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Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people's physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is a lack of comprehensive analysis of the underlying mechanisms. This study used fully nutritious brown rice as raw material, and after germination under various stress conditions, it significantly increased the levels of gamma aminobutyric acid (GABA, four carbon non protein amino acid), resistant starch, flavonoids, and other components that regulate metabolic diseases. Using rats as experimental subjects, a model of hyperlipidemia and hyperglycemia was constructed, with rice consumption as the control. The experimental period was 8 weeks. Research has found that feeding sprouted brown rice can significantly improve the accumulation of white fat in the liver caused by a high-fat diet, significantly reduce TC, TG, LDL-C, apoB, HL, LPL, and LCAT, significantly increase HDL-C and apoA1, and significantly reduce the levels of inflammatory factors IL-6 and TNF-α. Therefore, consuming sprouted brown rice can reduce the risk of hyperlipidemia, inflammation, and tumor occurrence by promoting fat breakdown, and can also increase the abundance of metabolic-promoting microorganisms (especially Euryarchaeota and Lactobacillus) in the intestine, improving the entire metabolic ecological network of rats. Show less

Obesity is a global health challenge that can lead to various complications, such as metabolic syndrome, diabetes mellitus, and cardiovascular diseases. Heat shock proteins are evolutionarily conserved chaperones that help maintain cellular protein homeostasis. Their expression is dysregulated in various chronic diseases, including diabetes mellitus and hyperlipidemia, and they also regulate inflammatory processes. Therefore, the present study aimed to investigate the effects of a small heat shock protein, HSPB1, on the comorbidities and complications of obesity in a transgenic mouse model. Male and female human apolipoprotein B-100 (APOB) transgenic mice fed with a high-fat diet (HFD) from months 3-10 of age were used as a model of metabolic syndrome (MetS). To study whether HSPB1 influences the development of MetS, APOB animals were crossed with HSPB1-overexpressing mice. Age and sex-matched wild-type and human HSPB1-overexpressing mice were used as controls. Changes in cardiac morphology and function were assessed by transthoracic echocardiography at month 9. At month 10, serum triglyceride and cholesterol concentrations were determined by enzymatic colorimetric assays. Pathological changes in the liver were studied on hematoxylin-eosin-stained sections. Expression levels of genes involved in inflammation and metabolism were measured by quantitative real-time polymerase chain reaction in the liver, left ventricle, and visceral white adipose tissue (vWAT). The body weight and serum LDL-cholesterol levels were significantly higher in the APOB animals than in the wild-type mice in both sexes. Notably, HSPB1 overexpression further increased weight gain in female APOB animals. Conversely, in APOB males, HSPB1 overexpression decreased LDL-cholesterol levels without significantly affecting body weight. Furthermore, in APOB females, HSPB1 overexpression elevated Fgf-21 expression in the vWAT, restored Lpl levels, and reduced the expression of several cytokines in the liver. APOB males developed left ventricular hypertrophy (LVH) with diastolic dysfunction. HSPB1 overexpression induced LVH without cardiac dysfunction in the wild-type animals. Both sexes of APOB animals developed MetS. APOB males presented LVH with preserved ejection fraction (EF); however, APOB females showed enlarged left ventricular end-systolic volume (LVESV). In APOB animals, HSPB1 overexpression exerted a sex-dependent influence on obesity-related alterations, including weight gain, hypercholesterolemia, and hepatic and vWAT gene expression. Show less

Familial hypercholesterolaemia (FH) is a hereditary disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels, substantially increasing the risk of atherosclerotic cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) targeting therapies, including monoclonal antibodies and small interfering RNA (siRNA) agents, have emerged as effective lipid lowering therapies. To assess the efficacy and safety of PCSK9-targeting therapy on lipid biomarkers and adverse events in patients with FH, compared with placebo on the background of standard lipid-lowering therapy. A systematic review and meta-analysis were conducted, incorporating data from 23 randomised controlled trials involving adult and paediatric FH patients treated with PCSK9 inhibitors (PCSK9i) or siRNA, including alirocumab, bococizumab, evolocumab, tafolecimab and inclisiran. Eligible studies reported changes in LDL-C, apolipoprotein B (ApoB), lipoprotein a (Lp(a)), triglycerides (TGL) and adverse effects. Pooled mean differences (MDs) and ORs with 95% CIs were calculated using random-effects models, and heterogeneity was assessed with I² statistic. This meta-analysis was registered on PROSPERO (CRD42025631510). A total of 4282 patients were included. PCSK9-targeting therapies significantly reduced LDL-C levels compared with control therapies (MD=-46.64%; 95% CI -50.77% to -42.52%; p<0.00001) and TGL (MD=-15.18%; 95% CI -19.34% to -11.03%; p<0.00001). Significant reductions were also observed for ApoB (MD=-34.94%; 95% CI -40.89% to -28.99%; p<0.00001) and Lp(a) (MD=-22.7%; 95% CI -25.95% to -19.44%; p<0.00001). LDL-C, TGL and ApoB reduction were more significant in heterozygous FH patients than in homozygous patients. The safety profile of these therapies was favourable, with adverse event rates comparable to those of the controls. PCSK9i and Inclisiran demonstrate significant and sustained reductions in LDL-C, ApoB, Lp(a) and TGL in FH patients, especially in heterozygous FH patients. These agents are generally well-tolerated and represent effective treatment options for FH patients inadequately controlled by standard lipid-lowering therapies. Show less

