare the two groups. RESULTS: There were 353 patients in 2014-2015 and 271 patients in 2017-2018. Demographics were similar between the two groups, but there were more patients with congenital heart disease in the MLE era (P < 0.001). Mortality was similar (6.2% pre-MLE versus 6.3% post-MLE). There was no significant difference in PNAC rate between the pre-MLE (11.5%) and post-MLE (14.1%) patient cohorts (P = 0.342). Among patients receiving MLE (n = 38), 58% developed PNAC, while only 6.4% of the post-MLE cohort not receiving MLE developed PNAC. Of the patients coded with a surgical diagnosis, there was no significant difference in PNAC rates between pre-MLE and post-MLE groups. Discharge rates of PNAC did differ between pre-MLE surgical patients (13.0%) and post-MLE surgical patients (8.2%). In the subgroup of post-MLE surgical patients, PNAC rate differed significantly between those receiving MLE (43.5%) and not receiving MLE (15.4%). However, this difference was resolved by discharge (8.7% versus 7.7%). CONCLUSIONS: There were no significant differences in PNAC rates between the pre-MLE and post-MLE cohorts. However, in surgical patients, MLE was associated with reduced PNAC at discharge, with levels equivalent to those seen in neonates receiving TPN for 7 or more days, despite having a higher starting rate of PNAC. Further studies are needed to determine whether the general NICU population may benefit from MLE or certain selective subpopulations like surgical patients.

Lipid Microparticles Show Similar Efficacy With Lipid Nanoparticles in Delivering mRNA and Preventing Cancer.

PURPOSE: Messenger RNA (mRNA) has shown great promise for vaccine against both infectious diseases and cancer. However, mRNA is unstable and requires a delivery vehicle for efficient cellular uptake and degradation protection. So far, lipid nanoparticles (LNPs) represent the most advanced delivery platform for mRNA delivery. However, no published studies have compared lipid microparticles (LMPs) with lipid nanoparticles (LNPs) in delivering mRNA systematically, therefore, we compared the impact of particle size on delivery efficacy of mRNA vaccine and subsequent immune responses. METHODS: Herein, we prepared 3 different size lipid particles, from nano-sized to micro-sized, and they loaded similar amounts of mRNA. These lipid particles were investigated both in vitro and in vivo, followed by evaluating the impact of particle size on inducing cellular and humoral immune responses. RESULTS: In this study, all mRNA vaccines showed a robust immune response and lipid microparticles (LMPs) show similar efficacy with lipid nanoparticles (LNPs) in delivering mRNA and preventing cancer. In addition, immune adjuvants, either toll like receptors or active molecules from traditional Chinese medicine, can improve the efficacy of mRNA vaccines. CONCLUSIONS: Considering the efficiency of delivery and endocytosis, besides lipid nanoparticles with size smaller than 150 nm, lipid microparticles (LMPs) also have the potential to be an alternative and promising delivery system for mRNA vaccines.

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification.

OBJECTIVES: Attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. METHODS: A lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. RESULTS: Over the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. CONCLUSIONS: Delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.

Effectiveness of anthocyanins rich foods on cardiometabolic factors in individuals with metabolic syndrome: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review with meta-analysis was to determine whether anthocyanin-rich foods are effective to improve cardiometabolic markers in individuals with metabolic syndrome (MetS), compared with placebo or control interventions. METHODS: We searched MEDLINE, CENTRAL, Embase, LILACS, CINAHL, and Web of Science from their inception up to March 2022. We include clinical trials (randomized clinical trials, controlled clinical trials, and cross-over trials) with anthocyanin-rich foods versus placebo or control intervention that assessment cardiometabolic factors. RESULTS: We found 14 clinical trials that met the eligibility criteria, and we included 10 studies for the quantitative synthesis. For anthocyanin-rich foods versus control interventions, the mean difference (MD) for low-density lipoprotein (LDL) was - 7.98 mg/dL (CI = - 15.20 to - 0.77, GRADE: Very low). For homeostatic model assessment for insulin resistance (HOMA-IR), the MD was 0.04 (CI = 0.08 to 0.16, GRADE: Moderate). The MD for interleukin 6 was 0.00 pg/mL (CI = - 0.01 to 0.00, GRADE: Low). For tumor necrosis factor alpha (TNF-α), the standardized mean difference (SMD) was - 0.52 pg/mL (CI = 0.85 to 0.19 GRADE: Very low) when compared with the control interventions. The certainty of the evidence for the other outcomes it is very low. CONCLUSION: Our findings suggest that anthocyanin-rich foods could improve certain cardiometabolic markers (e.g., TC, TG, LDL, and TNF-α) among individuals with MetS (with very low quality evidence according to GRADE), compared with placebo or other control interventions. PROSPERO REGISTRATION NUMBER: CRD42020187287.

