Dyslipidemia Research Articles

EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challengingclinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Glucagon-like peptide (GLP)-1 regulation of lipid and lipoprotein metabolism.

Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins. Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity, metabolic syndrome, and type 2 diabetes. Evidence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dyslipidemia is the overproduction of hepatic and intestinal apolipoprotein (apo)B-containing lipoprotein particles. These particles are catabolized down into highly proatherogenic remnants, which can be taken up into the arterial intima and promote plaque development. Several gut-derived peptides have been identified as key regulators of energy metabolism; one such peptide is the incretin hormone glucagon-like peptide (GLP)-1. Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion. Moreover, we have demonstrated that GLP-1 receptor (GLP-1R) agonists can ameliorate diet-induced dyslipidemia. Recently, we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects. Furthermore, we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein production. Overall, ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein production and identifies other gut-derived peptides as novel regulators of postprandial lipemia. Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of diabetic dyslipidemia.

Metabolic abnormalities in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2

Background. It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect hepatocytes. At the same time, overweight and obesity are surrogate markers of the adverse effects of coronavirus disease 2019 (COVID-19). The purpose of the study: to evaluate changes in lipid and carbohydrate metabolism and their indices in the serum of patients with non-alcoholic fatty liver disease (NAFLD) with an immune response to SARS-CoV-2. Materials and methods. We studied 37 patients with NAFLD who had IgG to SARS-CoV-2. All patients were divided into two groups: group I consisted of 19 participants who were PCR-negative for SARS-CoV-2, group II included 18 patients who had COVID-19, as confirmed by PCR testing. The content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient, insulin resistance indices (HOMA-IR), TG to glucose (TG/Gly) and TG to HDL-C (TG/HDL-C) ratio were assessed in all patients. Results. Among patients with NAFLD with an immune response to SARS-CoV-2, dyslipidemia manifested by a probable increase in the median TG content in groups I and II by 2.5 and 3.4 times (р = 0.0001), respectively; TC — by 1.2 times (р = 0.0425) in both groups, with a tendency to increase; VLDL-C — by 1.8 (р = 0.010) and 2.5 times (р = 0.0022), respectively, and a decrease in the median content of HDL-C by 1.7 (р = 0.0016) and 1.9 times (р = 0.0008), respectively, in blood serum. The identified changes led to a statistically significant increase in the median atherogenicity coefficient in groups I and II — by 2.2 (р = 0.0036) and 2.5 times (р = 0.007). An increase in the HOMA-IR did not have a statistically significant difference between the groups: in group I, this index increased by 3.1 times (p < 0.05) compared with the controls, in group II — by 3 times (p < 0.05). In addition, patients in both groups had a statistically significant increase in TG/Gly and TG/HDL-C ratio compared to controls. However, the detected changes were more pronounced in group II, where TG/Gly and TG/HDL-C levels were 1.5 (р = 0.038) and 1.9 times (р = 0.035), respectively, higher than in group I. Conclusions. Patients with an immune response to SARS-CoV-2 with NAFLD have disorders of lipid and carbohydrate metabolism. At the same time, the signs of dyslipidemia were more pronounced in participants with a history of SARS-CoV-2. TG/Gly and TG/HDL-C ratio should be included in the diagnostic algorithm for assessing insulin resistance in patients with COVID-19 who are overweight or obese.

Myricanol improves metabolic profiles in dexamethasone induced lipid and protein metabolism disorders in mice

Myricanol (MY) is one of the main active components from bark of Myrica Rubra. It is demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5’-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 and AMPK are widely involved in the metabolism of nutrients, we speculated that MY may exert beneficial effects on DEX-induced metabolic disorders. This study for the first time applied widely targeted metabolomics to investigate the beneficial effects of MY on glucose, lipids, and protein metabolism in DEX-induced metabolic abnormality in mice. The results showed that MY significantly reversed DEX-induced soleus and gastrocnemius muscle weight loss, muscle fiber damage, and muscle strength loss. MY alleviated DEX-induced metabolic disorders by increasing SIRT1 and glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented muscle cell apoptosis and atrophy by inhibiting caspase 3 cleavages and muscle ring-finger protein-1 (MuRF1) expression. Metabolomics showed that MY treatment reversed the serum content of carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids and their metabolites, and 16 glycerolipids in DEX mice. Kyoto encyclopedia of genes and genomes (KEGG) and metabolic set enrichment analysis (MSEA) analysis revealed that MY mainly affected metabolic pathways, glycerolipid metabolism, lipolysis, fat digestion and absorption, lipid and atherosclerosis, and cholesterol metabolism pathways through regulation of metabolites involved in glutathione, butanoate, vitamin B6, glycine, serine and threonine, arachidonic acid, and riboflavin metabolism. Collectively, MY can be used as an attractive therapeutic agent for DEX-induced metabolic abnormalities.

