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Familial hypercholesterolemia (FH) is a common genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C), leading to a high risk of early onset atherosclerotic cardiovascular disease (ASCVD). This document provides an update to the National Lipid Association's 2011 clinical guidance, summarizing the remarkable progress in the field. With a global prevalence of approximately 1 in 311, FH remains severely underdiagnosed. This guidance reviews current diagnostic criteria, including the expanding role of genetic testing to complement diagnosis and to facilitate cascade screening, and emphasizes a thorough differential diagnosis. It provides recommendations for universal pediatric screening and systematic cascade screening in families to improve detection. Management strategies include intensified LDL-C treatment goals for both primary and secondary prevention of ASCVD. A stepwise approach to optimal therapy is outlined, beginning with lifestyle interventions and pharmacotherapy with maximally tolerated statins and ezetimibe. This update incorporates newer agents, including proprotein convertase subtilisin/kexin type 9 inhibitors and bempedoic acid. Additional therapies, such as lomitapide and evinacumab for homozygous FH and lipoprotein apheresis for heterozygous and homozygous FH, are discussed. Further topics include cardiovascular imaging for risk stratification, management in specific populations and circumstances, such as planning for and during pregnancy and in pediatrics, and recognition of health disparities. This guidance equips clinicians with evidence-based strategies to improve the identification and care of patients with FH, ultimately reducing the high morbidity and mortality associated with this condition. Show less

Apolipoprotein B-100 (apoB-100) is the main structural protein of apoB-containing lipoproteins including low-density lipoprotein (LDL). Its organization or lipidation process in an apoB-containing lipoprotein particle is still unclear. To understand its organization in a LDL particle, the combination of atomic force microscopy (AFM) with lipid depletion by Nonidet P-40 (NP-40) or methyl-β-cyclodextrin (MβCD) was utilized for the first time to in situ visualize LDL delipidation process and lipid-poor/-free apoB-100 at a physiological condition. During LDL delipidation process, different morphologies/structures were visualized successively including spheroidal structure with a smaller size than native LDL, spheroidal structure with one or more holes, closed annular/circular structure, opened annular/circular structure, C/U-shaped (or horseshoe-shaped) structure, and V/S/I-shaped structure. Based on the concentration-dependent structural distributions, these structures probably reflect 5 stages of LDL delipidation (e.g., a slightly delipidated LDL stage, a partially delipidated LDL stage, a neutral lipid-poor/-free apoB-100 stage, a lipid-poor apoB-100 stage, and a lipid-free apoB-100 stage, respectively). Our findings could provide structural evidence to reconcile the previous controversy and provide potential evidence/clues/implications for understanding apoB-100 lipidation and the organization of apoB-100 in apoB-containing lipoprotein particles. Potentially, this study also can provide new structural insights into the design of food-grade lipid carriers. Moreover, the combination of AFM with lipid depletion, which has many advantages over traditional electron microscopy (e.g., label-free, in situ, and real-time imaging under physiological conditions, etc.), is a potentially ideal novel strategy for studying the structure of apolipoproteins or lipoproteins. Show less

We investigated the relationship between heart failure etiology and lipoprotein subfractions, and to explore their associations with left ventricular dimension and function in heart failure with reduced ejection fraction (HFrEF) patients. Cross-sectional investigation of serum lipoprotein subfractions from 205 HFrEF patients in the SMARTEX heart failure study. Serum levels of triglycerides, cholesterol, free cholesterol, phospholipids, lipoproteins (Apolipoproteins; A-1, A-2, and B), very-low-density (VLDL), intermediate-density (IDL), low-density (LDL), and high-density lipoprotein (HDL) were determined using Stable HFrEF patients [left ventricular ejection fraction (LVEF) ≤ 35%, NYHA class II-III], with ischemic (ICM, n = 119) or non-ischemic (NICM, n = 86) cardiomyopathy were studied. NICM patients had higher levels of 48 lipoproteins compared to ICM patients, including 29 LDL, 13 VLDL, and 6 HDL subfractions [p <0.05]. NICM patients had 22% higher cholesterol and 27% higher remnant cholesterol levels, with 24% more atherogenic ApoB containing subfractions (VLDL, IDL, LDL) (p <0.05). Heart failure etiology and statin treatment explained 23-24% of the variability in cholesterol, free cholesterol, and ApoB (p <0.001). Triglyceride content in some VLDL and LDL subfractions was weakly associated with left ventricular end-diastolic volume, end-diastolic diameter, ejection fraction, and S'. NICM patients had the highest atherosclerotic lipoprotein burden, attributed to elevated ApoB particles and partly due to less statin treatment. The triglyceride content of some VLDL and LDL subfractions was weakly associated with left ventricular structure and function. However, further research is needed to determine their prognostic significance before implementation into strategies for prevention and treatment. Show less