Elevated lipoprotein(a) [Lp(a)] levels increase cardiovascular (CV) risk. Lp(a) contains oxidized phospholipids that may promote lipid oxidation more than other lipoproteins. The highly unsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) has multiple double bonds that can trap free radicals in resonance structures. Purified ethyl-EPA reduced CV events in high-risk patients with elevated Lp(a) despite Lp(a)-associated risk elevation. Since Lp(a) is enriched in oxidized lipids, we hypothesized that Lp(a)-enriched plasma undergoes more rapid oxidation than other apolipoprotein B (ApoB)-containing particles and that EPA limits oxidation of Lp(a)-enriched plasma more effectively than less-unsaturated fatty acids or other lipid-lowering treatments. This property could limit the cellular stress responses in endothelial cells (ECs). Lp(a) was enriched to >50% total ApoB content to resemble an Lp(a)-associated 'high-risk' phenotype and compared with matching levels of small-dense LDL (sdLDL) and very-low-density lipoprotein by isopycnic centrifugation. Samples were then incubated with EPA (50 µM) or equivolume vehicle at 37°C for 30 min. Oxidation was initiated with copper sulfate and monitored by malondialdehyde formation. We also subjected EPA to oxidation before measuring its antioxidant activity when compared with other long chain, less saturated fatty acids and lipid-lowering agents. Human umbilical vein ECs (HUVECs) were incubated with Lp(a)-enriched plasma following oxidation in the absence and presence of EPA. Cell lysate samples were then analysed by global liquid chromatography-mass spectroscopy (LC/MS)-based proteomics for significant changes in protein expression (>1-fold). Lp(a)-enriched plasma contained the highest baseline oxidized lipid (P < 0.05) and underwent the most rapid oxidation. EPA, but neither the less-unsaturated fatty acids nor lipid agents attenuated oxidation of each fraction through 4 h (P < 0.01). Oxidized EPA had diminished antioxidant capacity corresponding to the extent of oxidation. Attenuation of Lp(a) oxidation with EPA also mitigated pro-inflammatory and cellular stress response changes in protein expression. Lp(a)-enriched plasma underwent more rapid oxidation than other ApoB-containing lipoproteins and promoted inflammatory changes in EC protein expression, a process attenuated by EPA. This action may contribute to reduced CV risk by EPA in those with elevated Lp(a) levels. Show less

Apolipoprotein B (apoB) is the primary structural protein in low-density lipoprotein (LDL) and plays a crucial role in atherogenesis. The Framingham Risk Score (FRS) is a widely used tool for assessing cardiovascular disease (CVD) risk. However, the correlation between apoB and FRS in Iraqi individuals remains underexplored. This study aims to evaluate the association between serum apoB levels and FRS, establishing its potential utility as a predictive biomarker for coronary artery disease (CAD) risk. A cross-sectional study was conducted on 201 individuals aged ≥30 years attending a clinical laboratory in Baghdad between November 2022 and October 2023. Serum apoB and lipid profiles were measured, and FRS was calculated for all participants. Correlation analysis between apoB and FRS was performed using Spearman's test, while group comparisons were conducted The median age of participants was 48 years, with males constituting 51.2% of the cohort. Median apoB and FRS values were 130 mg/dL and 4, respectively. A strong positive correlation was observed between serum apoB and FRS ( These findings suggest that apoB may serve as a reliable biomarker for CAD risk assessment in the Iraqi population, where its predictive value has been underexplored. The identified cutoff value (97.75 mg/dL) highlights its potential role in refining risk stratification beyond traditional lipid markers. Further prospective studies are needed to validate these findings and assess their clinical impact. Show less

