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Lipoprotein lipase (LPL) and multiple regulators of LPL activity (e.g., APOC2 and ANGPTL4) are present in all vertebrates, but GPIHBP1-the endothelial cell (EC) protein that captures LPL within the subendothelial spaces and transports it to its site of action in the capillary lumen-is present in mammals but in not chickens or other lower vertebrates. In mammals, GPIHBP1 deficiency causes severe hypertriglyceridemia, but chickens maintain low triglyceride levels despite the absence of GPIHBP1. To understand intravascular lipolysis in lower vertebrates, we examined LPL expression in mouse and chicken hearts. In both species, LPL was abundant on capillaries, but the distribution of Lpl transcripts was strikingly different. In mouse hearts, Lpl transcripts were extremely abundant in cardiomyocytes but were barely detectable in capillary ECs. In chicken hearts, Lpl transcripts were absent in cardiomyocytes but abundant in capillary ECs. In zebrafish hearts, lpl transcripts were also in capillary ECs but not cardiomyocytes. In both mouse and chicken hearts, LPL was present, as judged by immunogold electron microscopy, in the glycocalyx of capillary ECs. Thus, mammals produce LPL in cardiomyocytes and rely on GPIHBP1 to transport the LPL into capillaries, whereas lower vertebrates produce LPL directly in capillary ECs, rendering an LPL transporter unnecessary.

We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.

The availability of pharmacological approaches able to effectively reduce circulating LDL cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease (CVD). However, a residual cardiovascular (CV) risk persists in treated individuals with optimal levels of LDL-C. Additional risk factors beyond LDL-C are involved, and among these, elevated levels of triglycerides (TGs) and TG-rich lipoproteins are causally associated with an increased CV risk. Apolipoprotein C-III (apoC-III) is a key regulator of TG metabolism and hence circulating levels through several mechanisms including the inhibition of lipoprotein lipase activity and alterations in the affinity of apoC-III-containing lipoproteins for both the hepatic receptors involved in their removal and extracellular matrix in the arterial wall. Genetic studies have clarified the role of apoC-III in humans, establishing a causal link with CVD and showing that loss-of-function mutations in the APOC3 gene are associated with reduced TG levels and reduced risk of coronary heart disease. Currently available hypolipidaemic drugs can reduce TG levels, although to a limited extent. Substantial reductions in TG levels can be obtained with new drugs that target specifically apoC-III; these include two antisense oligonucleotides, one small interfering RNA and an antibody.

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (

Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders.

Members of the Bacteroidota compose a large portion of the human gut microbiota, contributing to overall gut health via the degradation of various polysaccharides. This process is facilitated by lipoproteins, globular proteins anchored to the cell surface by a lipidated N-terminal cysteine. Despite their importance, lipoprotein synthesis by these bacteria is understudied. In Escherichia coli, the a-amino- linked lipid of lipoproteins is added by the lipoprotein N-acyltransferase Lnt. Herein, we have identified a protein distinct from Lnt responsible for the same process in Bacteroides, named lipoprotein N-acyltransferase in Bacteroides (Lnb). Deletion of Lnb yields cells that synthesize diacylated lipoproteins, with impacts on cell viability and morphology, growth on polysaccharides, and protein composition of membranes and outer membrane vesicles (OMVs). Our results not only challenge the accepted paradigms of lipoprotein biosynthesis in gram-negative bacteria but also suggest the existence of a new family of lipoprotein N-acyltransferases. [ABSTRACT FROM AUTHOR]

Currently available antiproprotein convertase subtilisin/kexin type 9 monoclonal antibodies can effectively decrease low-density lipoprotein cholesterol (LDL-C) levels, but require frequent dosing. Recaticimab is a novel humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. In a phase 1b/2 trial, recaticimab as add-on to stable statins showed robust LDL-C reduction with a dosing interval up to every 12 weeks (Q12W) in patients with hypercholesterolemia. REMAIN-2 (REcaticiMab Add-on therapy In patients with Nonfamilial hypercholesterolemia) aimed to assess the efficacy and safety of 48-week treatment with recaticimab as add-on therapy to statins in nonfamilial hypercholesterolemia. REMAIN-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. During the run-in period, patients received stable moderate or high-intensity statin, with or without cholesterol absorption inhibitors (ezetimibe) or fenofibrate, for ≥4 weeks. Patients with an LDL-C of ≥1.8 mmol/L (if with atherosclerotic cardiovascular disease [ASCVD]) or ≥2.6 mmol/L (if without ASCVD) were then randomized (2:2:2:1:1:1) to receive recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg Q12W, or matching placebo injections (Q4W, Q8W, or Q12W) for 48 weeks. The primary efficacy endpoint was percentage change from baseline to week 24 in LDL-C level. A total of 689 randomly assigned patients received treatment (mean age, 55.8 years; male, 64.4%; ASCVD history, 69.5%; concomitant ezetimibe, 11.2%; mean baseline LDL-C, 2.8 mmol/L). Percentage change in LDL-C from baseline to week 24 was significantly more pronounced with recaticimab vs placebo (P < 0.0001), with least-squares mean differences of −62.2% (95% CI: −67.0% to −57.4%), −59.7% (95% CI: −65.0% to −54.4%), and −53.4% (95% CI: −58.7% to −48.2%) for the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W regimens, respectively. The decreases in LDL-C with recaticimab were maintained through week 48. Secondary lipid variables, including non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) also favored the recaticimab groups. During the treatment period, the incidence of treatment-related adverse events (28.5% vs 26.6%) and serious treatment-related adverse events (0.4% vs 0.4%) was similarly low in both the recaticimab and placebo groups. Recaticimab as add-on to stable statin therapy significantly decreased LDL-C levels at week 24 and sustained the decreases through week 48, providing a novel therapeutic alternative with a dosing interval of up to every 12 weeks in patients with nonfamilial hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Identifying biomarkers for Alzheimer's disease (AD) is crucial, due to its complex pathology, which involves dysfunction in lipid transport, contributing to neuroinflammation, synaptic loss, and impaired amyloid-β clearance. Nuclear magnetic resonance (NMR) is able to quantify and stratify lipoproteins. The study investigated lipoproteins in blood from AD patients, aiming to evaluate their diagnostic potential. Serum and plasma were collected from AD patients (n = 25) and healthy individuals (n = 25). We conducted a comprehensive lipoprotein profiling on serum samples using NMR spectroscopy, analysing 112 lipoprotein subfractions. In plasma, we measured unspecific markers of neuronal damage and AD hallmark proteins using single molecule array technology. Additionally, clinical data and cerebrospinal fluid biomarker levels were also collected to enrich our data. Our findings, after adjusting for age and sex differences, highlight significant alterations in two specific lipoproteins; high-density lipoprotein (HDL)-1 Apo-A2 (H1A2) and HDL-2 Apo-A2 (H2A2), both with area under the curve (AUC) values of 0.67, 95% confidence interval (CI) = 0.52–0.82). These results indicate that these lipoprotein subfractions may have potential as indicators of AD-related metabolic changes. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction‐associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro‐inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid‐lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro‐inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre‐β‐HDL—the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA‐induced change in pro‐inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large‐scale study. [ABSTRACT FROM AUTHOR]

Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals. [ABSTRACT FROM AUTHOR]

ObjectiveMethodResultsConclusionInverse associations between systemic inflammation and cholesterol (‘the lipid paradox’) have been reported in rheumatoid arthritis (RA) and, in established axial spondyloarthritis (axSpA), but little is known about this relationship in early axSpA, which is the focus of the present study.In the Swedish part of the SPondyloArthritis Caught Early (SPACE) cohort (patients with chronic back pain for ≥3 months, ≤2 years; age at onset <45 years), serum levels of total cholesterol (TC) and apolipoproteins ApoA1 and ApoB were measured at inclusion, together with parameters reflecting inflammatory disease activity [C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and sacroiliitis by magnetic resonance imaging (MRI) following Assessment of SpondyloArthritis international Society (ASAS) criteria]. All patients included in the analysis either had axSpA based on a high physician’s level of confidence or fulfilled the ASAS criteria for axSpA. Associations between lipids/lipoproteins and inflammation were assessed using multivariable linear regression models.In the 64 patients included, there were inverse associations for CRP with TC, ApoA1, and ApoB in age–sex-adjusted models. The negative associations with CRP remained significant for TC and ApoB in multivariable models adjusted for age, sex, BASDAI, and current smoking (p = 0.048). There were no significant associations for the lipid parameters with BASDAI or inflammation on MRI of the sacroiliac joints.Inverse associations between systemic inflammation and lipids, particularly TC and ApoB, are present in early axSpA, similar to those shown for other inflammatory joint diseases. These patterns must be considered when including lipids in the evaluation of cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are mediators of intercellular communication, recently recognised for their clinical applications. Accurate characterisation and quantification of EVs are critical for understanding of their function and clinical relevance. Many platforms utilise fluorescence for EV characterisation, frequently labelling surface proteins to identify EVs. The heterogeneity of EVs and the lack of a universal protein marker encourages the use of generic EV labelling methods, including membrane labelling. Using nano‐flow cytometry, we evaluated six membrane dyes, including MemGlow and CellMask. Evaluation criteria included EV labelling efficacy, non‐specific labelling of very low‐density lipoproteins (VLDLs), brightness and dye aggregation. Significant variation was observed in dye performance, with certain dyes showing poor EV labelling efficacy or high affinity to VLDLs. Importantly, several promising candidates were identified for further investigation. Overall, this study highlights the importance of selecting appropriate membrane dyes for EV staining tailored to the aims of the study and the EV origin. MemGlow and CellMask proved favourable, allowing bright, sensitive staining of EV membranes with minimal aggregation. However, MemGlow showed an affinity to VLDLs, and CellMask requires additional sample handling for optimal labelling. These results contribute to deepening our understanding of EV membrane dyes, allowing for better dye selection and EV identification in future studies. [ABSTRACT FROM AUTHOR]

Background: Evidence-based screening is crucial to detect myocardial ischemia in high-risk diabetics. We explored the relationship between nitric oxide (NO) levels, lipid profile indices, and atherogenic index of plasma (AIP) in type 2 diabetics with coronary artery disease (CAD) and to determine their potential as prognostic markers. Materials and Methods: A case--control study included 50 diabetics with CAD (cases), 30 diabetics without CAD (control 1), and 23 healthy controls (control 2). Biochemical parameters were determined using standard protocols; plasma NO was measured via the Griess reaction. Results: Cases had the highest levels of NO, fasting blood sugar, glycated hemoglobin (HbA1c), and triglycerides, and the lowest total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Cases exhibited the highest TC: HDL-C, LDL-C: HDL-C, and AIP ratios. A significant positive correlation between NO and HbA1c (r = 0.328, P = 0.020). Conclusion: Chronic hyperglycemia could enhance NO overproduction driven by inducible isoform, suggesting a potential role for chronic hyperglycemia in endothelial dysfunction and vascular complications in diabetes. [ABSTRACT FROM AUTHOR]

Background:: Liver plays a vital role in lipid metabolism. It contributes both in exogenous and endogenous cycles of lipid metabolism and transport of lipids through plasma. Liver disease impacts on hepatic synthesis of lipoproteins and lipogenesis but data on dyslipidemia during disease progression are limited. Aims & Objectives: To assess the serum Lipid profile in patients diagnosed with chronic alcoholic liver disease (ALD) in a tertiary care level hospital and to assess the association of Serum Lipid profile alterations with the severity of alcoholic liver disease. Materials & Methods: The present study was conducted in the Department of Medicine, Dr Panjabrao Alias Bhausaheb Deshmukh Memorial Medical College and Research Centre, Amravati on 73 patients with chronic alcoholic liver disease and >18 years of age of both sex. Then they were subjected to Clinical data, including demographic information, medical history, liver function tests, imaging findings. Serum Lipid Profile Levels including triglycerides, cholesterol, and lipoproteins were measured using standardized laboratory assays, with values expressed in mg/dL. Disease severity was assessed using established scoring systems such as Child-Pugh classification. Results: Mean S Cholesterol levels was 192±43.67 mg/dl,S triglyceride was 136.9±87.23 mg/dl,HDL was 31.4±11.76 mg/dl,LDL was 92.58±32.64 mg/dl and VLDL was 27.54±14.12 mg/dl. One way Anova was applied which states that the S Cholesterol, Triglyceride and HDL had statistical significant difference among 3 groups with p value <0.05. Conclusion: The severity of Chronic alcoholic Liver Disease increases from Child pugh score class A to Child pugh score class C, the lipid panel profile decreases exponentially. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality. [ABSTRACT FROM AUTHOR]

