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Seasonal variation in cardiovascular disease (CVD) is well documented. Data on seasonal fluctuations in cardiovascular risk markers are relatively sparse but may be relevant for CVD risk classification and treatment. We aimed to quantify the presence, magnitude, and timing of seasonality across various cardiovascular risk markers in patients referred to coronary angiography. In this retrospective, cross-sectional study, we analysed cardiovascular risk markers in 3316 patients referred to coronary angiography between July 1997 and January 2000 from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Seasonal patterns were assessed using robust cosinor regressions, while correcting for age and sex. For each cardiovascular risk marker, we evaluated seasonality, peak date and magnitude (difference between peak and nadir) of seasonal fluctuations. Accordingly, we analysed 24 different cardiovascular risk markers and corrected for the false discovery rate (FDR). Overall, 16 cardiovascular risk markers showed significant seasonal dependency, of which the following had Cohen's d higher than 0.2 (peak-nadir difference): 25-hydroxyvitamin D (10.28 ng/mL), LDL cholesterol (15.36 mg/dL), HbA1c (0.31%), Omega-3 Index (0.45%), HDL (3.18 mg/dL), HOMA Index (0.54), calcium (0.03 mmol/L), and ApoB (5.6 mg/dL). Timing of peaks varied starkly. The seasonality in cardiovascular risk markers of patients referred to coronary angiography indicates that diagnostic and therapeutic thresholds for these markers should consider the date of assessment. Diverse seasonality timings suggest that the underlying mechanisms for seasonal fluctuations are likely multifactorial. Further research should evaluate the individual and environmental factors that may cause these seasonal fluctuations. Show less

This study aimed to evaluate the association between the LDL-c/ApoB ratio (LAR) and the prevalence of gallstones in regional Chinese adults. We conducted a cross-sectional study involving patients with gallstones who underwent surgical treatment at our hospital from March 2021 to September 2023, as well as e-cases from our medical check-up center during the same period. Participants were divided into gallstone and non-gallstone groups. Data on routine blood and biochemical tests, hypertension, and diabetes mellitus history were collected. The differences between the two groups were analyzed using the chi-square test or Kruskal-Wallis rank sum test. Logistic regression analysis, subgroup analysis, and propensity-matched analysis were performed to assess the relationship between LAR and the prevalence of gallstones. The study included 801 participants aged over 18 years, of whom 259 had gallstones. After adjusting for relevant confounders, LAR was found to be negatively associated with gallstone prevalence (OR = 0.67, 95% CI: 0.48, 0.95). Propensity-matched analyses confirmed that an elevated LAR remained negatively associated with gallstone prevalence (OR = 0.65, 95% CI: 0.43, 0.98). The dose-response curve indicated a linear negative correlation between LAR and gallstone prevalence. LAR is negatively associated with the prevalence of gallstones. Although a causal relationship cannot be established, these findings may provide preliminary insights for gallstone prediction in regional Chinese adult populations. Show less

Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL cholesterol (LDL-C), and reduces apolipoprotein B (apoB) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia. We conducted a coronary computed tomography angiography (CCTA) study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen vs. placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence or high risk for cardiovascular disease, and non-calcified plaque on baseline CCTA. The primary endpoint was percent change from baseline to 12 months in non-calcified plaque volume (NCPV). Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (IQR 56-70); 31% were women, and 97% received lipid-lowering therapy. Median baseline triglycerides were 249 mg/dL (IQR 197-331), and remnant cholesterol was 53 mg/dL (IQR 38-76). Median baseline NCPV was 125.3 mm Despite substantial triglyceride and remnant cholesterol lowering, treatment with olezarsen for 12 months on top of standard-of-care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia did not affect noncalcified coronary plaque volume. Show less