Familial hypercholesterolemia (FH) is a co-dominantly inherited condition that leads to enhanced risk of atherosclerotic cardiovascular disease (ASCVD). The Montreal FH Score (MFHS), Combined FH Score (CFHS), and FH Risk Score (FHRS) are strongly associated with ASCVD events in patients with heterozygous FH (HeFH). In this study, the association between these risk scores and prevalent ASCVD was evaluated among Australian patients with HeFH. We collected clinical data from 655 adult patients with genetically confirmed HeFH (87% with LDLR, 11% with APOB, and 2% with PCSK9 or APOE p.Leu167del variants). Logistic regression was used to assess the association between risk scores and prevalence of ASCVD. Receiver operating characteristic curve analysis was used to evaluate the discriminatory ability of the risk scores. We identified 153 patients with a history of ASCVD events. A 1-unit increase in the MFHS, CFHS, and FHRS was associated with 16%, 18%, and 14% increase in the odds of ASCVD, respectively. Patients with high (greater than the median) MFHS (≥ 25), CFHS (≥ 26), and FHRS (≥ 31) had 9.7-fold, 9.1-fold, and 13.4-fold greater odds of ASCVD compared with those with low scores. The area under the receiver operating characteristic curve for MFHS, CFHS, and FHRS were 0.808 (95% confidence interval [CI], 0.772-0.844), 0.821 (95% CI, 0.785-0.856), and 0.818 (95% CI, 0.782-0.854), respectively, indicating excellent discriminatory ability, with the area under the receiver operating characteristic curve for CFHS being significantly higher than for the MFHS (P = 0.014). The MFHS, CFHS, and FHRS were strongly associated with an increase in the prevalence of ASCVD, with excellent discriminatory ability in identifying ASCVD in Australian patients with HeFH. Show less

Memory impairment is frequent among alcohol use disorder (AUD) patients, and we lack specific biomarkers to detect it. Certain apolipoproteins were linked to cognition, and carrying the APOE4 gene is a vulnerability factor to memory impairment in AUD patients. We explored memory deficits in alcohol-dependent male mice and humans versus controls, and their relationship to Apolipoprotein AI (APOAI), apolipoprotein B (APOB), and apolipoprotein E (APOE) plasma levels. Male C57BL/6J mice underwent voluntary alcohol drinking (two-bottle choice, 2BC) and chronic intermittent ethanol vapor exposure (CIE) as a model of alcohol dependence; memory was assessed by the Object Location Test (OLT) and Novel Object Recognition Test (NORT). Additionally, male AUD-diagnosed patients were recruited in Spain during an alcohol dishabituation program and assessed by the Wechsler Memory Scale-IV (WMS-IV). Plasma APOAI, APOB, and APOE levels were checked in mice and humans by ELISA kits and Luminex immunoassay technology. APOAI immunolabeling was quantified in mouse brain in early withdrawal and following alcohol consumption. CIE-2BC mice (n = 8) escalated alcohol consumption compared to Air-2BC controls (n = 11) and showed deficits in spatial memory (OLT) and recognition memory (NORT) while AUD patients (n = 12) showed deficits in verbal and visual memory (WMS-IV) versus controls (n = 16). Higher plasma levels of APOAI were detected in CIE-2BC mice and AUD patients, with no differences in APOB and APOE in animals and humans. Significant negative correlations were found between levels of APOAI, APOB, and APOE and memory function tests/scales in the entire sample, with APOAI showing consistent results in both animals and humans. APOAI immunoreactivity was detected in the mice subfornical organ, but the signal did not differ between experimental groups. Both CIE-2BC mice and AUD patients exhibited elevated plasma levels of APOAI during early abstinence. APOAI correlated with poorer memory performance in both species, suggesting a potential role for this apolipoprotein in the context of alcohol-induced cognitive impairment. Show less

Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage disorder involving bile acid biosynthesis. Reduced mitochondrial cytochrome P450 enzyme activity leads to abnormal lipid accumulation in various tissues, especially tendons, lenses, and the central and peripheral nervous systems. This condition manifests with systemic symptoms such as neurological disorders, atherosclerosis, tendon xanthomas, and cataracts. Cerebrotendinous xanthomatosis typically presents in individuals with homozygous or compound heterozygous mutations in the CYP27A1 gene because of its autosomal recessive inheritance pattern. However, the phenotypic expression in heterozygous carriers remains uncertain. We report a 53-year-old Japanese man who was clinically diagnosed with familial hypercholesterolemia. He presented with marked Achilles tendon xanthomas and refractory hyper-low-density-lipoprotein cholesterolemia. Initiation of intensified lipid-lowering therapy, including inclisiran, resulted in improvement of hyper-low-density-lipoprotein cholesterolemia. Genetic testing revealed heterozygous mutations in CYP27A1 (p.Arg405Gln) and apolipoprotein B (APOB) (p.Pro955Ser). He had no neurological symptoms, cataracts, or other features suggestive of cerebrotendinous xanthomatosis without Achilles tendon xanthomas. This case highlights a rare presentation of a potential CYP27A1 heterozygous mutation-related phenotype. The APOB (p.Pro955Ser) variant is associated with reduced low-density-lipoprotein receptor activity, contributing to hyper-low-density-lipoprotein cholesterolemia and Achilles tendon xanthomas. However, this patient's Achilles tendon xanthoma was thicker than those reported in previous cases with APOB (p.Pro955Ser) gene mutations, suggesting a potential contribution from the CYP27A1 mutation. Although the patient did not exhibit elevated serum cholestanol levels or other cerebrotendinous xanthomatosis features, the marked Achilles tendon thickening raises the possibility that the combination of a heterozygous CYP27A1 gene mutation and an APOB gene mutation contributed to the condition. Show less

Despite significant evidence of a genetic contribution to strabismus, precise genetic mechanisms have not been identified. There are distinct population differences in the prevalence of strabismus and its subtypes. This study aimed to explore the genetic contributions to strabismus in different ancestral groups. Case-control. The Genome-wide association study of common variants (minor allele frequency >1%) and rare variant association study at the gene level for strabismus. Individual single nucleotide polymorphisms (SNPs) significantly associated with strabismus and genes with significant burden of rare variants in strabismus. Genome-wide association study identified one locus with 3 significant SNPs (rs2247113, rs2667037, and rs2715926) in intron 1 of Genetic associations with strabismus differed between ancestry groups, although genes in similar pathways, such as synaptic signaling and structural muscle proteins, were found in multiple groups. This highlights the importance of including diverse populations in studies of genetic associations and suggests that multiple pathways may lead to strabismus in different population groups. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Show less

Lipoprotein kinetics are a crucial factor in understanding lipoprotein metabolism because a prolonged time in circulation can contribute to the atherogenic character of B-lps (ApoB-containing lipoproteins). We developed a genetically encoded B-Lp reporter, LipoTimer, in which the zebrafish endogenous By quantifying the red population of ApoB-Dendra2 over time, we found that B-lp turnover in wild-type larvae becomes faster as development proceeds. Mutants with impaired B-lp uptake or lipolysis present with increased B-lp levels and half-life. In contrast, mutants with impaired B-lp triglyceride loading display slightly fewer and smaller B-lps, which have a significantly shorter B-lp half-life. Furthermore, we showed that chronic high-cholesterol feeding is associated with a longer B-lp half-life in wild-type juveniles but does not lead to changes in B-lp half-life in lipolysis-deficient In conclusion, the new LipoTimer reporter allows for direct in vivo examination of B-lp kinetics, which can be used to better understand the role of lipoprotein modifier genes and environmental factors (eg, diet) on B-lp lifetime. Show less

Patients born with congenital porto-systemic shunts have been shown to have a high risk of benign and malignant liver tumors in otherwise healthy livers. This study aimed to evaluate the genetic landscape of liver tumors in patients with congenital porto-systemic shunts (CPSS) and correlate genotype with histological findings. Nodules from patients with CPSS and sporadic pediatric focal nodular hyperplasia (FNH) or FNH-like nodules were evaluated histologically and sequenced for a panel of 50 genes using next-generation sequencing. Thirty-eight nodules from 17 patients with CPSS were histologically classified as hepatoblastomas ( CPSS is strongly associated with nodules containing variants in Show less

The formation and progression of atherosclerotic plaques occur through cellular dysfunction and remodeling of the extracellular matrix in the sub-endothelial space of vessels. The immunity against specific antigens is suggested to mitigate the atherosclerosis process. Primarily, studies have suggested that certain antigens, such as ox-LDL, ApoB-100, CETP, PCSK9, HSP60, MHC-II-derived peptides, and interleukins, are involved in atherosclerosis. However, recognizing the intricate interplay between immune responses and the formation of arterial plaques is essential to optimize immunization against atherosclerosis. In this review, the roles of some genes were presented in triggering atherosclerotic plaque events. Furthermore, some immunization approaches are presented to target these genes. The studies suggested that vaccination against the progression of atherosclerosis is an essential and effective approach to reducing the high death rate in autoimmune diseases. Show less