Lipoprotein(a) [Lp(a)] is a significant genetic risk factor for cardiovascular disease (CVD). Extremely high Lp(a) levels (153mg/dL), affecting about 1 in 100 individuals, can elevate low-density lipoprotein cholesterol (LDL-C) due to structural similarities between Lp(a) and LDL-C particles. This study assessed the role and impact of Lp(a) on LDL-C in children with hypercholesterolemia, a relationship that remains poorly understood. The study included 1,418 children (median age: 6.34 years) with hypercholesterolemia, identified by universal or cascade familial hypercholesterolemia (FH) screening in Slovenia. Participants were categorized as: 363 (25.6%) with definite FH (pathogenic variants in LDLR/APOB/PCSK9), 1,014 (71.5%) with possible FH (no FH pathogenic variant), and 41 (2.9%) definite non-FH (siblings of definite FH cases without FH pathogenic variant). Elevated Lp(a) levels (>30 mg/dL) were found in 25.1% of definite FH and 34.9% of possible FH cases (p=0.003). In definite FH, 32.7% of Lp(a) levels contributed to LDL-C levels, and 18.6% of Lp(a) levels contributed to Apolipoprotein B. The Lp(a) component of LDL-C varied widely (0-49.6%) and accounted for 10.3% of LDL-C variability. After adjusting for Lp(a), elevated LDL-C (>3.5 mmol/L) still persisted in 88.4% of definite FH and 30.4% of possible FH children. One in four children with FH and one in three children with polygenic hypercholesterolemia have elevated Lp(a) levels, contributing notably to LDL-C levels and ApoB. Modifiable CVD risk factors (elevated LDL-C and obesity) are already present in those children, highlighting the need for early, targeted evaluation and management. Show less

Childhood obesity is a severe global epidemic, and emerging evidence suggests environmental pollutants like polystyrene microplastics (PS-MPs) may disrupt metabolic homoeostasis though mechanistic insights remain limited. This study integrated cross-species transcriptomics (from zebrafish and human adipose datasets), network toxicology, machine learning, and molecular docking to explore this link. We identified 40 overlapping genes between childhood obesity related DEGs and PS-MPs related genes, enriched in lipid metabolic pathways such as cholesterol homoeostasis and insulin signalling. Topological and machine-learning analyses highlighted hub genes, which showed strong diagnostic accuracy. Molecular docking further revealed stable binding (energy < -5.0 kcal/mol) between PS-MPs and key targets (APOB、BUB1、CDC20 and PPARGC1A). Our integrative analysis suggests that PS-MPs may act as an environmental trigger that could disrupt conserved lipid and metabolic homoeostasis by targeting key hub genes (APOB、BUB1、CDC20 and PPARGC1A). These findings provide a novel molecular hypothesis linking PS-MPs exposure to childhood obesity and support precautionary measures. Show less

Apolipoprotein B (apoB) is a well-known risk factor for atherosclerosis. However, studies examining its relation to atrial fibrillation (AF) have produced conflicting results and suggested possible sex-specific differences. This study investigated the sex-specific associations between serum apoB concentrations and incident AF and offer insight into the inconsistencies in previous research. A prospective analysis of 26,803 participants without pre-existing AF was performed using data from the Malmö Diet and Cancer Study. Sex-specific associations between apoB and AF were assessed using multivariable Cox proportional hazards models. To ensure the robustness of the results, several sensitivity analyses, such as restricted cubic spline modeling, competing risks regression, alternative adjustment strategies, subgroup analyses, follow-up time restrictions, and multiple imputation for missing data, were conducted. For median follow-up periods of 21.2 and 24.8 years in men and women, respectively, 2,768 and 2,968 incident cases of AF were recorded, respectively. Among women, unadjusted models showed a strong positive association between apoB and AF, with the highest versus lowest quartile showing a hazard ratio (HR) of 1.65 (95% confidence interval [CI] 1.49–1.84; Results show sex-specific observational links between apoB concentrations and risk of AF. In women, higher apoB levels were linearly inversely associated with AF, whereas in men, the association was borderline non-linear, with inverse effects seen mainly at lower apoB concentrations. These sex differences in AF susceptibility may partly reflect underlying atrial electrophysiological variations and hormonal influences, though whether these factors directly mediate the apoB-AF association remains speculative. The online version contains supplementary material available at 10.1186/s12944-026-02905-6. Show less

Self-collection of biospecimens at-home, without specialized equipment or training, are increasingly being adopted in clinical practice due to convenience and patient preferences. However, sample instability during shipment means that remote access to common blood tests remains challenging. We hypothesized that the inaccuracy and imprecision in test results that develop because of sample instability could be modeled and controlled using knowledge of transit conditions captured by environmental sensors. We subjected 2685 blood samples from 65 participants to temperature cycles derived from real-world transit conditions. Training a model called Remote Control to predict change enabled accurate calibration of test results to approximate the time zero value at the point of collection, despite sample degradation. With calibration, unprocessed whole blood could be transported, for up to 9 days under ambient conditions and exposed to temperatures between 3.4 and 47.4 °C. Under these conditions, agreement with CLIA TEa ranged between 98.1 and 100%, with a |%bias| of 0.1-1.6%, a %CV of 2.2-4.9%, and a minimum sigma metric between 3 and 8.8σ for lipids (Cholesterol, HDL, LDL, Triglycerides, APO-A1, and APO-B). Performance was linear across measurement intervals (R Show less