Pre-treatment risk predictors of valproic acid-induced dyslipidemia in pediatric patients with epilepsy.

Background: Valproic acid (VPA) stands as one of the most frequently prescribed medications in children with newly diagnosed epilepsy. Despite its infrequent adverse effects within therapeutic range, prolonged VPA usage may result in metabolic disturbances including insulin resistance and dyslipidemia. These metabolic dysregulations in childhood are notably linked to heightened cardiovascular risk in adulthood. Therefore, identification and effective management of dyslipidemia in children hold paramount significance. Methods: In this retrospective cohort study, we explored the potential associations between physiological factors, medication situation, biochemical parameters before the first dose of VPA (baseline) and VPA-induced dyslipidemia (VID) in pediatric patients. Binary logistic regression was utilized to construct a predictive model for blood lipid disorders, aiming to identify independent pre-treatment risk factors. Additionally, The Receiver Operating Characteristic (ROC) curve was used to evaluate the performance of the model. Results: Through binary logistic regression analysis, we identified for the first time that direct bilirubin (DBIL) (odds ratios (OR) = 0.511, p = 0.01), duration of medication (OR = 0.357, p = 0.009), serum albumin (ALB) (OR = 0.913, p = 0.043), BMI (OR = 1.140, p = 0.045), and aspartate aminotransferase (AST) (OR = 1.038, p = 0.026) at baseline were independent risk factors for VID in pediatric patients with epilepsy. Notably, the predictive ability of DBIL (AUC = 0.690, p < 0.0001) surpassed that of other individual factors. Furthermore, when combined into a predictive model, incorporating all five risk factors, the predictive capacity significantly increased (AUC = 0.777, p < 0.0001), enabling the forecast of 77.7% of dyslipidemia events. Conclusion: DBIL emerges as the most potent predictor, and in conjunction with the other four factors, can effectively forecast VID in pediatric patients with epilepsy. This insight can guide the formulation of individualized strategies for the clinical administration of VPA in children.

IJCM_168A: Cardiovascular disorder risk among the police personnel in Ernakulam District, Kerala, India

Background: Appropriate assessment and management of cardiovascular risk is vital in reducing the occurrence of fatal and non fatal cardiovascular events like stroke or myocardial infarction in high risk occupational group such as Police personnel. Several studies have reported high prevalence of risk factors of cardiovascular diseases (CVD) such as hypertension, high blood lipids, physical inactivity, obesity, positive family history etc among police personnel Objective: To estimate the 10-year risk of cardiovascular events (fatal or non-fatal) among police personnel in Ernakulam City, Kerala, India Methodology: A cross sectional study was carried out among police personnel in various police stations of the district. All the police stations in the district were listed and selected randomly using the MS Excel random number generator. After getting prior permission from the concerned authorities in the Police department, Police personnel above the age of 40 years in Ernakulam city were screened for CVD risk using the WHO – non-laboratory-based CVD risk chart. Data was entered into Microsoft Office Excel and analysed using Jamovi version 2.3.28 Results: Out of 246 participants studied, the mean age was 48.4 + 3.97. Less than half of the participants (44.3%) were Civil Police Officers (CPO) or Senior Civil Police Officer (SCPO). About a third of the participants (32.1%) were having CVD risk in yellow category (5-&lt;10%), 3.3% in orange category (10-&lt;20%) and majority (64.6%) in green category (&lt;5%). On multivariate analysis, age&gt;50 years (OR – 3.36[1.73,6.5]) and duration of service&gt;20 years (OR – 4.9[2.35,10.23] were the independent determinants of higher CVD risk (yellow and orange category) Conclusion: About 35% of the participants belonged to higher risk category (yellow and orange) and duration of service&gt;20 years, age&gt;50 years were the independent determinants

Screening for familial hypercholesterolemia in Sri Lanka: A laboratory-based multicenter study