Type 2 diabetes mellitus (T2DM) is known to adversely impact brain health, leading to cognitive decline and brain tissue volume reduction. This study aimed to assess the damage to gray-white matter junction tissue volume (gwJTV) in T2DM patients with and without carotid artery plaques, and its association with various metabolic parameters. We conducted a cross-sectional study involving 69 T2DM patients, employing three-dimensional T1-weighted MRI scans to measure brain tissue volumes, particularly gwJTV, and analyzing blood samples for metabolic parameters. Voxel-based (VBA) and region-of-interest (ROI) analyses of gwJTV were performed to evaluate the group difference with and without carotid artery plaques and to determine correlations to metabolic biomarkers. Voxel-based and region-of-interest analyses revealed that participants with carotid plaques had lower gwJTV than those without at the specific brain area. ROI results study further demonstrated positive associations between gwJTV and metabolic parameters such as AST, ApoB, and LDL, and negative associations with C-peptide, creatinine, and hsCRP. Our findings suggest that gwJTV could be a valuable imaging biomarker for monitoring brain and vascular health in T2DM patients, particularly those affected by carotid atherosclerosis. Show less

Immune checkpoint inhibitors (ICIs) have improved the metastatic melanoma (MM) treatment. However, a significant proportion of patients show resistance to immunotherapy, and predictive biomarkers for non-responders or high-risk recurring patients are currently lacking. Recent studies have shown that tumor-related metabolic fingerprints can be useful in predicting prognosis and response to therapy in various cancer types. Our study aimed to identify serum-derived metabolomic signatures that could predict clinical responses in MM patients treated with ICIs. A multivariable model was used to identify distinct prognostic factors for OS. Negative factors included glucose, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B-very low-density lipoprotein (ApoB-VLDL), whereas glutamine and free HDL cholesterol emerged as positive factors. They were then used to construct a risk score model able to stratify patients in prognostic groups. Similarly, a separate predictive risk score model for PFS was developed, focusing solely on glucose and apolipoprotein A1 (ApoA1) HDL. Threefold cross validation resulted in mean concordance indices of 0.72 and 0.74 for PFS and OS, respectively. Importantly, this analysis was replicated in patients who received first-line ICIs. Interestingly, the prognostic score for OS included glutamine, glucose, and LDL (low-density lipoprotein) triglycerides, whereas only glucose negatively influenced PFS. In this subset, the concordance indices increased to 0.81 and 0.9 for PFS and OS, respectively. Our data identified glycolipid signatures as robust predictors of distinct therapeutic outcomes in MM patients treated with ICIs. These results could pave the way for novel therapeutic approaches. Show less

In vertebrates, the provision of nutrients to developing embryos varies widely, ranging from yolk-dependent strategies to highly specialized forms of placental nourishment. Vitellogenins (VTGs) are essential proteins for egg yolk formation in oviparous and lecithotrophic species. In contrast, in eutherian mammals, the loss of VTGs is associated with the evolution of matrotrophy (placentotrophy and lactation), where maternal nutrition via the placenta replaces the need for large yolk reserves during embryonic development. Marisora sp., a placentotrophic viviparous lizard with the most complex placenta known in reptiles, exhibits truncated vitellogenesis, resulting in the production of microlecithal eggs. This study investigated the presence of VTGs in Marisora sp. using RNA-seq from the liver and ovary at previtellogenesis and vitellogenesis stages. No corresponding annotations for VTGs were found. This absence may be associated with the placentotrophic nutrition of the embryo, suggesting modifications in lipid production and transport to the ovarian follicles. Apolipoprotein B (ApoB) and microsomal triglyceride transfer proteins (MTP) were identified, which are closely related to VTGs and could fulfill their function, especially ApoB, which is involved in yolk formation in lecithotrophic species in which VTGs are absent. The absence of VTGs in the Marisora sp. transcriptome represents a key discovery in the evolution of obligate placentotrophic viviparity in reptiles, highlighting convergent traits with mammals. Genomic studies are required to determine if changes in VTG genes prevent or modify their expression, and proteomic studies are needed to fully understand the role of other lipid transport proteins in the preovulatory ovarian follicles of these lizards. Show less

The current research work was designed to study the amylose content, total phenolic content (TPC), total flavonoid content (TFC), total anthocyanin content (TAC) and digestibility of unpolished chakhao amubi (CA) rice extract along with antioxidant, antihyperlipidemic activity. In addition, the profiling of the bioactive polyphenolic compounds present in unpolished CA rice flour was evaluated. Based on the results obtained from the in vitro antioxidant and hypolipidemic activities of all the rice extract, CA-EtOH (ethanol) was selected for in vivo study. Effect of CA-EtOH after 45 days treatment was evaluated in high-fat-high-sugar (HFHS) induced Wistar rats. The unpolished CA rice produces higher levels of TPC (346.53 mg GAE/100 g DW), TFC (634.22 mg QUE/100 G DW) and TAC (873.34 mg C-3-G/100 g DW) compared to polished rice and CA-EtOH extract showed strong antioxidant activity with the lowest IC Show less