Objectives Cardiovascular disease through accelerated atherosclerosis is a leading cause of mortality for patients with systemic lupus erythematosus (SLE), likely due to increased chronic inflammation and cardiometabolic defects over age. We investigated age-associated changes in metabolomic profiles of SLE patients and healthy controls (HCs). Methods Serum NMR metabolomic profiles from female SLE patients (n  = 164, age = 14–76) and HCs (n  = 123, age = 13–72) were assessed across age by linear regression and by age group between patients/HCs (Group 1, age ≤ 25, n  = 62/46; Group 2, age = 26–49, n  = 50/46; Group 3, age ≥ 50, n  = 52/31) using multiple t tests. The impact of inflammation, disease activity and treatments were assessed, and UK Biobank disease-wide association analysis of metabolites was performed. Results Age-specific metabolomic profiles were identified in SLE patients vs HCs, including reduced amino acids (Group 1), increased very-low-density lipoproteins (Group 2), and increased low-density lipoproteins (Group 3). Twenty-five metabolites were significantly altered in all SLE age groups, dominated by decreased atheroprotective high-density lipoprotein (HDL) subsets, HDL-bound apolipoprotein (Apo)A1 and increased glycoprotein acetyls (GlycA). Furthermore, ApoA1 and GlycA were differentially associated with disease activity and serological measures, as well as atherosclerosis incidence and myocardial infarction mortality risk through disease-wide association. Separately, glycolysis pathway metabolites (acetone/citrate/creatinine/glycerol/lactate/pyruvate) uniquely increased with age in SLE, significantly influenced by prednisolone (increased pyruvate/lactate) and hydroxychloroquine (decreased citrate/creatinine) treatment and associated with type 1 and type 2 diabetes by disease-wide association. Conclusions Increasing HDL (ApoA1) levels through therapeutic/nutritional intervention, whilst maintaining low disease activity, in SLE patients from a young age could improve cardiometabolic disease outcomes. Biomarkers from the glycolytic pathway could indicate adverse metabolic effects of current therapies. [ABSTRACT FROM AUTHOR]

Dyslipidemia is an important risk factor for cardiovascular morbidity and mortality. Although low-density lipoprotein (LDL) is primarily responsible, the importance of triglyceride (TG) and high-density lipoprotein (HDL) has also been recognized. The present study investigated the effect of the atherogenic index of plasma (AIP), in which atherogenic and protective lipoproteins were evaluated together, on the initial flow in patients with ST elevation myocardial infarction. AIP was calculated as log(TG/HDL-cholesterol). Patients included in the study (n = 1535) were divided into Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and >0. AIP was found to be significantly different between 2 groups (.55 ±.23 vs.67 ±.21; P <.001). AIP was an independent predictor for pre-intervention TIMI flow (Odds Ratio: 2.778). A moderate correlation was found between TIMI frame count measurements, calculated in patients with TIMI 2–3, and AIP (Pearson correlation coefficient:.63, P <.001). In the receiver operating characteristic analysis, AIP showed the highest area under curve (AUC) compared with other lipid parameters for predicting vascular patency. The AUC of AIP was.634, the cut-off value was.59, and the sensitivity and specificity were 67.6% and 68.4%, respectively (P <.001). In conclusion, AIP was found to be an important marker affecting pre-percutaneous coronary intervention TIMI flow. [ABSTRACT FROM AUTHOR]

Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization. The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non–high-density lipoprotein cholesterol (non–HDL-C) with CHD. Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C. Mendelian randomization analysis was used to estimate for each SNP cluster CHD ORs per 10 mg/dL apolipoprotein B (apoB) and per 0.33 mmol/L non–HDL-cholesterol, and to evaluate association of TRL/remnants with biomarkers of systemic inflammation. SNPs in cluster 1 predominantly affected LDL-C, whereas SNPs in cluster 10 predominantly affected TRL/remnant-C. CHD risk per genetically predicted increase in apoB and in non–HDL-C rose across clusters. ORs per 10 mg/dL higher apoB was 1.15 (95% CI: 1.11-1.19) in cluster 1 vs 1.70 (95% CI: 1.52-1.90) in cluster 10. Comparing ORs between these TRL/remnant-predominant and LDL-predominant clusters, we estimated that TRL/remnants were at least 3.9 (95% CI: 2.8-5.4) times more atherogenic than LDL on a per-particle basis. For non–HDL-C, CHD ORs per 0.33 mmol/L rose from 1.15 (95% CI: 1.11-1.19) for cluster 1 to 1.40 (95% CI: 1.30-1.50) for cluster 10. TRL/remnants exhibited causal relationships with inflammation, but this did not explain their greater atherogenicity. TRL/remnants are about 4 times more atherogenic than LDL. Variation in the causal association of non–HDL-C with CHD indicates that adjustment for percentage TRL/remnant-C may be needed for accurate risk prediction. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG. Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk. [ABSTRACT FROM AUTHOR]