Circulating apoB-containing lipoproteins fall into three principal categories- low-density lipoproteins (LDLs), triglyceride-rich lipoproteins (TRLs) and lipoprotein(a) [Lp(a)]. These three different lipoproteins are all causally related to atherosclerotic cardiovascular disease (ASCVD) and together account for the full spectrum of apoB-related atherogenic risk. They vary substantially in metabolic and kinetic properties, size and lipid composition and may affect the atherosclerotic pathogenic process differently. Indeed, genetic evidence indicates that TRLs and Lp(a) are several-fold more atherogenic per particle than LDL in terms of ASCVD risk. On the other hand, Lp(a) and TRLs are typically much less abundant than LDL. How should these countervailing factors be balanced to understand their net contribution to risk? In this review, we summarize the evidence relating to the atherogenicity of LDLs, TRLs and Lp(a) and explore the implications for risk stratification and therapeutic strategies. We argue that LDL lowering will remain the cornerstone of apoB-related risk reduction, but eradication of residual risk necessitates combination therapies targeting TRLs and/or Lp(a) in addition to LDL. Show less

Hydroxychloroquine (HCQ) is an immunomodulatory agent used in autoimmune conditions. Observational studies suggest that HCQ may lower circulating cholesterol and triglyceride levels, indicating a potential cardiovascular benefit. However, the specific changes in lipoprotein particle concentrations driving these effects have not been characterized in detail. To evaluate the effects of HCQ on circulating lipids and on lipoprotein concentration and composition. A post hoc analysis was conducted within a randomized, placebo-controlled, double-blind trial investigating the effects of HCQ on glucose metabolism in adults at risk for type 2 diabetes. Outcomes were analyzed as changes from baseline (placebo-adjusted) using mixed-effects models, with adjustments for sex, age, body mass index, and statin use. Compared with placebo, HCQ reduced total cholesterol (10.4%), low-density lipoprotein (LDL) cholesterol (12.9%), and non-high-density lipoprotein (HDL) cholesterol (15.0%). LDL particle concentration decreased by 15.1% and apolipoprotein B (ApoB) by 9.7%. HCQ had no effect on HDL cholesterol, HDL particle concentration, or apolipoproteinA1 (ApoA1). However, small HDL particle concentrations fell by 20.0%, while large HDL particle concentrations increased by 17.1%. HCQ reduced triglycerides by 27.8%, which was associated with a 20.6% reduction in triglyceride content per very low-density lipoprotein (VLDL) particle. Lipoprotein(a) levels were unaffected. HCQ changes lipoprotein concentration and composition, though the effects are distinct for each lipoprotein class. Our results suggest that HCQ lowers total cholesterol by reducing LDL particle concentration, decreases triglyceride by reducing the triglyceride content of VLDL particles, and alters the relative distribution of small vs large HDL particle concentration. These findings suggest protective benefits against atherosclerosis that warrant further investigation. Show less

Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial was conducted to investigate the acute effects of a single episode of alcohol ingestion on various biomarkers in healthy individuals. A total of 45 male participants were recruited and randomized into an alcohol group (n = 40) and a control group (n = 5) at an 8:1 ratio. Volunteers in the alcohol group ingested 40% Absolut vodka within 15 min. Blood pressure, heart rate, and blood oxygen saturation were measured at 0 h, 1 h, 3 h, 5 h, 12 h, and 24 h. Venous blood samples were drawn at 0 h, 1 h, 5 h, 12 h, and 24 h after alcohol intake. Our results showed that levels of liver function markers, including α-fucosidase (AFU), albumin (ALB), and alkaline phosphatase (ALP), were significantly increased in the alcohol group compared to the control group. The 24-h area under curve (AUC) of AFU, ALB, and ALP were significantly higher in the alcohol group. The liver fibrosis maker collagen type Ⅳ (Ⅳ-C) tended to be higher at 1 h and 12 h in the alcohol group compared to the control group. Lipid levels, including triglycerides (TG), apolipoprotein A1 (APOA1), and the APOA1/APOB, were significantly elevated after alcohol ingestion, particularly at 5 h and 12 h. The 24 h-AUC of TG, APOA1, and APOA1/APOB were higher in the alcohol group than in the control group. Additionally, cardiac function indicators, including heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were significantly elevated in the alcohol group. SBP and DBP remained higher 24 h after alcohol ingestion compared to the control group. This study demonstrated that even a single episode of binge drinking could induce significant alterations of biomarkers related to liver function, cardiac function, and lipid profiles. These findings provided valuable insights into the short-term impact of alcohol on health and highlighted the importance of further research to explore the long-term implications of repeated acute alcohol exposure. Given the very small control group, these results should be interpreted as preliminary and confirmed in larger, more balanced randomized trials. The online version contains supplementary material available at 10.1038/s41598-026-40028-1. Show less