OxPL-apoB (oxidized phospholipids [OxPL] on apoB-100), which include OxPL present on Lp(a) (lipoprotein[a]), are associated with higher cardiovascular risk. Experimental studies suggest that OxPL may influence platelet function. This observational study assessed the association of OxPL-apoB with intrinsic and on‑clopidogrel platelet reactivity and long-term cardiovascular events in patients undergoing coronary angiography with or without percutaneous coronary intervention in 2040 patients in the EXCELSIOR trial (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate). The association of OxPL-apoB to expression of CD62P, CD41, or PAC-1 levels and intrinsic and on-clopidogrel platelet reactivity to collagen and ADP was determined. The relationship of OxPL-apoB and Lp(a) to myocardial infarction-free survival and all-cause mortality at a median of 7 years was assessed using Cox regression models. Elevated levels of OxPL-apoB were associated with the severity of coronary obstruction, and higher prevalence of prior myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft surgery. No significant associations were present between OxPL-apoB and intrinsic or on-clopidogrel platelet reactivity or activation of platelet receptors. Analyzed individually in separate multivariable models, both OxPL-apoB (hazard ratio, 1.022 [95% CI, 1.005-1.040]; In patients undergoing coronary angiography with or without percutaneous coronary intervention, OxPL-apoB was not associated with intrinsic and on-clopidogrel platelet reactivity mediated by collagen or ADP. The association of OxPL-apoB and Lp(a) suggests that the accumulation of OxPL on Lp(a) may be a key determinant of long-term cardiovascular outcomes. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00457236. Show less

A key step in primary prevention is the assessment of atherosclerotic cardiovascular disease (ASCVD) risk. Risk enhancer tests are additional tools used to further improve ASCVD risk assessment over conventional risk markers. Our objective was to determine whether estimated small, dense low-density lipoprotein cholesterol (E-sdLDL-C) can improve risk assessment and serve as a new risk enhancer test. We used a prospective cohort analysis of participants in the UK Biobank study with a median (interquartile range) follow-up of 10 (6.7-12.3) years. We included 271 760 individuals who were not on lipid-lowering medication at baseline and did not have incident ASCVD. The primary study outcome was the incidence of all-cause ASCVD. E-sdLDL-C was strongly associated with ASCVD events with a hazard ratio (HR) of 1.23 (95% CI, 1.22-1.24). After multivariable adjustment for age, sex, systolic blood pressure, hypertension, type 2 diabetes, and blood pressure medications, E-sdLDL-C and ApoB (apolipoprotein B) remained the most significant lipid risk factors (HR, 1.18 [95% CI, 1.16-1.19] and 1.17 [95% CI, 1.16-1.18] per SD, respectively). After further adjustment for ApoB, the association between low-density lipoprotein cholesterol (LDL-C) with all-cause ASCVD was completely reversed with an HR of 0.84 (95% CI, 0.81-0.86), but E-sdLDL-C continued to have a significant positive association with an HR of 1.11 (95% CI, 1.08-1.13). When E-sdLDL-C was discordantly higher than either LDL-C or ApoB, the risk for ASCVD was higher (LDL-C, 31% higher; ApoB, 17% higher). When elevated E-sdLDL-C is coupled with other risk enhancer tests, there is a greater risk for developing ASCVD. In a UK Biobank cohort for primary prevention, the risk of all-cause ASCVD was better captured by E-sdLDL-C than LDL-C. It was also more predictive than LDL-C and ApoB when discordant with these 2 measures. E-sdLDL-C, which can be freely and automatically calculated from a standard lipid panel, can potentially improve ASCVD risk assessment without additional laboratory testing. Show less