Background: Retention of apolipoprotein B (apoB)-containing lipoproteins within the arterial wall plays a major causal role in atherosclerotic cardiovascular disease (ASCVD). There is a single apoB molecule in all apoB-containing lipoproteins. Therefore, quantitation of apoB directly estimates the number of atherogenic particles in plasma. ApoB is the preferred measurement to refine the estimate of ASCVD risk. Low-density lipoprotein (LDL) particles are by far the most abundant apoB-containing particles. In patients with elevated lipoprotein(a) (Lp(a)), apoB may considerably underestimate risk because Mendelian randomization studies have shown that the atherogenicity of Lp(a) is approximately 7-fold greater than that of LDL on a per apoB particle basis. In subjects with increased Lp(a), the association between LDL-cholesterol and incident CHD (coronary heart disease) is increased, but the association between apoB and incident CHD is diminished or even lost. Thus, there is a need to understand the mechanisms of Lp(a), LDL-cholesterol and apoB-related CHD risk and to provide clinicians with a simple practical tool to address these complex and variable relationships. How can we understand a patient's overall lipid-driven atherogenic risk? What proportion of this risk does apoB capture? What proportion of this risk do Lp(a) particles carry? To answer these questions, we created a novel metric of atherogenic risk: risk-weighted apolipoprotein B. Methods: In nmol/L: Risk-weighted apoB = apoB - Lp(a) + Lp(a) x 7 = apoB + Lp(a) x 6. Proportion of risk captured by apoB = apoB divided by risk-weighted apoB. Proportion of risk carried by Lp(a) = Lp(a) × 7 divided by risk-weighted apoB. Results: Risk-weighted apoB agrees with risk estimation from large epidemiological studies and from several Mendelian randomization studies. Conclusions: ApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB. [ABSTRACT FROM AUTHOR]

The Sonic hedgehog (Shh) signaling pathway controls embryonic development and tissue homeostasis after birth. This requires regulated solubilization of dual-lipidated, firmly plasma membrane-associated Shh precursors from producing cells. Although it is firmly established that the resistance-nodulation-division transporter Dispatched (Disp) drives this process, it is less clear how lipidated Shh solubilization from the plasma membrane is achieved. We have previously shown that Disp promotes proteolytic solubilization of Shh from its lipidated terminal peptide anchors. This process, termed shedding, converts tightly membrane-associated hydrophobic Shh precursors into delipidated soluble proteins. We show here that Disp-mediated Shh shedding is modulated by a serum factor that we identify as high-density lipoprotein (HDL). In addition to serving as a soluble sink for free membrane cholesterol, HDLs also accept the cholesterol-modified Shh peptide from Disp. The cholesteroylated Shh peptide is necessary and sufficient for Disp-mediated transfer because artificially cholesteroylated mCherry associates with HDL in a Disp-dependent manner, whereas an N-palmitoylated Shh variant lacking C-cholesterol does not. Disp-mediated Shh transfer to HDL is completed by proteolytic processing of the palmitoylated N-terminal membrane anchor. In contrast to dual-processed soluble Shh with moderate bioactivity, HDL-associated N-processed Shh is highly bioactive. We propose that the purpose of generating different soluble forms of Shh from the dual-lipidated precursor is to tune cellular responses in a tissue-type and time-specific manner. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary surfactant prevents alveolar collapse by reducing surface tension at the air–liquid interface. It contains two hydrophilic lectins, called SP-A and SP-D. They are factors of innate immune defence but also contribute to the surfactant structure and homeostasis. SP-A and SP-D recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs), which enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. The term "cancer" includes a variety of diseases, often incurable, difficult to diagnose and fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy. Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRMs), able to recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at the N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at the C-terminus). Pulmonary surfactant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air–liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeostasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term "cancer" includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes have increased risks for dyslipidaemia and subsequently for developing vascular complications. A recent meta-analysis found that cetoleic acid (C22:1n-11) rich fish oils resulted in lower cholesterol concentration in rodents. The aim was to investigate the effect of consuming fish oils with or without cetoleic acid on serum cholesterol concentration in diabetic rats and to elucidate any effects on cholesterol metabolism. Eighteen male Zucker Diabetic Sprague Dawley rats were fed diets containing herring oil (HERO) or anchovy oil (ANCO) or a control diet with soyabean oil for 5 weeks. The HERO diet contained 0·70 % cetoleic acid, with no cetoleic acid in the ANCO diet. The HERO and ANCO diets contained 0·35 and 0·37 wt% EPA + DHA, respectively. Data were analysed using one-way ANOVA. The serum total cholesterol concentration was 14 % lower in the HERO group compared with ANCO and Control groups (P = 0·023). The HERO group had a higher faecal excretion of bile acids (P = 0·0036), but the cholesterol production in the liver, the hepatic secretion of VLDL and the liver's capacity to take up cholesterol were similar to controls. The ANCO diet did not affect the serum cholesterol concentration, but the hepatic cholesterol biosynthesis, the clearance of lipoprotein cholesterol and the excretion of bile acids in faeces were higher than in the Control group. To conclude, consumption of herring oil, but not of anchovy oil, led to a lower cholesterol concentration in a type 2 diabetes rat model. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile. Methods: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L. Results: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07–3.06) mmol/L and 22 (IQR: 7.8–68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a). Conclusions: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol. [ABSTRACT FROM AUTHOR]

Background: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. Methods: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. Results: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. Conclusion: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications. [ABSTRACT FROM AUTHOR]

High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named "apo" lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders. [ABSTRACT FROM AUTHOR]