Background: Familial hypercholesterolemia (FH) is a genetic lipid disorder characterized by increased concentrations of low-density lipoprotein cholesterol (LDL-C) in the circulatory system, resulting in a markedly increased vulnerability in the development of atherosclerotic cardiovascular disease at an early age. The prevalence of FH in a Sri Lankan setting was identified in a tertiary hospital laboratory and a primary care family practice laboratory by performing opportunistic screening for index cases using laboratory criteria as a starting point. Methodology: This study assessed the prevalence of FH using the Dutch Lipid Clinic Network (DLCN) Criteria score. The evaluation was conducted over 6 months in both a tertiary hospital laboratory and a primary care laboratory. Once patients were identified by high LDL, the patients were recruited to the study and assessed clinically. Secondary causes were excluded, and clinical evaluations of the patients were done to see if they had clinical features of FH. Results: Of the total of 3039 serum lipid profiles that were reviewed, there were 42 (1.38%) lost to follow-up. There were 72 samples with high LDL (190 mg/dL) ≥4.9 mmol/L (190 mg/dL). Of the patients with LDL &gt;4.9 mmol/L, 16 (0.52%) cases with identified secondary causes (untreated hypothyroidism [n = 13], nephrotic syndrome [n = 3], and no secondary investigations [n = 14]) were excluded. In total, the point prevalence of likely phenotypical FH based on DLCN (probable or confirmed) and an LDL-C &gt;4.9 mmol/L was calculated as approximately 14/3039 (1:217). Conclusions: The point prevalence of FH in patients undergoing lipid profile testing in a tertiary hospital laboratory and a primary care laboratory was 1:217 which is comparable with the prevalence of FH in the general population in the world (based on 1 in 200–250). Based on the laboratory criteria, initiating screening for FH in resource-limited settings could be an effective screening strategy to identify patients with FH. Until national screening programs are established, the laboratory as an avenue to trigger screening for FH is useful in lower-middle-income countries like Sri Lanka.

Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas.

Infections with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst HAART regimens, darunavir and atazanavir, tenofovir disoproxil fumarate, nevirapine, rilpivirine, and especially integrase inhibitors have demonstrated the most favorable lipid profile, emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates, or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

17 variants interaction of Wnt/β-catenin pathway associated with development of osteonecrosis of femoral head in Chinese Han population

The genes of Wnt/β-catenin pathway may have potential roles in fat accumulation of Non-traumatic osteonecrosis of the femoral head (ONFH), but the effects of their variants in the pathway on ONFH development have been remained unclear. To explore the potential roles of the variants in the development of ONFH, we completed the investigation of the paired interactions as well as their related biological functions of 17 variants of GSK3β, LRP5, and FRP4 genes etc. in the pathway. The genotyping of the 17 variants were finished by MASS ARRAY PLATFORM in a 560 ONFH case–control system. The association of variants interactions with ONFH risk and clinical traits was evaluated by logistic regression analysis etc. and bioinformatics technology. The results showed that the genotype, allele frequency, and genetic models of Gsk3β rs334558 (G/A), SFRP4 rs1052981 (A/G), and LRP5 rs312778 (T/C) were significantly associated with the increased and decreased ONFH risk and clinical traits, respectively (P < 0.001–0.0002). Particularly, the paired interactions of six variants as well as eight variants also showed statistically increased and decreased ONFH risk, bilateral hip lesions risk and stage IV risk of ONFH, respectively (P < 0.044–0.004). Our results not only at the first time simultaneously showed exact serum lipid disorder and abnormal platelet function of ONFH in the same study system with the 17 variants polymorphisms of Wnt/β-catenin pathway but also shed light on the variants closely intervening the lipid disorder and abnormal coagulation of ONFH.

Platelet proteomic profiling in sitosterolemia suggests thrombocytopenia is driven by lipid disorder and not platelet aberrations