Dyslipidemia remains a central contributor to residual cardiovascular risk despite the widespread use of statins. Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, has shown potential as an adjunctive lipid-lowering therapy by favorably modifying key lipid parameters. This study aimed to systematically evaluate the lipid-lowering efficacy of obicetrapib based on current evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted on PubMed, Embase, Scopus, and ClinicalTrials.gov to identify RCTs assessing the lipid-lowering effects of obicetrapib. Mean differences (MDs) with 95% CIs were calculated using a random-effects model. Nine RCTs (n = 3706) were included. Patients treated with obicetrapib exhibited significant reductions in low-density lipoprotein cholesterol (LDL-C) (MD: -36.5% [95% CI: -41.1 to -31.9]), apolipoprotein B (Apo-B) (MD: -23.8% [95% CI: -28.2 to -19.3]), non-high-density lipoprotein cholesterol (non-HDL-C) (MD: -30.9% [95% CI: -34.6 to -27.1]), and lipoprotein (a) [Lp(a)] (MD: -36.1% [95% CI: -44.4 to -27.8]) compared to placebo. High-density lipoprotein cholesterol (HDL-C) levels significantly increased (MD: 142.6% [95% CI: 128.6-156.6]). Triglyceride levels did not differ significantly (MD: 0.13% [95% CI: -7.01 to 7.26]). Moreover, combination therapy with ezetimibe led to greater reductions in LDL-C by 17.8% (95% CI: 12.05-23.6), Apo-B by 9.7% (95% CI: 5.8-13.7), and non-HDL-C by 17.5% (95% CI: 12.3-22.8), compared to monotherapy. Obicetrapib significantly improves key lipid parameters, including LDL-C, Apo-B, non-HDL-C, HDL-C, and Lp(a), with enhanced efficacy in lowering LDL-C, Apo-B, and non-HDL-C when combined with ezetimibe. These findings support its potential role in comprehensive lipid management strategies. Show less

Calcific aortic valve stenosis (CAVS) is steadily rising worldwide with no effective pharmacological agents available. Observational studies implicated dyslipidaemia as a risk factor for CAVS. Whether dyslipidaemia is causative for CAVS and the therapeutic potential of different lipid-modifying drug targets for CAVS treatment remains unclear. We appraised the relationship of genetically-proxied lipid traits and 12 lipid-modifying drug targets with CAVS risk using Mendelian randomization (MR). Genetic variants associated with lipid traits and variants in genes encoding lipid-modifying drug targets were retrieved from GLGC. Summary-level data for CAVS were obtained from the TARGET consortium and FinnGen. Validation analyses were performed using genetic instruments retrieved from liver-derived gene expression and circulation plasma levels of targets. Colocalisation and mediation analyses were performed to evaluate the robustness of our findings and explore potential mediators (i.e., lipoprotein a (Lp(a)), body mass index, apolipoprotein B (ApoB)). The MR analyses supported that total cholesterol and LDL-cholesterol level were independent causal risk factors. The drug-target MR analysis suggested that genetic mimicry of PCSK9 inhibition should reduce CAVS risk (OR = 0.63, 95% CI = 0.56-0.70), which was corroborated by colocalisation analysis. Secondary analyses supported a genetically proxied effect of liver-specific PCSK9 expression (OR = 0.94 per SD reduction in PCSK9 expression, 95% CI = 0.88-1.00) and circulating plasma levels of PCSK9 (OR = 0.86 per SD reduction in PCSK9 protein, 95% CI = 0.83-0.88) on CAVS risk. ApoB and Lp(a) mediated 55.9% and 4.5%, respectively, of the total effect of PCSK9 on CAVS risk. Multiple sensitivity analyses supported this observation. Our study supports total cholesterol, LDL-cholesterol as a causal factor for CAVS, and genetically proxied inhibition of PCSK9 may reduced its risk. Show less

To quantify international variations in lipid-lowering therapies (LLT) use among patients with coronary heart disease (CHD) and attainment of European guideline-recommended lipid goals. INTERASPIRE is an observational study (2020-23) covering 14 countries from all WHO regions. Patients (18-79 years) hospitalized in the preceding 6-36 months with CHD were invited for standardized interviews and examination, with central laboratory analyses for low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and apolipoprotein B (apoB). Valid lipid data meeting quality control standards were available from 13 countries. Lipid goals followed the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology: LDL-C < 1.4 mmol/L, non-HDL-C < 2.2 mmol/L, and apoB <65 mg/dL.Among 4061 patients (78.8% male, mean age 60.3 years), between index event and interview, 66.3% had no change in treatment intensity. LLT use at interview was largely statin monotherapy: 49.6% high-intensity (inter-country range 5.3%-77.3%) and 24.1% low/moderate-intensity (inter-country range 5.1%-70.1%). Otherwise, 12.2% (inter-country range 0.2%-41.1%) were on combination therapy, and 12.7% on no LLT (inter-country range 3.5%-36.7%). Goal attainment for LDL-C was 17.5%. Corresponding non-HDL-C and apoB goals were achieved by 29.9% and 29.2%, respectively. Higher-income countries (defined by the World Bank's 2024-25 classification of income levels) did better in goal attainment than lower-middle-income countries. In this international study, contemporary lipid goals were not achieved in most CHD patients, with lower-middle-income countries having the worst goal attainment. Contributory factors include absence of any LLT use, low use of combinations and a failure to up-titrate LLT to achieve guideline targets. Show less