Over 50% of patients who take statins are still at risk of developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual risk is largely dependent on triglyceride-rich lipoproteins (TRL) and their remnants. In essence, remnant cholesterol-rich chylomicron (CM) and very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipoprotein lipase (LPL) activity is inhibited. ApoCIII has been thoroughly studied as a chief inhibitor and therapeutic options to curb its effect are available. On top of apoCIII regulation of LPL activity, there is a more precise control of LPL in various tissues, which makes it easier to physiologically divide the TRL burden according to the body's requirements. In general, oxidative tissues such as skeletal and cardiac muscle preferentially take up lipids during fasting. Conversely, LPL activity in adipocytes increases significantly after feeding, while its activity in oxidative tissues decreases concurrently. This perspective addresses the recent improvements in our understanding of circadian LPL regulations and their therapeutic implications. Three major tissue-specific lipolysis regulators have been identified: ANGPTL3, ANGPTL4, and ANGPTL8. Briefly, during the postprandial phase, liver ANGPTL8 acts on ANGPTL3 (which is released continuously from the liver) to inhibit LPL in the heart and muscle through an endocrine mechanism. On the other hand, when fasting, ANGPTL4, which is released by adipocytes, inhibits lipoprotein lipase in adipose tissue in a paracrine manner. ANGPTL3 inhibitors may play a therapeutic role in the treatment of hypertriglyceridemia. Several approaches are under development. We look forward to future studies to clarify (a) the nature of hormonal and nutritional factors that determine ANGPTL3, 4, and 8 activities, along with what long-term impacts may be expected if their regulation is impaired pharmacologically; (b) the understanding of the quantitative hierarchy and interaction of the regulatory actions of apoCIII, apoAV, and ANGPTL on LPL activity; (c) strategies for the safe and proper treatment of postprandial lipemia; and (d) the effect of fructose restriction on ANGPTL3, ANGPTL4, and ANGPTL8. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have successfully entered the clinic for the delivery of mRNA- and siRNA-based therapeutics, most recently as vaccines for COVID-19. Nevertheless, there is a lack of understanding regarding their in vivo behavior, in particular cell targeting. Part of this LNP tropism is based on the adherence of endogenous protein to the particle surface. This protein forms a so-called corona that can change, amongst other things, the circulation time, biodistribution and cellular uptake of these particles. The formation of this protein corona, in turn, is dependent on the nanoparticle properties (e.g., size, charge, surface chemistry and hydrophobicity) as well as the biological environment from which it is derived. With the potential of gene therapy to target virtually any disease, administration sites other than intravenous route are considered, resulting in tissue specific protein coronas. For neurological diseases, intracranial administration of LNPs results in a cerebral spinal fluid derived protein corona, possibly changing the properties of the lipid nanoparticle compared to intravenous administration. Here, the differences between plasma and CSF derived protein coronas on a clinically relevant LNP formulation were studied in vitro. Protein analysis showed that LNPs incubated in human CSF (C-LNPs) developed a protein corona composition that differed from that of LNPs incubated in plasma (P-LNPs). Lipoproteins as a whole, but in particular apolipoprotein E, represented a higher percentage of the total protein corona on C-LNPs than on P-LNPs. This resulted in improved cellular uptake of C-LNPs compared to P-LNPs, regardless of cell origin. Importantly, the higher LNP uptake did not directly translate into more efficient cargo delivery, underlining that further assessment of such mechanisms is necessary. These findings show that biofluid specific protein coronas alter LNP functionality, suggesting that the site of administration could affect LNP efficacy in vivo and needs to be considered during the development of the formulation. Schematic representation of the protein corona formation, isolation and characterization protocol. [Display omitted] • Unique protein coronas develop on the surface of lipid nanoparticles after exposure to human plasma or cerebrospinal fluid. • Biofluid specific protein coronas affect lipid nanoparticle performance and influence their uptake by cells in vitro in time. • Biofluid specific protein coronas affect lipid nanoparticle delivery efficiency of cargo siRNA to cells in vitro. • Lipid nanoparticle uptake is not a predictor for siRNA transfection efficiency in vitro • Difference in Apolipoprotein content in cerebrospinal fluid and plasma could affect lipid nanoparticle performance in vitro. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD. [ABSTRACT FROM AUTHOR]

Hypertension (HT) is a common chronic disease that often causes target-organ damage and severe complications, contributing to cardiovascular morbidity and mortality worldwide. Accumulating evidence suggests that inflammation plays a prominent role in the initiation and progression of HT. Multiple inflammatory biomarkers have been proposed to predict HT. Several new hematological parameters can reflect the inflammatory response and platelet activation. The major advantage of hematological parameters over conventional inflammatory markers is that they are relatively inexpensive and easily obtained from routine blood tests. Numerous studies have investigated several hematological parameters for their utility as predictive biomarkers for the diagnosis and prognosis of HT. Among them, the neutrophil to lymphocyte ratio (NLR), monocyte to high density lipoprotein cholesterol ratio (MHR), red cell distribution width (RDW), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and systemic immune-inflammation index (SII) have recently received attention. We searched PubMed and Embase databases (up to September 18, 2022) to assess the relationships between hematological parameters and HT. This review discusses the diagnostic and prognostic value of these hematological parameters in HT, providing an important basis for early screening, risk stratification, and optimal management of hypertensive patients. [ABSTRACT FROM AUTHOR]

Studies have consistently demonstrated associations between ultra-processed food and drink (UPFD) consumption and non-communicable diseases. However, there is a lack of data investigating relationships between UPFD intake and intermediate cardiometabolic disease markers. In this study we explored UPFD associations with lipoprotein subclasses. This was a cross-sectional study of 1986 middle-to older-aged men and women randomly selected from a large primary care centre. The percentage contribution of UPFDs to total energy intake was calculated for each participant using the NOVA classification. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses were performed to examine UPFD intake relationships with lipoprotein subclasses. In fully adjusted regression models, higher UPFD consumption was associated with reduced high-density lipoprotein (HDL) cholesterol concentrations (β = −0.024, p = 0.001), large low-density lipoprotein (LDL) levels (β = −18.645, p = 0.002), total and medium HDL concentrations (β = −0.328, p = 0.012; β = −0.510, p < 0.001), smaller LDL and HDL size (β = −0.026, p = 0.023; β = −0.023, p = 0.024), and increased medium very low-density lipoprotein levels (β = 0.053, p = 0.022), small LDL and HDL concentrations (β = 20.358, p = 0.02; β = 0.336, p = 0.011), and higher lipoprotein insulin resistance scores (β = 0.048, p = 0.012), reflecting greater lipoprotein-related insulin resistance. Findings from this research suggest that increased intake of UPFDs is associated with a more pro-atherogenic, insulin-resistant metabolic profile in middle-to older-aged adults which may be a potential mechanism underlying reported associations between UPFD consumption and chronic disease risk and mortality. [ABSTRACT FROM AUTHOR]