Coronary heart disease (CHD) burden is increasing, and traditional obesity measures inadequately capture fat distribution and associated CHD risk. A body shape index (ABSI) is an emerging anthropometric metric of fat distribution, but evidence linking ABSI to CHD is limited, particularly in the Chinese population. This case-control study in southern China investigated the association of ABSI and related factors with CHD risk, aiming to facilitate early identification of high-risk individuals. We retrospectively studied 996 patients who underwent coronary angiography in a southern Chinese hospital. After strict screening and propensity score matching (PSM), 125 patients with CHD (>50% coronary stenosis) and 125 controls (<50% stenosis) were selected. Key CHD risk predictors were identified using feature-selection techniques (LASSO regression, recursive feature elimination, random forest importance). Univariate and multivariate logistic regression models were constructed for CHD prediction. Model performance was evaluated by receiver operating characteristic (ROC) analysis and compared to individual predictors using the DeLong test. A nomogram was developed for individualized risk estimation. Baseline characteristics were well matched between CHD and control groups after PSM. Across feature-selection methods, the most influential predictors for CHD included ABSI, prealbumin (PA), direct-to-total bilirubin ratio (DB/TB), apolipoprotein B (ApoB), globulin (GLO), apolipoprotein A-I (ApoA-I), and essential hypertension (EH). Each of these factors showed a significant univariate association with CHD ( This study identifies ABSI as a potential predictor of CHD risk among southern Chinese populations. Integrating ABSI with other candidate predictors improves the model's predictive performance. A multifactorial approach may better characterize CHD risk in this population and could inform prevention strategies. Show less

Researchers reported on the pathogenic role of hypercholesterolemia in thyroid orbitopathy (TO) and the use of statins in its prevention and treatment. To confirm these observations, we conducted a prospective study of patients with Graves' and Basedow's disease (GBD) to evaluate the relationship between the presence of TO and levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoproteins A1 and B (Apo A1, Apo B), along with the impact of immunosuppressive treatment on the lipid profile. Forty-seven patients with GBD diagnosed within the past 12 months were eligible for the study. In the GBD group, 31 patients were diagnosed with active TO and qualified for immunosuppressive treatment, while 16 patients did not have TO. TC, TG, HDL-C, and LDL-C levels were measured in serum using enzymatic methods, and Apo A-1 and Apo B levels were determined by immunoturbidimetric methods. The mean TC concentration in patients with active TO who qualified for immunosuppressive treatment was 207.7 ± 42.7 mg/dL, significantly higher than the values in GBD patients without TO symptoms (191.5 ± 47.8 mg/dL). After completing immunosuppressive treatment, the mean TC concentration increased to 214.3 ± 49.8 mg/dL, remaining significantly higher than before treatment. The mean LDL-C concentration in patients with active TO was 131.6 ± 40.4 mg/dL and was higher, though not significantly, compared to the GBD group without TO symptoms (122.6 ± 49.0 mg/dL). After immunosuppressive treatment, the mean LDL-C levels increased to 142.1 ± 54.5 mg/dL and were also significantly higher than before treatment. Additionally, the mean Apo B concentration in patients with active TO was significantly higher than in patients without TO. After immunosuppressive treatment, the mean Apo B concentration increased and remained significantly higher than before treatment. There was no significant difference in HDL-C, Apo A1, and TG concentrations between the groups with and without TO, nor their levels after immunosuppressive treatment. The use of statins as adjunctive therapy in GBD patients with active TO qualified for immunosuppressive treatment is reasonable due to the increase in TC, LDL-C, and Apo B levels during treatment, as well as for their pleiotropic effects, including their anti-inflammatory effects. Show less

This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and genotype and allele frequencies were compared between groups. Multivariate logistic regression analyzed the link between ApoE polymorphisms and CAD risk in populations at middle and high altitudes. The data revealed significant differences in These findings validated that the Show less

To develop and validate a prediction model for in-hospital cardiogenic shock (CS) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) based on machine learning (ML) algorithms. A total of 1608 AMI patients admitted to the First Hospital of Lanzhou University during 2023 and 2024 were retrospectively enrolled in this study. The 851 patients from 2023 were randomly divided into a training set ( LASSO regression initially identified 13 candidate features, while the random forest (RF) model demonstrated the best predictive performance in the training set. Following Boruta refinement, seven key features were retained, leading to the construction of an updated RF model. This model achieved an AUROC of 0.906, an accuracy of 0.977, a precision of 0.900, a sensitivity of 0.643, a specificity of 0.996, and a F1 score of 0.750 on the internal validation set. Temporal external validation at the same center showed an AUROC of 0.988, an accuracy of 0.967, a precision of 0.701, a sensitivity of 0.904, a specificity of 0.972, and a F1 score of 0.790. Furthermore, the model demonstrated excellent calibration, with a Brier score of 0.023 and 0.027. The SHAP analysis ranked feature importance as Killip class, D-dimer (DD), creatinine (Crea), alanine aminotransferase (ALT), apolipoprotein B/A (APOB/A), diastolic blood pressure (DBP) and lactate (Lac). We developed and validated a RF model based on seven key variables—Killip class, DD, Crea, ALT, APOB/A, DBP and Lac—that serves as a predictive tool for identifying the risk of in-hospital CS in AMI patients post-PCI. Additionally, we created an online prediction application using Streamlit, which facilitates the implementation of this model into clinical practice. Show less