The role of lipid markers in acute coronary syndrome remains incompletely understood, particularly for novel indices such as the Castelli risk indices (CRI-I, CRI-II) and cholesterol index (CHOINDEX). This study aims to elucidate the relationship between novel lipid markers and plaque rupture. In this single-center retrospective study, 649 patients with acute coronary syndrome undergoing optical coherence tomography were stratified into plaque rupture (n = 130) and non-rupture (n = 519) groups. Lipid indices included the following: CRI-I - total cholesterol/high-density lipoprotein cholesterol (HDL-C), CRI-II - low-density lipoprotein cholesterol (LDL-C)/HDL-C, and CHOINDEX - LDL-C/HDL-C. Multivariable logistic regression identified independent predictors of plaque rupture. Model performance was assessed using area under the curve and integrated discrimination improvement. The plaque rupture group had higher proportions of males (89.2% vs. 80%; P = 0.01) and smokers (57.7% vs. 44.9%; P = 0.009), with elevated LDL-C mean 3.14 vs. 2.83 mmol/l), apolipoprotein B (APOB; 1.03 vs. 0.85 g/l), CRI-I (4.75 vs. 3.91), CRI-II (3.11 vs. 2.45), and CHOINDEX (1.97 vs. 1.65; all P <0.01). Multivariable analysis identified CRI-I (odds ratio [OR], 1.57), CRI-II (OR, 2.09), CHOINDEX (OR, 0.40), and APOB (OR, 5.50) as independent predictors. The combined model (traditional factors + novel indices) showed superior discrimination (area under the curve = 0.775 vs. 0.622; integrated discrimination improvement = 0.059; P <0.001). The combined assessment of CRI-II, CRI-I, CHOINDEX, and APOB, in conjunction with traditional cardiovascular risk factors, exhibits robust diagnostic efficacy for plaque rupture. Show less

This umbrella review aims to synthesize evidence from previously conducted meta-analyses and review articles to assess the effects of bempedoic acid on lipid profile and cardiovascular events. While adhering to the Preferred Reporting Items for Overviews of Reviews guidelines, PubMed, Google Scholar, Web of Science, and Scopus were searched from the database inception to June 2024 to identify relevant articles. The outcomes were total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, triglyceride (TAG), apolipoprotein B (APOB), high-sensitivity CRP (hs-CRP), major cardiovascular events (MACE), cardiovascular mortality, and myocardial infarction (MI). A corrected covered area (CCA) assessment was performed to determine overlap among reviews. Each included review was assessed for its quality and rigor via the AMSTAR-2 tool. From 18,297 articles identified during the literature search, 18 meta-analyses were included. A significant overlap was noted across studies with a corrected cover area of 44.4%. Bempedoic acid's effects on cardiovascular outcomes and lipid levels have been extensively studied. For cardiovascular mortality, the evidence is mixed: Goyal et al. Our findings show that bempedoic acid significantly reduces the risk of MACE, nonfatal MI, coronary and noncoronary revascularization, and hospitalizations for unstable angina. While results on cardiovascular mortality are mixed, suggesting a need for further study, bempedoic acid proves to be an effective treatment for improving lipid profiles and reducing cardiovascular events, especially in patients who cannot tolerate statins. It presents a valuable option for cardiovascular risk management, potentially enhancing patient outcomes and quality of life. Further research is needed to assess its long-term benefits and broader applicability. Show less

Obesity and dysregulated cytokine levels are prevalent in schizophrenia patients undergoing antipsychotic treatment. While cytokines are implicated in obesity, their relationship with psychopathology in schizophrenia remains underexplored. This study investigated associations between body mass index (BMI), cytokine levels, and clinical symptoms in chronic schizophrenia patients. In this cross-sectional study,201chronic schizophrenia patients (Chinese Han population) were stratified into high BMI (BMI≥25kg/m A significant negative correlation was observed between BMI and IL-2( Higher BMI in chronic schizophrenia is associated with reduced IL-2 levels, attenuated negative symptoms, and adverse lipid profiles. TNF-α may modulate psychopathology severity. These findings highlight complex interactions between metabolic dysregulation, immune markers, and clinical manifestations in schizophrenia. Show less