Cell-death-inducing DNA fragmentation factor-alpha (DFFA)-like effector b (CIDEB) was first identified as an apoptosis-inducing protein. Further research revealed a pivotal role in lipid metabolism, regulating very-low-density lipoprotein (VLDL), lipid droplets (LD), sterol response element-binding protein (SREBP), and chylomicrons. Recent studies have uncovered that rare germline variants in CIDEB protect against liver diseases, including MAFLD, cirrhosis, and viral hepatitis. Furthermore, CIDEB influences steps of the hepatitis C virus (HCV) replication cycle. This review summarizes the current knowledge about CIDEB's roles in apoptosis, lipid metabolism, and viral hepatitis, and highlights its critical role in liver diseases. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration. Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing–remitting, and 91 progressive MS patients. The spectra were analyzed to obtain concentrations of lipoprotein sub-classes, glycated acute-phase proteins, and small-molecule metabolites, including leucine, valine, isoleucine, alanine, and citrate. Composite indices for inflammatory vulnerability, metabolic malnutrition, and metabolic vulnerability were computed. MS disability was measured on the Expanded Disability Status Scale. MRI measures of lesions and whole-brain and tissue-specific volumes were acquired. Results: Valine, leucine, isoleucine, alanine, the Inflammatory Vulnerability Index, the Metabolic Malnutrition Index, and the Metabolic Vulnerability Index differed between healthy control and MS groups in regression analyses adjusted for age, sex, and body mass index. The Expanded Disability Status Scale was associated with small HDL particle levels, inflammatory vulnerability, and metabolic vulnerability. Timed ambulation was associated with inflammatory vulnerability and metabolic vulnerability. Greater metabolic vulnerability and inflammatory vulnerability were associated with lower gray matter, deep gray matter volumes, and greater lateral ventricle volume. Conclusions: Serum-biomarker-derived indices of inflammatory and metabolic vulnerability are associated with disability and neurodegeneration in MS. [ABSTRACT FROM AUTHOR]

Background: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in preanalytical requirements, methods, nomenclature, and reporting work flows. Content: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. Summary: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases. [ABSTRACT FROM AUTHOR]

Despite great progress in understanding lipoprotein physiology, there is still much to be learned about the genetic drivers of lipoprotein abundance, composition, and function. We used ion mobility spectrometry to survey 16 plasma lipoprotein subfractions in 500 Diversity Outbred mice maintained on a Western-style diet. We identified 21 quantitative trait loci (QTL) affecting lipoprotein abundance. To refine the QTL and link them to disease risk in humans, we asked if the human homologs of genes located at each QTL were associated with lipid traits in human genome-wide association studies. Integration of mouse QTL with human genome-wide association studies yielded candidate gene drivers for 18 of the 21 QTL. This approach enabled us to nominate the gene encoding the neutral ceramidase, Asah2, as a novel candidate driver at a QTL on chromosome 19 for large HDL particles (HDL-2b). To experimentally validate Asah2, we surveyed lipoproteins in Asah2-/- mice. Compared to wild-type mice, female Asah2-/- mice showed an increase in several lipoproteins, including HDL. Our results provide insights into the genetic regulation of circulating lipoproteins, as well as mechanisms by which lipoprotein subfractions may affect cardiovascular disease risk in humans.

Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.

Background Accurate lipid profile assessment, mainly low-density lipoprotein cholesterol (LDL-C) measurement, is crucial for diagnosing and managing cardiovascular disease (CVD). The widely used Friedewald formula for LDL-C calculation has limitations, prompting the exploration of alternative equations. Aims This study aims to compare ten LDL-C calculation formulas with direct measurement among study participants attending a tertiary care centre. Materials and Methods Conducted from September 2021 to July 2022 at a tertiary healthcare centre in India, the study involved 114 participants aged 18 years or older. The exclusion criteria were high-serum triglyceride (TG) levels, renal failure, diabetes, liver diseases or unwillingness to participate. Blood samples were analysed for total cholesterol, TG, high-density lipoprotein cholesterol and LDL-C. The very-low-density lipoprotein cholesterol level was calculated. The LDL-C formulas evaluated were Friedewald, Anandaraja, De Cordova, Vujovic, Ahmadi, Puavillai, Chen, Hattori, Martin–Hopkin and Sampson. Results Vujovic’s formula showed a negligible mean difference and strong correlation (r = 0.916, P < 0.001) with direct LDL-C estimation across TG concentrations. Sampson’s formula performed best for TG

Abstract Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals.

Adaptive restructuring gets disrupted due to a reduction in the body’s reserve capacity at increased stress on the functional systems in response to the combined effects of adverse factors, including climatic. Determination of the state of blood transport systems and immune homeostasis broadens our understanding of how human body systems operate under adverse conditions of the North. The purpose of this article was to assess the state of the transport components of the blood system in relation to the immune status of the population of the European North of Russia. Materials and methods. A survey of 789 residents of the Arkhangelsk Region aged 21 to 55 years was conducted and their blood system parameters were analysed taking into account the levels of haptoglobin, transferrin, immunoglobulins and lipid transport complexes with their structural ligands. Results. Residents of the European North of Russia showed increased levels of transferrin in 31.8 %, IgM in 7.6 %, IgE in 7.8 % and low-density lipoproteins in 10.2 % of cases, as well as a deficit in IgA in 55.6 % and high-density lipoprotein apoA-I ligand in 56.2 % of cases. Elevated blood transferrin concentrations are associated with low CD71+ lymphocyte count, which reflects the inhibition of activation and proliferation processes when the signal from the CD3+ receptor is blocked. A decrease in the level of transferrin CD71+ receptors on lymphocytes is manifested in disturbed immunoglobulin class switching with the formation of IgA deficit, which is compensated by IgM and IgE. Increased immunoglobulin content ensures effective binding of metabolic products with autoantigen properties (low-density lipoproteins) when the functional properties of high-density lipoproteins are impaired due to the structural apoA-I deficit. Determination of the transport components of the blood system in relation to the state of the immune system is informative for assessing the risk of disruption of adaptive mechanisms.