Thyroid hormones regulate lipoprotein metabolism-primarily by up-regulating the LDL receptor. Whether TSH relates to LDL-C in hypercholesterolemic children, and whether this depends on familial hypercholesterolemia (FH) status or the underlying defective gene, is uncertain. We evaluated TSH-lipid associations in prepubertal children and tested effect modification by FH status and, within FH, by gene with a pathogenic variant (LDLR vs APOB). We performed a cross-sectional study of prepubertal children referred to the Slovenian national tertiary center through the universal FH screening program or cascade screening. Eligibility required concurrent TSH and fasting lipid measurement and completed genetic testing (pathogenic/likely pathogenic variants in LDLR/APOB/PCSK9 vs polygenic hypercholesterolemia). Among 738 children, 182 (24.7%) were FH-positive (LDLR 132; APOB 50). In the pooled cohort, TSH did not correlate with age or lipids (all p ≥ 0.050). After sex stratification, TSH correlated with triglycerides only in males (ρ = 0.156; p = 0.012). In FH-positive children, TSH correlated with total cholesterol, LDL-cholesterol, and ApoB (ρ ~ 0.184-0.207; all p < 0.050), with no associations in FH-negative children. Interaction testing confirmed effect modification by FH (TSH × FH β = 0.141 mmol/L per mIU/L, p = 0.023). Within FH-positive children, a positive TSH-LDL-C slope was seen in LDLR carriers (β = 0.237, p = 0.004) but not in APOB carriers (β = -0.065, p = 0.655). TSH was positively associated with LDL-C only in FH due to LDLR variants, not in APOB carriers. These findings suggest that genetic background may shape hormonal sensitivity, and that attention to thyroid status could be particularly relevant in LDLR-FH. Show less

Familial hypercholesterolemia is a monogenic Mendelian disorder characterized by elevated LDL cholesterol and premature atherosclerotic cardiovascular disease. It is caused by pathogenic variants in LDLR , APOB , and PCSK9 , with rarer involvement of LDLRAP1 and APOE . Despite advances in molecular diagnostics, no causative variant is identified in approximately 25-75% of clinically diagnosed cases. Familial hypercholesterolemia is currently defined as an autosomal semi-dominant disorder with a gene-dosage effect, whereby biallelic pathogenic variants result in markedly more severe phenotypes than heterozygous variants. Terminology for homozygous familial hypercholesterolemia has been refined. Former terms such as 'true homozygote', 'compound heterozygote', and 'double heterozygotes' have been replaced by monogenic biallelic forms, with identical or different variants, and digenic biallelic forms involving two familial hypercholesterolemia-associated genes. Polygenic risk score (PRS) and lipoprotein(a) measurement help explain familial hypercholesterolemia-like phenotypes in patients without a monogenic cause and enable determination of polygenic severe hypercholesterolemia and/or hyperlipoproteinemia(a). Although advances in molecular genetics have improved variant detection, interpretation remains challenging. Integration of case-level data and functional studies, including high-throughput LDLR assays and APOB structural analyses, has enhanced variant pathogenicity classification. Combining monogenic variant detection, PRS determination and lipoprotein(a) assessment enables comprehensive diagnosis, tailored risk stratification, and personalized familial hypercholesterolemia management. Show less

Although familial hypercholesterolemia (FH) is a US Centers for Disease Control and Prevention tier 1 condition for genetic testing, the impact of testing on clinical outcomes is unclear. We aimed to assess whether genetic testing alters lipid management in HeartCare participants. For participants with pathogenic/likely pathogenic variants for FH observed at Baylor College of Medicine cardiology clinics, data on laboratory values, medication prescriptions, and diagnoses were collected and compared before and after genetic testing. In the 20 participants with APOB/LDLR variants and complete data, low-density lipoprotein cholesterol (LDL-C) was numerically lower but not significantly different before vs after genetic testing (103 vs 79.5 mg/dL). Sixteen (80%) participants were from the lipid clinic; the majority had a preexisting FH diagnosis. LDL-C levels were numerically lower, and more patients received proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions after genetic testing; however, the difference was not statistically significant. The majority of patients with FH achieved LDL-C <100 mg/dL after genetic testing; however, most patients with APOB/LDLR variants were from the lipid clinic and had been diagnosed with FH by clinical criteria. Show less

Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects in MASLD; however, whether AITC alleviates MASLD through VDR remains unclear. To clarify the function and underlying mechanisms of AITC in MASLD AML-12 cells were exposed to 300 μM palmitate acid (PA) for 24 hours to establish an To establish an AITC provides a robust molecular basis for improving MASLD by activating hepatic VDR and driving the downstream HNF-4α/MTTP/ApoB signaling pathway. This pathway reduces hepatic lipid accumulation, promotes FA β-oxidation, and improves insulin resistance, establishing AITC as a promising treatment for MASLD. Show less