AbstractSitosterolemia is a rare autosomal recessive genetic disorder in which patients develop hypercholesterolemia and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in the intestinal hyperabsorption of all sterols, including cholesterol and, more specifically, plant sterols or xenosterols, as well as in the impaired ability to excrete xenosterols into the bile. It remains unknown how and why some patients develop hematologic abnormalities. Only a few unrelated patients with hematologic abnormalities at the time of diagnosis have been reported. Here, we report on 2 unrelated pedigrees who were believed to have chronic immune thrombocytopenia as their most prominent feature. Both consanguineous families showed recessive gene variants in ABCG5, which were associated with the disease by in silico protein structure analysis and clinical segregation. Hepatosplenomegaly was absent. Thrombopoietin levels and megakaryocyte numbers in the bone marrow were normal. Metabolic analysis confirmed the presence of strongly elevated plasma levels of xenosterols. Potential platelet proteomic aberrations were longitudinally assessed following dietary restrictions combined with administration of the sterol absorption inhibitor ezetimibe. No significant effects on platelet protein content before and after the onset of treatment were demonstrated. Although we cannot exclude that lipotoxicity has a direct and platelet-specific impact in patients with sitosterolemia, our data suggest that thrombocytopenia is neither caused by a lack of megakaryocytes nor driven by proteomic aberrations in the platelets themselves.

Pulmonary hypertension and metabolic disorders

This review presents current data regarding the relationship between hyperuricemia, obesity, diabetes mellitus, lipid disorders and pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH). Hyperuricemia is associated with a higher risk of developing of PAH, worse prognosis of PAH and greater severity of the patient's condition. Obesity leads to the development of pro-inflammatory and vasoconstrictor effects, hypoxia, which contributes to the progression of PH, however, the survival rate of patients with PH and overweight or obesity is higher than with normal or reduced body weight. Diabetes mellitus and concomitant insulin resistance are associated with a high risk of hospitalization for right ventricular heart failure and mortality. The presence of PAH is associated with lower values of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and probably high-density lipoprotein cholesterol (HDL-C). At the same time, higher levels of LDL-С and HDL-С in PAH and CTEPH determine a better prognosis of the disease.All metabolic disorders considered have common mechanisms of influence on PH. Further study of their pathogenetic basis will make it possible to develop unified approaches to methods of their correction in patients with various types of pulmonary hypertension.

Guidelines of the Polish Society of Laboratory Diagnosticsand the Polish Lipid Association on laboratory diagnosticsof lipid metabolism disorders. 2024

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area – the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

Mean Activated Clotting Time of Patients Receiving Intravenous Heparin and Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction.

Introduction The most prevalent cause of death is acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PPCI) has replaced thrombolysis as the recommended therapeutic option for individuals with ST-segment elevation myocardial infarction (STEMI). However, more effective anticoagulation regimes are required for PCI due to the limitations of unfractionated heparin. Objective This study aimed to ascertain the connection between the mean activated clotting time and the risk of bleeding and infarcts in individuals receiving intravenous heparin during PPCI for STEMI. Methods This was a one-year prospective observational study carried out at the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan. Results The majority (70.15%) were male, with a mean age of 56.08 ± 8.92 years. Following PPCI, the average active clotting time (ACT) was 350.56 ± 39.62 seconds (range 255 to 453), compared to the pre-PPCI mean of 504.15 ± 38.98 seconds. ACT was considerably higher in female patients, smokers, and overweight patients. The mean ACT was not significantly higher in patients with hypertension (HTN) and dyslipidemia (DLD). Conclusion The ACT range in this investigation was 255 to 453 seconds, and there was no discernible relationship between ACT readings and problems related to bleeding and ischemia. To determine who is more at risk, bleeding risk models should be used and improved further before catheterization.

Discovery of novel and selective farnesoid X receptor antagonists through structure-based virtual screening, preliminary structure-activity relationship study, and biological evaluation

Farnesoid X receptor (FXR) is a bile acids receptor and plays a crucial role in regulating bile acids, lipids, and glucose metabolism. Previous research suggests that inhibiting FXR activation can be beneficial in reducing cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, offering potential treatment options for metabolic syndrome with lipid disorders. Herein, we report p-acetylaminobenzene sulfonate derivatives as a novel scaffold of FXR antagonists by multistage screening. Among these derivatives, compound F44-A13 exhibited a half-maximal inhibitory concentration of 1.1 μM. Furthermore, compound F44-A13 demonstrated effective inhibition of FXR activation in cellular assays and exhibited high selectivity over eleven other nuclear receptors. Besides, compound F44-A13 significantly suppressed the regulation of FXR target genes Shp, Besp, and Cyp7a1, while reducing cholesterol levels in human hepatoma HepG2 cells. Pharmacological studies conducted on C57BL/6 mice further confirmed that compound F44-A13 had beneficial effects in reducing cholesterol, triglycerides, and LDL-C levels. These findings highlight that F44-A13 is a highly selective FXR antagonist that might serve as a useful molecule for further FXR studies as well as the development of FXR antagonists for the potential treatment of metabolic diseases with lipid disorders.