Background: This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries. Methods: This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression. Results: Overall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value >1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value >1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value >1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (P

Abstract Background Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). Methods The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. Results After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P

Elevated blood cholesterol and triglyceride levels induced by secondary causes are frequently observed. The identification and appropriate handling of these causes are essential for secondary dyslipidemia treatment. Major secondary causes of hypercholesterolemia and hypertriglyceridemia include an unhealthy diet, diseases and metabolic conditions affecting lipid levels, and therapeutic side effects. It is imperative to correct secondary causes prior to initiating conventional lipid-lowering therapy. Guideline-based lipid therapy can then be administered based on the subsequent lipid levels.

Lipoprotein lipase (LPL), the enzyme that carries out the lipolytic processing of triglyceride-rich lipoproteins (TRLs), is synthesized by adipocytes and myocytes and secreted into the interstitial spaces. The LPL is then bound by GPIHBP1, a GPI-anchored protein of endothelial cells (ECs), and transported across ECs to the capillary lumen. The assumption has been that the LPL that is moved into capillaries remains attached to GPIHBP1 and that GPIHBP1 serves as a platform for TRL processing. In the current studies, we examined the validity of that assumption. We found that an LPL-specific monoclonal antibody (mAb), 88B8, which lacks the ability to detect GPIHBP1-bound LPL, binds avidly to LPL within capillaries. We further demonstrated, by confocal microscopy, immunogold electron microscopy, and nanoscale secondary ion mass spectrometry analyses, that the LPL detected by mAb 88B8 is located within the EC glycocalyx, distant from the GPIHBP1 on the EC plasma membrane. The LPL within the glycocalyx mediates the margination of TRLs along capillaries and is active in TRL processing, resulting in the delivery of lipoprotein-derived lipids to immediately adjacent parenchymal cells. Thus, the LPL that GPIHBP1 transports into capillaries can detach and move into the EC glycocalyx, where it functions in the intravascular processing of TRLs.

AimsWe examined associations between lipoprotein subfractions and prevalent and incident T2D in two race/ethnically diverse cohort studies.MethodsAdults self-identifying as White, Black, Chinese, Hispanic and South Asian-American without cardiovascular disease, with fasting serum, demographic, and clinical data at enrollment and after 5 years of follow-up were included. Lipoprotein subfractions were measured at enrollment using NMR spectrometry. LASSO regularized logistic regression models adjusted for age, sex, race/ethnicity, lipid-lowering agent use, and waist circumference assessed odds of incident T2D in pooled analyses.ResultsThere were 4474 participants with lipoprotein subfraction data at enrollment and 3839 participants without prevalent diabetes, mean age 62 years, 51 % women, with 234 incident T2D cases at 5 years. Triglycerides in small, dense LDL-5 [OR 1.26 (95 % CI 1.11,1.43)], VLDL triglycerides 1.30** [1.16,1.46] and phospholipids in VLDL-1 [OR 1.31 (1.17,1.47)] were associated with higher odds of incident T2D, while free cholesterol in large HDL-1 [OR 0.75 (95 % CI 0.63,0.89)] was inversely associated. The results were similar for prevalent diabetes and did not vary by race/ethnic group.ConclusionsComposition of lipoprotein subfractions is differentially associated with prevalent and incident T2D without difference by race/ethnic group. Assessment of lipoprotein composition may enhance targeted risk reduction for T2D.

Purpose of reviewEmerging evidence supports the promise of precision nutritional approaches for cardiovascular disease (CVD) prevention. Here, we discuss current findings from precision nutrition trials and studies reporting substantial inter-individual variability in responses to diets and dietary components relevant to CVD outcomes. We highlight examples where early precision nutrition research already points to actionable intervention targets tailored to an individual's biology and lifestyle. Finally, we make the case for high-density lipoproteins (HDL) as a compelling next generation target for precision nutrition aimed at CVD prevention. HDL possesses complex structural features including diverse protein components, lipids, size distribution, extensive glycosylation, and interacts with the gut microbiome, all of which influence HDL's anti-inflammatory, antioxidant, and cholesterol efflux properties. Elucidating the nuances of HDL structure and function at an individual level may unlock personalized dietary and lifestyle strategies to optimize HDL-mediated atheroprotection and reduce CVD risk.Recent findingsRecent human studies have demonstrated that HDL particles are key players in the reduction of CVD risk. Our review highlights the role of HDL and the importance of personalized therapeutic approaches to improve their potential for reducing CVD risk. Factors such as diet, genetics, glycosylation, and gut microbiome interactions can modulate HDL structure and function at the individual level. We emphasize that fractionating HDL into size-based subclasses and measuring particle concentration are necessary to understand HDL biology and for developing the next generation of diagnostics and biomarkers. These discoveries underscore the need to move beyond a one-size-fits-all approach to HDL management. Precision nutrition strategies that account for personalized metabolic, genetic, and lifestyle data hold promise for optimizing HDL therapies and function to mitigate CVD risk more potently. While human studies show HDL play a key role in reducing CVD risk, recent findings indicate that factors such as diet, genetics, glycosylation, and gut microbes modulate HDL function at the individual level, underscoring the need for precision nutrition strategies that account for personalized variability to optimize HDL's potential for mitigating CVD risk.