Despite significant advances in lipid-lowering therapeutics, residual lipid risk persists in patients with or at risk of atherosclerotic cardiovascular disease (ASCVD), even after optimizing low-density lipoprotein (LDL) cholesterol. Emerging evidence highlights the role of non-LDL cholesterol fractions, such as remnant cholesterol, lipoprotein(a) [Lp(a)], apolipoprotein B (apoB), and non-high-density lipoprotein (HDL) cholesterol, as key contributors to residual ASCVD risk. Remnant cholesterol, Lp(a), and LDL cholesterol represent three independent lipoprotein species causing ASCVD, while apolipoprotein B (apoB) and non-HDL cholesterol integrate the other three variables. Thus, clinically interpreting elevated apoB and non-HDL cholesterol is potentially complicated since remnants, Lp(a), and LDL cause ASCVD by different mechanisms and by varying proportions in different patients. Indeed, recent research into the pathophysiology of lipid-driven atherogenesis and development of ASCVD has revealed novel mechanisms that in turn suggest new therapeutic strategies targeting non-LDL lipid components. Elevated remnant cholesterol jointly with elevated LDL cholesterol contributes to arterial wall cholesterol deposition, plaque development, and ASCVD endpoints. Furthermore, the additional triglyceride content in remnant particles may theoretically promote intimal inflammation and possibly plaque rupture and erosion, independently contributing to atherogenesis and ASCVD. The lipid component and pro-inflammatory properties of Lp(a) could similarly contribute directly to atherosclerotic plaque development and ASCVD. In addition, the homology with plasminogen of the defining apolipoprotein(a) moiety of Lp(a) has long been speculated to confer anti-fibrinolytic and pro-thrombotic properties that could produce more severe ASCVD outcomes independent of atherogenesis. This review explores the evolving understanding of residual lipid risk in ASCVD, practical guidance for clinicians today, recent advances in therapeutic interventions, and their implications for clinical practice, aiming to optimize lipid management beyond LDL cholesterol reduction today and in the future. Show less

Cardiovascular disease is a major cause of human morbidity and mortality. Drug strategies for the prevention of the disease are largely centered on the interaction of low-density lipoprotein receptor (LDLR) with the apolipoprotein B-100 (apoB-100) protein on low-density lipoprotein (LDL). Recently, the structure of apoB-100 on LDL was determined in the absence and presence of LDLR, using cryo-electron microscopy. A remarkable structural feature of apoB-100 is the lack of any significant tertiary structure within the C-terminal two-thirds of the protein (>3000 residues). Instead, apoB-100 forms amphipathic helices and β-sheets on the phospholipid surface of LDL, which envelops its neutral lipid core. The apoB-100 ligand binding domain for LDLR includes multiple points on a circumferential β-belt and on the N terminus. In the course of this study, we also observed several instances of structural heterogeneity in apoB-100. The various conformations may allow apoB-100 to accommodate different size lipoprotein particles and to permit recognition by other apolipoproteins or receptors. Show less

Regular physical activity can improve the blood lipid profile, yet athletes may still experience dyslipidemia. This study examined lipid profiles in Turkish endurance and strength athletes in relation to the dietary intake. Eighty-four participants, including strength athletes ( Endurance athletes had a lower body mass index (BMI), body fat (%), fat mass, waist-to-hip ratio, and waist-to-height ratio than strength athletes and non-athletes ( Endurance athletes displayed a more favorable lipid profile than strength athletes and non-athletes. Group differences in lipids likely reflect a combination of adiposity, dietary patterns, and sport-specific behaviors. Show less

Familial hypercholesterolemia (FH) is the most common monogenic lipid disorder, primarily resulting from mutations in LDLR, APOB, and PCSK9 genes. These mutations cause persistently high levels of low-density lipoprotein cholesterol (LDL-C), predisposing affected individuals to premature atherosclerotic cardiovascular disease (ASCVD). Homozygous FH (HoFH), a rare but severe form, manifests early in life with cutaneous xanthomas and accelerated coronary and aortic disease. Early diagnosis and aggressive, lifelong management are crucial, yet challenges remain, particularly when follow-up is interrupted. We report the case of a 20-year-old female diagnosed with HoFH at age 13 after presenting with xanthomas. Initial evaluation revealed mild to moderate aortic stenosis and early coronary artery involvement. Genetic testing confirmed a homozygous LDLR mutation. Despite treatment with atorvastatin and evolocumab, partial lipid control was achieved, and follow-up was disrupted during the COVID-19 pandemic. At 20 years, she presented with worsening dyspnea, paroxysmal nocturnal dyspnea, and orthopnea. Advanced imaging documented severe heart failure with an ejection fraction of 20%, significant ventricular dilation, severe mitral regurgitation, and calcified aortic stenosis. Coronary angiography demonstrated critical coronary stenoses, while subsequent adjustments in her lipid-lowering regimen, including rosuvastatin, ezetimibe, increased evolocumab dosing, and bempedoic acid, failed to stabilize her condition. Despite recommendations for surgical intervention, the patient's critical status precluded operative management, and she tragically died on the day of her scheduled follow-up. This case underscores the aggressive natural history of HoFH and the dire consequences of interrupted follow-up care. Early detection and sustained, multidisciplinary management are essential to mitigate rapid cardiovascular deterioration in HoFH patients. Consistent monitoring and prompt therapeutic adjustments remain pivotal in improving outcomes and reducing the high mortality risk associated with advanced aortic and coronary complications in these patients. Show less