2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders.

Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area - the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.

Metabolic biomarkers in patients with type 2 diabetes mellitus and heart failure with preserved ejection fraction

BACKGROUND: Half of all patients with chronic heart failure (CHF) have preserved ejection fraction (CHF-nEF). The drug’s use effective for treatment of CHF with reduced ejection fraction (CHF-nFV) reduces the hospitalization incidence but does not affect the cardiovascular incidence or overall mortality in patients with CHF-nFV. Finding differences between CSN-SFV and CSN-nFV biomarkers is a pressing scientific problem.AIM: To study the metabolic disorders biomarkers intergenic relationships, myocardial damage, and to evaluate their role in the CHF development in patients with DM2.MATERIALS AND METHODS: We studied the lipid and carbohydrate metabolism disorder genes polymorphisms frequencies in patients with CHF-CFV and DM2 (48 patients), CHF-NFV and DM2 (46) and patients with metabolic syndrome (MS) without CHF (68), mean age of patients was 69,7±5,3 yo. DNA was isolated from venous blood according to the manufacturer’s methodology. Gene polymorphisms were determined by real time PCR. The studied polymorphisms correlations with clinical and laboratory data and associations between clinical and laboratory tests were identified by regression analysis.RESULTS: In the control group, PPARG, APOC3 C3238G rs5128, LIPC -250 G&gt;A rs2070895, APOA1 G-75A rs670, FABP2 Ala54Thr G&gt;A rs1799883, ADRB2 5318 C&gt;G rs1042714 genes polymorphisms, along with co-dependent ADRB3, FTO, FABP2 genes polymorphic form a gene network regulating plasma concentrations of LDL, uric acid and CAD. Gene polymorphisms have been found to be associated with clinical and/or laboratory parameters in patients with CHF-CFV: PPARGC1AGly482Ser G&gt;A rs8192678 with CAD; PPARGT-2821C rs12497191 with glycated hemoglobin level; FTO A&gt;T rs9939609 (α-ketoglutarate dependent dioxygenase gene) with waist circumference; LEPR A&gt;G rs1137101 (leptin receptor gene) with MAP. The following polymorphisms were found to be associated in patients with CHF-nFV: LIPC-250 G&gt;A rs2070895 (liver triglyceride lipase gene) with MAP; PPARGC1A Gly482Ser G&gt;A rs8192678 with MAP; FTO A&gt;T rs9939609 with waist volume.CONCLUSIONS: From the study results, it is evident that patients with DM2 having CHF with different PV differ significantly among themselves by the presence of polymorphic genes prone to network interactions. The greatest number of such interactions is observed in the group of CHF-sFV, which determines a more complex course of this variant of CHF than in patients with CHF-nFV.

Altered lipid metabolism and the development of metabolic-associated fatty liver disease.

An increasing amount of research has underscored the significant role of lipoproteins in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). This comprehensive review examines the intricate relationship between lipoprotein abnormalities and the development of MAFLD. Atherogenic dyslipidemia seen in insulin resistance states play a significant role in initiating and exacerbating hepatic lipid accumulation. There are also specific genetic factors ( PNPLA3 , TM6SF2 , MBOAT7 , HSD17B13 , GCKR- P446L) and transcription factors (SREBP-2, FXR, and LXR9) that increase susceptibility to both lipoprotein disorders and MAFLD. Most monogenic primary lipid disorders do not cause hepatic steatosis unless accompanied by metabolic stress. Hepatic steatosis occurs in the presence of secondary systemic metabolic stress in conjunction with predisposing environmental factors that lead to insulin resistance. Identifying specific aberrant lipoprotein metabolic factors promoting hepatic fat accumulation and subsequently exacerbating steatohepatitis will shed light on potential targets for therapeutic interventions. The clinical implications of interconnection between genetic factors and an insulin resistant environment that predisposes MAFLD is many fold. Potential therapeutic strategies in preventing or mitigating MAFLD progression include lifestyle modifications, pharmacological interventions, and emerging therapies targeting aberrant lipoprotein metabolism.