In recent years, various approaches have been undertaken to eliminate lipoproteins co‐isolated with extracellular vesicles, as they were initially regarded as contaminating entities. However, novel discoveries are reshaping our perspective. In body fluids, these distinct particles not only co‐exist, but also interactions between them are likely to occur. Extracellular vesicles and lipoproteins can associate with each other, share cargo, influence each other's functions, and jointly have a role in the pathomechanisms of diseases. Additionally, their association carries important implications for therapeutic and pharmacological aspects of lipid‐lowering strategies. Extracellular vesicles and lipoprotein particles may have roles in the elimination of each other from the circulation. The objective of this minireview is to delve into these aspects. Here, we show that under certain physiological and pathological conditions, extracellular vesicles and lipoproteins are 'partners' rather than 'strangers' or 'rivals'. [ABSTRACT FROM AUTHOR]

Aim: Whether apolipoproteins (apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 [ApoB/ApoA1] ratio) or very‐low‐density lipoprotein (VLDL) cholesterol are better risk predictors than established lipid risk markers, and whether there are sex differences, is uncertain, both in general populations and in patients with diabetes. The aim of this study was to assess the association between established risk markers, apolipoproteins and the risk of macro‐ and microvascular disease and death in a large study of women and men with diabetes and to assess the potential sex differences in the associations. Materials and Methods: Established lipid risk markers were studied in 11 140 individuals with type 2 diabetes from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified‐Release Controlled Evaluation (ADVANCE) trial, and apolipoproteins (A1, B, ApoB/ApoA1 ratio) and VLDL cholesterol from nuclear magnetic resonance (NMR) lipid analyses in biobanked samples from 3586 individuals included in the ADVANCE case‐cohort study (ADVANCE CC). Primary outcomes were major macro‐ and microvascular events and death. Cox proportional hazards models adjusted for confounders were used to quantify the associations (hazard ratio [HR] and 95% confidence intervals [CIs]) between established lipid risk markers and apolipoproteins with study outcomes. To address potential effect modification by sex, we investigated the association between the lipid risk markers and outcomes in subgroup analyses by sex. Results: There was a lower risk of macrovascular complications for high‐density lipoprotein (HDL) cholesterol (HR [95%CI] 0.88 [0.82–0.95]), a higher risk for total cholesterol (1.10 [1.04–1.17]), low‐density lipoprotein (LDL) cholesterol (1.15 [1.08–1.22]), non‐HDL cholesterol (1.13 [1.07–1.20]) and the total cholesterol/HDL ratio (1.20 [1.14–1.27]) but no significant associations with triglycerides from ADVANCE. There was a higher risk of macrovascular complications for the ApoB/ApoA1 ratio (1.13 [1.03–1.24]) from the ADVANCE CC. Only the ApoB/ApoA1 ratio (1.19 [1.06–1.34]), but none of the established lipid risk markers, was associated with a higher risk of microvascular complications. There were no statistically significant sex differences for any of the established lipid risk markers or apolipoproteins with any outcome. Using C‐statistics and net reclassification improvement (NRI) did not detect significant improvement in predicting all outcomes by adding lipids or apolipoproteins to the models with confounding factors only. Conclusions/Interpretation: All established lipid risk markers, except triglycerides, were predictors of macrovascular complications, but not microvascular complications, in patients with type 2 diabetes. The ApoB/ApoA1 ratio was associated with major macro‐ and microvascular complications, but there was no evidence that apolipoproteins are better than established lipid risk markers in predicting cardiovascular complications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Atherosclerosis was found in humans who lived thousands years ago. Paleopathologist Marc Armand Ruffer (1859-1917) identified atherosclerotic plaques in the aorta as well as in several large arteries of numerous Egyptian mummies, noting that atherosclerosis was a widespread disease in antiquity. Russian researchers tried to induce experimental atherosclerosis in an animal model, feeding laboratory animals with pure cholesterol. They demonstrated that cholesterol alone caused atherosclerotic lesions in the artery wall. Many studies have shown that blood cholesterol levels are largely determined by the amount of fat in the diet. The Study of the Seven Countries was the first epidemiological evidence that linked the increase in cholesterol to cardiovascular events. In the genetic approach, one of the first indications that coronary artery disease was related to cholesterol came from anecdotal case reports of children with xanthomas (large deposits of lipids just under the skin or attached to tendon sheaths, on the back of the hands or ankles), who had sudden death or myocardial infarction before the age of 10 years. The first cases of homozygous familial hypercholesterolemia were described. The 2019 European Guideline, for example, considers for high-risk patients, a target LDL-c < 70 mg/dl and a reduction > 50% compared to baseline; for very high risk, a target LDL-c < 55 mg/dl and a reduction > 50% compared to baseline; and for patients with acute coronary syndrome, within a two-year period, a target LDL< 40 mg/dl. In order to achieve these more aggressive goals, the combination of drugs is necessary, especially in patients with eligibility criteria for the new lipid-lowering drugs, based on molecular biology techniques, in addition to an adequate clinical judgment.

Purpose: To establish prognostic biomarkers of non-prolefarative diabetic retinopathy (NPDR) progression in T2DM on the basis of examination of clinical, ophthalmological and laboratory (carbohydrate and lipid metabolism and coagulation and hemostasis) characteristics. Methods: This study included 358 T2DM2 patients with diabetic retinopathy (DR); for each patient, the eye with more severe DR was included in the study. Cases were dichotomized into three groups based on DR severity: group 1 (NPDR; 189 eyes), group 2 (preproliferative DR or PPDR; 96 eyes), and group 3 (proliferative DR or PDR; 73 eyes). Central retinal thickness (CRT; µm) and central retinal volume (CRV) were assessed by optical coherence tomography (OCT; mm3). Serum samples were taken to assess fasting serum glucose, glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and fibrinogen. Coagulation and hemostasis parameters were assessed. Statistical analyses were performed with EZR version 1.54. Results: Associations of the variables with the risk of NPDR progression were confirmed by a univariate logistic regression analysis. The area under curve (AUC) was largest for HbA1c (AUC = 0.84), followed by CRT and CRV (AUC = 0.79). In addition, the AUC ranged from 0.56 to 0.67 for the rest of variables. Age, gender, diabetes duration, and blood HDL level were not associated with NPDR progression. Our multivatiate logistic regression analysis found six biomarkers (age, HbA1c, LDL, VLDL, prothrombin index and CRT) directly associated with the risk of NPDR progression (AUC = 0.91; p < 0.001). The established association was mostly due to the three independent variables, HbA1c, VLDL and CRT (AUC = 0.90; p < 0.001). Conclusion: Independent effects on the risk of NPDR progression were confirmed for HbA1c, VLDL and CRT. The built model was found to be of very high predictive quality, which allowed recommending it for confirming high risk for NPDR progression in equivocal clinical cases or as a criterion for conclusive prognosis in the relevant expert systems.