The objective of this research was to investigate the association between non-traditional lipid parameters and optical coherence tomography (OCT)-characterized high-risk plaques in patients with acute myocardial infarction (AMI). This retrospective study included 249 first-episode AMI patients admitted to the First Affiliated Hospital of Lanzhou University between January 2022 and December 2024. All patients underwent OCT-guided assessment of culprit lesions before revascularization. High-risk plaques were defined by more than two of the following features: lipid arc ≥90 °, fibrous cap thickness <65 μm, or plaque rupture/thrombus. Lesions with fewer than two of these criteria were classified as non-high-risk plaques. Clinical and laboratory data were collected, and a comprehensive lipid profile was calculated, including traditional indicators [e.g., non-HDL cholesterol (non-HDL-C)] and non-traditional ratios [e.g., apolipoprotein B/A1 ratio (ApoB/A1)]. Spearman correlation was used to assess relationships between lipid parameters and high-risk plaques. After excluding collinear variables, logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed. Model discrimination and clinical value were evaluated using receiver operating characteristic (ROC) curves, the DeLong test, integrated discrimination improvement (IDI), net reclassification index (NRI), and decision curve analysis (DCA). Among 249 AMI patients, 137 (55.0%) exhibited OCT-characterized high-risk plaques. These patients were more often male (89.8%) and presented with STEMI (84.7%). They had elevated levels of myoglobin, LDL-C, non-HDL-C, ApoB, ApoB/A1, remnant lipoprotein cholesterol (RLP-C), non-HDL-C/HDL-C ratio (NHHR), and TC/HDL-C (all Both the non-traditional ApoB/A1 ratio and the traditional lipid marker non-HDL-C were independently and linearly associated with OCT-characterized high-risk plaques in AMI. Their combined assessment enhanced the identification of high-risk plaques morphology. Show less

Rapid platelet inhibition is essential for effective management during emergency percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). However, the oral dosage form of clopidogrel (CLP) commonly used in clinical practice shows a delayed onset due to gastrointestinal absorption, first-pass metabolism, and the requirement for hepatic cytochrome P450 (CYP450)-mediated bioactivation, which limits its applications in urgent scenarios and complicating post-PCI bleeding management. To address these challenges, we developed an intravenous micellar formulation (CLP/PM) using FDA-approved mPEG-PLA copolymers to promote rapid hepatic exposure and metabolic activation. By tuning the PLA chain length, micellar core density and PEG conformation were modulated, thereby influencing protein corona (PC) formation and liver-affinity interactions. Proteomic profiling revealed that micelles with intermediate PLA length selectively recruited liver-affinity apolipoproteins (ApoM, ApoH, ApoA1, and ApoB), which are known ligands of LDLR and SR-BI, while minimizing adsorption of inflammatory and opsonization proteins. The optimized CLP/PM (3.9 k) exhibited a hepatotropic-like PC that was associated with hepatocyte-enriched uptake in primary liver cell analyses. In vivo biodistribution showed rapid liver-level signal, and pharmacokinetic studies supported enhanced CYP450-mediated activation, achieving a higher C Show less

To analyze the correlation between lipid levels and the severity of polycystic ovary syndrome (PCOS) and its predictive value for pregnancy outcome. This retrospective study included 275 PCOS patients treated with ovulation induction therapy and 234 healthy controls (used only for baseline comparisons). Lipid levels were correlated with disease phenotype and sex hormones using Spearman/Pearson coefficients. Binary logistic regression and ROC curves assessed the predictive value of lipid levels for pregnancy failure. There were statistically significant differences between the two groups in glycemic indexes (fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR)) and sex hormone indexes (testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), anti-Müllerian hormone (AMH)). The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) were significantly elevated in patients with PCOS and were closely correlated with the severity of the disease. In addition, these four lipid parameters were significantly positively correlated with T, LH, FSH, and AMH, and significantly negatively correlated with E2. Elevated levels of T, LH, TG, LDL-C, and Apo B were independent risk factors for pregnancy failure after ovulation induction treatment. TG assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.861 (sensitivity 75.61%, specificity 85.53%); LDL-C assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.868 (sensitivity 75.61%, specificity 83.55%); and Apo B assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.836 (sensitivity 74.80%, specificity 86.84%). Lipid levels were significantly correlated with the severity of disease in PCOS patients, and TG, LDL-C, and Apo B levels assisted in predicting the occurrence of pregnancy failure after ovulation induction therapy. Show less