Systemic loss of CD36 aggravates NAFLD-related HCC through MEK1/2-ERK1/2 signaling pathway

Background & aimsCD36, a membrane protein widely present in various tissues, is crucial role in regulating energy metabolism. The rise of HCC as a notable outcome of NAFLD is becoming more apparent. Patients with hereditary CD36 deficiency are at increased risk of NAFLD. However, the impact of CD36 deficiency on NAFLD-HCC remains unclear. MethodsGlobal CD36 knockout mice (CD36KO) and wild type mice (WT) were induced to establish NAFLD-HCC model by N-nitrosodiethylamine (DEN) plus high fat diet (HFD). Transcriptomics was employed to examine genes that were expressed differentially. ResultsCompared to WT mice, CD36KO mice showed more severe HFD-induced liver issues and increased tumor malignancy. The MEK1/2-ERK1/2 pathway activation was detected in the liver tissues of CD36KO mice using RNA sequencing and Western blot analysis. ConclusionSystemic loss of CD36 leaded to the advancement of NAFLD to HCC by causing lipid disorders and metabolic inflammation, a process that involves the activation of MAPK signaling pathway. We found that CD36 contributes significantly to the maintenance of metabolic homeostasis in NAFLD-HCC.

Hypercholesterolemia: a literature review on management using tafolecimab: a novel member of PCSK9 monoclonal antibodies.

Cardiovascular diseases (CVD) persist as the leading cause of mortality globally, with atherosclerotic cardiovascular disease (ASCVD), including hypercholesterolaemia, being a significant contributor. Hyperlipidemia management includes various lipid-lowering drugs, including statins, Bempedoic acid, inclisiran, Lomitapide, ANGPTL3 inhibitors, and PCSK9 inhibitors. Statins have traditionally dominated lipid management therapies; however, a subset of patients remains unresponsive or intolerant to this therapy, necessitating novel therapeutic approaches. Tafolecimab, a promising and novel PCSK9 monoclonal antibody, demonstrated significant LDL-C reduction and a favourable safety profile in clinical trials. This review aimed to discuss the role and efficacy of Tafolecimab in the management of hypercholesterolaemia. The authors searched online databases, including PubMed, Scopus, and Embase, for articles related to talofecimab. The efficacy of Tafolecimab in diverse patient populations, including those with comorbid conditions and various lipid disorders, has been explored. Ongoing trials, such as CREDIT-1, CREDIT-2, and CREDIT-4, have provided valuable insights into Tafolecimab's potential as a lipid-lowering agent. Moreover, the drug's extended dosing interval may enhance patient compliance and reduce treatment costs. It has also been found that Tafolecimab has more affinity for PCSK9 and a longer duration of LDL-C reduction than other monoclonal antibody drugs such as evolocumab. Thus, this review focuses on Tafolecimab, a novel PCSK9 monoclonal antibody, its mechanism of action, clinical trial outcomes, safety profile, and potential role in hypercholesterolaemia management. Despite its assuring potential, the long-term impact of Tafolecimab on cardiovascular outcomes remains to be fully elucidated, necessitating further research. Regulatory authorities like the FDA and EMA should also evaluate Tafolecimab's risks and benefits. In conclusion, Tafolecimab shows potential as an innovative therapeutic option for hypercholesterolaemia, particularly in patients with specific risk factors, but warrants additional research.

Editor-in-Chief’s Top Picks From 2023

Each week, I record audio summaries for every paper in JACC, as well as an issue summary. This process has become a true labor of love due to the time they require, but I am motivated by the sheer number of listeners (16M+), and it has allowed me to familiarize myself with every paper that we publish. Thus, I have selected the top 100 papers (Original Investigations, Review Articles, Society Documents, and the Global Burden of Diseases) from distinct specialties each year. In addition to my personal choices, I have included papers that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. In order to present the full breadth of this important research in a consumable fashion, we will present these abstracts in this issue of JACC, as well as their Central Illustrations∗ and podcasts. The highlights comprise the following sections: Aorta; Basic and Translational Science; Cardiac Failure, Myocarditis, and Pericarditis; Cardiomyopathies and Genetics; Congenital Heart Disease; Coronary, Peripheral, and Structural Interventions; Coronavirus; Health Promotion and Preventive Cardiology; Imaging; Metabolic and Lipid Disorders; Neurovascular Disease and Dementia; Rhythm Disorders and Thromboembolism; and Valvular Heart Disease.1-104 ∗ To view the full manuscript, including the full-sized Central Illustration, please refer to the original publication in JACC.