Clinical competence, communication ability and adherence to choosing wisely recommendations for lipid reducing drug use in older adults.

BACKGROUND: Although lipid-lowering drugs are not recommended for primary prevention in patients 75+, prevalence of use is high and there is unexplained variation in prescribing between physicians. The objective of this study was to determine if physician communication ability and clinical competence are associated with prescribing lipid-lowering drugs for primary and secondary prevention. METHODS: We used a cohort of 4,501 international medical graduates, 161,214 U.S. Medicare patients with hyperlipidemia (primary prevention) and 49,780 patients with a history of cardiovascular disease (secondary prevention) not treated with lipid-lowering therapy who were seen by study physicians in ambulatory care. Clinical competence and communication ability were measured by the ECFMG clinical assessment examination. Physician citizenship, age, gender, specialty and patient characteristics were also measured. The outcome was an incident prescription of lipid-lowering drug, evaluated using multivariable GEE logistic regression models for primary and secondary prevention for patients 75+ and 65-74. RESULTS: Patients 75+ were less likely than those 65-74 to receive lipid-lowering drugs for primary (OR 0.62, 95% CI 0.59-0.66) and secondary (OR 0.70, 95% CI 0.63-0.78) prevention. For every 20% increase in clinical competence score, the odds of prescribing therapy for primary prevention to patients 75+ increased by 24% (95% CI 1.02-1.5). Communication ability had the opposite effect, reducing the odds of prescribing for primary prevention by 11% per 20% score increase (95% CI 0.8-0.99) for both age groups. Physicians who were citizens of countries with higher proportions of Hispanic (South/Central America) or Asian (Asia/Oceania) people were more likely to prescribe treatment for primary prevention, and internal medicine specialists were more likely to treat for secondary prevention than primary care physicians. CONCLUSION: Clinical competence, communication ability and physician citizenship are associated with lipid-lowering drug prescribing for primary prevention in patients aged 75+.

To Boost or to Reset: The Role of Lactoferrin in Energy Metabolism.

Many pathological conditions, including obesity, diabetes, hypertension, heart disease, and cancer, are associated with abnormal metabolic states. The progressive loss of metabolic control is commonly characterized by insulin resistance, atherogenic dyslipidemia, inflammation, central obesity, and hypertension, a cluster of metabolic dysregulations usually referred to as the "metabolic syndrome". Recently, nutraceuticals have gained attention for the generalized perception that natural substances may be synonymous with health and balance, thus becoming favorable candidates for the adjuvant treatment of metabolic dysregulations. Among nutraceutical proteins, lactoferrin (Lf), an iron-binding glycoprotein of the innate immune system, has been widely recognized for its multifaceted activities and high tolerance. As this review shows, Lf can exert a dual role in human metabolism, either boosting or resetting it under physiological and pathological conditions, respectively. Lf consumption is safe and is associated with several benefits for human health, including the promotion of oral and gastrointestinal homeostasis, control of glucose and lipid metabolism, reduction of systemic inflammation, and regulation of iron absorption and balance. Overall, Lf can be recommended as a promising natural, completely non-toxic adjuvant for application as a long-term prophylaxis in the therapy for metabolic disorders, such as insulin resistance/type II diabetes and the metabolic syndrome.

Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis.

Controversy regarding the effects of betaine supplementation on cardiovascular markers has persisted for decades. This systematic review and meta-analysis compared the effects of betaine supplementation on cardiovascular disease (CVD) markers. Studies examining betaine supplementation on CVD markers published up to February 2021 were identified through PubMed, the Cochrane Library, Web of Science, Embase, and SCOPUS. Betaine supplementation had a significant effect on concentrations of betaine (MD: 82.14 µmol/L, 95% CI: 67.09 to 97.20), total cholesterol (TC) (MD: 14.12 mg/dl, 95% CI%: 9.23 to 19.02), low-density lipoprotein (LDL) (MD: 10.26 mg/dl, 95% CI: 6.14 to 14.38)], homocysteine (WMD: -1.30 micromol/L, 95% CI: -1.61 to -0.98), dimethylglycine (DMG) (MD: 21.33 micromol/L, 95% CI: 13.87 to 28.80), and methionine (MD: 2.06 micromol/L, 95% CI: 0.23 to 3.88). Moreover, our analysis indicated that betaine supplementation did not affect serum concentrations of triglyceride (TG), high-density lipoprotein (HDL), fasting blood glucose (FBG), C-reactive protein (CRP), liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)], and blood pressure. Our subgroup analysis suggested that a maximum dose of 4 g/d might have homocysteine-lowering effects without any adverse effect on lipid profiles reported with doses of ≥4 g/d. In conclusion, the present systematic review and meta-analysis supports the advantage of a lower dose of betaine supplementation (<4 g/d) on homocysteine concentrations without the lipid-augmenting effect observed with a higher dosage.

Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects.

OBJECTIVE: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). APPROACH AND RESULTS: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobinrelated proteins; P≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. CONCLUSIONS: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00715273; NCT00880178; NCT00120289.

On account of trans fatty acids and cardiovascular disease risk - There is still need to upgrade the knowledge and educate consumers.

AIMS: Trans fatty acids (TFAs) are unsaturated lipids either of industrial origin or naturally occurring in ruminant meat and milk. TFAs generated through food processing (industrial) is the main source in our diet and studies provide converging evidence on their negative effect on cardiovascular health. Since April 2021, the European Commission has put into effect a regulation for TFAs providing maximum 2% of total fat in all industrially produced foods. In light of this development, we review the evidence regarding the health attributes of different types of TFAs, their dietary sources and current intakes, and we describe the history of TFA-related legislative actions in an attempt to anticipate the efficiency of new measures. DATA SYNTHESIS: The PubMed database was searched including original research (observational and intervention studies), systematic reviews and meta-analyses. Scientific reports of competent authorities and organizations have also been screened. CONCLUSIONS: Trans-fat elimination provides a fine example of how evidence has led to the application of horizontal regulatory measures regarding legal food ingredients in order to protect consumers' health. In EU Member States, TFAs currently provide on average less than 1% of energy (1%E) and intakes marginally exceed recommendations primarily among young adults. Large dietary surveys however provide evidence for additional, less-well known sources of TFAs in the diet. Raising public awareness of "hidden" trans-fat found naturally in foods such as cheese, as well as of the trans-fat generated through traditional cooking practices is needed, if the goal to eliminate trans-fat from the diet is to be met.

Novel Adipose Tissue Targets to Prevent and Treat Atherosclerosis.

Adipose tissue as a major organ of lipid and lipoprotein metabolism has a major impact on metabolic homeostasis and thus influences the development of atherosclerosis and related cardiometabolic diseases. Unhealthy adipose tissue, which is often associated with obesity and systemic insulin resistance, promotes the development of diabetic dyslipidemia and can negatively affect vascular tissue homeostasis by secreting pro-inflammatory peptides and lipids. Conversely, paracrine and endocrine factors that are released from healthy adipose tissue can preserve metabolic balance and a functional vasculature. In this chapter, we describe adipose tissue types relevant for atherosclerosis and address the question how lipid metabolism as well as regulatory molecules produced in these fat depots can be targeted to counteract atherogenic processes in the vessel wall and improve plasma lipids. We discuss the role of adipose tissues in the action of approved drugs with anti-atherogenic activity. In addition, we present potential novel targets and therapeutic approaches aimed at increasing lipoprotein disposal in adipose tissue, boosting the activity of heat-producing (thermogenic) adipocytes, reducing adipose tissue inflammation, and improving or replacing beneficial hormones released from adipose tissues. Furthermore, we describe the future potential of innovative drug delivery technologies.

Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation.

The development of safe and effective vaccine formulations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a hallmark in the history of vaccines. Here we report a COVID-19 subunit vaccine based on a SARS-CoV-2 Spike protein receptor binding domain (RBD) incorporated into nano-multilamellar vesicles (NMV) associated with monophosphoryl lipid A (MPLA). The results based on immunization of C57BL/6 mice demonstrated that recombinant antigen incorporation into NMVs improved antibody and T-cell responses without inducing toxic effects under both in vitro and in vivo conditions. Administration of RBD-NMV-MPLA formulations modulated antigen avidity and IgG subclass responses, whereas MPLA incorporation improved the activation of CD4+/CD8+ T-cell responses. In addition, immunization with the complete vaccine formulation reduced the number of doses required to achieve enhanced serum virus-neutralizing antibody titers. Overall, this study highlights NMV/MPLA technology, displaying the performance improvement of subunit vaccines against SARS-CoV-2, as well as other infectious diseases.