The genetic and phenotypic spectrum of homozygous familial hypercholesterolemia (HoFH) in Han Chinese populations remains insufficiently defined. To delineate the nationwide genetic and clinical features of HoFH in Taiwan, including true HoFH, double heterozygous FH (HeFH), and compound HeFH. Patients with clinically diagnosed probable or definite FH enrolled in the Taiwan FH Registry who underwent genetic testing between 2006 and 2025 were analyzed. A comprehensive workflow integrating microarray assay, mass spectrometry, targeted next-generation sequencing, and multiplex ligation-dependent probe amplification was implemented. Variants were classified using American College of Medical Genetics and Genomics guidelines. Of 1479 screened individuals, 63 were genetically confirmed to have HoFH (mean age, 32.8 ± 22.7 years), including 28.6% with atherosclerotic vascular disease. The cohort comprised 14 true HoFH (including homozygous APOB variants), 6 double HeFH, and 43 compound HeFH. The highest documented low-density lipoprotein cholesterol (LDL-C) levels were 357.3 ± 123.5 mg/dL in true HoFH, 347.3 ± 39.2 mg/dL in double HeFH, and 443.5 ± 170.9 mg/dL in compound HeFH. The most frequent genotypes were LDLR [IVS2+4A>T];[IVS2+4A>T] in true HoFH, [APOB p.R3527W];[LDLR IVS2+4A>T] and [APOB p.R3527W];[LDLR p.D90N] in double HeFH, and LDLR [p.D90N];[p.C329Y] in compound HeFH. Patients with double HeFH had lower LDL-C levels and fewer xanthomas than those with LDLR homozygosity or compound mutations, while individuals with homozygous LDLR exon deletions/duplications had the highest LDL-C levels. This nationwide study provides the first comprehensive genetic and clinical characterization of HoFH in Taiwan. Our findings highlight the importance of precise genetic diagnosis and early detection strategies in improving outcomes for this high-risk population. Show less

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by triglyceride accumulation and insulin resistance. Currently, weight loss remains the primary strategy for reducing liver fat. High-protein diets (HPDs) may improve metabolism, lower body weight, and reduce hepatic fat; however, the effects of specific protein sources are largely unknown. This study examines the effects of HPDs from animal and plant protein sources, separately and in combination, on hepatic steatosis and MASLD-related metabolic pathways. Obese fa/fa Zucker male rats received HPDs (35% kcal from protein) containing egg white, plant (soy+pea protein, 1:1), mixed (egg white+soy+pea protein, 2:1:1), or casein (HPcasein) as the protein sources, or a normal protein diet (15% kcal from protein) containing casein, for 8 weeks. HPplant and HPmixed diets increased body weight by 1.2-fold versus HPcasein. HPDs containing egg white, plant or mixed protein sources reduced the liver-body weight ratio by ∼30% and liver triglycerides by ∼50% compared to the casein diets. These changes were linked to smaller lipid droplets, less fibrosis, and decreased lipid peroxidation in liver. HPDs containing egg white, plant or mixed protein increased markers of VLDL synthesis (ApoB-100, MTP) via ChREBP. These diets also lowered HOMA-IR, and reduced HMGCS2 (ketogenesis marker). In conclusion, HPDs containing egg white or plant proteins reduced hepatic steatosis and indices of insulin resistance, unconnected to body weight. Determining the effects of specific protein sources in HPDs is an important consideration for further research on MASLD management. Show less

In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs. Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibited comparable HFpEF susceptibility regardless of genotype, developing hallmark phenotypes including diastolic dysfunction (E/E'), myocardial hypertrophy (heart weight/tibia length), cardiac fibrosis, and hepatic steatosis. Particularly, due to the reduced ejection fraction in KO mice, combined with HFD/L-NAME, the HF phenotype was ultimately manifested as impaired diastolic function and slightly reduced ejection fraction (with the characteristics of HFpEF and HFmrEF). Mechanistically, KO-HF females displayed significant estrogen axis disruption (plasma estradiol and the expression of ERα, ERβ, ESRRA, and PELP1 expression). OVX in WT females validated the importance of estrogen for HFpEF resistance. Transcriptomic profiling identified convergent targets across cardiac (ITGAD, ITGAM, FGA, and FGB) and hepatic tissues (APOA1 and APOB), revealing miR-30a-5p's orchestration of extracellular matrix remodeling (via ITGAD/ITGAM mechanotransduction),fibrinogen-mediated microvascular homeostasis, and APOB-driven metabolic dysregulation. Notably, OE intervention failed to mitigate OVX-induced cardiac/hepatic pathology, implicating estrogen-dependent miR-30a-5p functionality. These findings establish miR-30a-5p as a crucial sex-specific regulator of HF (mainly HFpEF), operating through estrogen signaling to balance cardiac compliance and metabolic adaptation. Show less