Cardiovascular and renal diseases exhibit a close bidirectional interaction, which often leads to the development of cardio-renal syndrome (CRS)-a clinical condition in which cardiac dysfunction further aggravates renal injury. Type I CRS is characterized by acute kidney injury secondary to acute heart failure, and this sub-type is closely related to elevated morbidity and mortality in patients with coronary artery disease (CAD). Despite the availability of traditional biomarkers, there is an unmet need for more sensitive indicators to identify high-risk patients for Type I CRS in CAD patients. The apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio has emerged as a promising predictor of cardiovascular risk, yet its role in CRS remains unclear. This study aimed to evaluate the association between the ApoB/ApoA1 ratio and Type I CRS in patients with CAD, and to assess its value as a biomarker for identifying high-risk patients. A retrospective cohort study was carried out on 269 CAD patients complicated with heart failure who were hospitalized in our hospital from 2022 to 2024. According to the estimated glomerular filtration rate (eGFR) results, the enrolled patients were divided into two subgroups: the simple heart failure (SHF) group and the type I CRS group. Data on demographics, clinical history, biochemical measurements, echocardiographic and coronary angiography assessments, and renal function were collected. A multivariable logistic regression model was used to assess the association between the ApoB/ApoA1 ratio and CRS, adjusting for potential confounders. Correlation analyses were performed to explore the relationships between key variables and the occurrence of type I CRS. A multivariable logistic regression model was used to assess the association between the ApoB/ApoA1 ratio and CRS. Furthermore, a receiver operating characteristic (ROC) curve was constructed to evaluate the predictive accuracy of the ApoB/ApoA1 ratio for type I CRS. A total of 269 patients were enrolled. Significant differences were observed between the simple heart failure (SHF) group and the CRS group in terms of age, history of diabetes mellitus, levels of triglycerides (TG), apolipoprotein A1 (apo-A1), apolipoprotein B (apo-B), ApoB/ApoA1 ratio, and serum creatinine (Scr). Patients in the CRS group were older, had a higher proportion of diabetes mellitus, higher levels of TG, apo-B, and Scr, a higher ApoB/ApoA1 ratio, but lower levels of apo-A1 compared to the SHF group. Multivariable logistic regression analysis identified age and the ApoB/ApoA1 ratio as independent risk factors for CRS. The receiver operating characteristic (ROC) curve analysis showed that the ApoB/ApoA1 ratio had a moderate level of predictive accuracy for Type I CRS, with an area under the curve (AUC) of 0.782. The ApoB/ApoA1 ratio is moderately associated with the risk of developing Type I CRS in patients with CAD. This ratio could serve as a clinically relevant biomarker for early identification of in-hospital Type I CRS risk in CAD patients with acute heart failure, potentially aiding in the implementation of early and targeted interventions to improve patient outcomes. Show less

Lipid Nanoparticles (LDE) have been used as a drug delivery vehicle to treat various diseases. LDEs resemble the structure of human low-density lipoprotein (LDL), but lack apoliprotein B (apo-B). The aim of this study was to determine whether changes in the proportion of unesterified cholesterol (UC) or triacylglycerols (TG) affect the physical stability of LDE in aqueous solutions over a six-month observation period, as analysed by Ultra Small-angle X-ray Scattering (USAXS), Dynamic Light Scattering (DLS) and zeta potential measurements. It was shown that variations in UC or TG content in the initial lipid mixture did not alter the size of the resulting LDE nanoparticles, which remained within the 30-35 nm range. This particle size was maintained for up to three months in formulations with varying TG content and up to four months in those with varying UC content. Thereafter, a progressive increase in nanoparticle size was observed, which suggests enhanced aggregate formation and reduced of LDE stability between 3 and 6 months of storage. This loss of stability did not appear to be directly related to changes in UC or TG composition. Notably, USAXS and DLS measurements yielded comparable results, which reinforces the reliability of the data. In addition, the zeta potential remained close to zero for all seven nanoparticle compositions throughout the six months, indicating that all LDE formulations had electrostatic neutral potential and remain so when they progressively aggregate with time. Complementary analyses also showed that LDE particles are, on average, spherical in shape. Overall, these findings provide relevant insights for the rational design of lipid mixtures in the preparation of nanoemulsions for drug delivery applications. Show less

Early diagnosis of familial hypercholesterolemia (FH) is crucial to improve long-term outcomes. FH diagnosis relies on elevated low-density lipoprotein cholesterol (LDL-C) levels, familial clinical characteristics, and identification of pathogenic variants in FH-related genes. Secondary factors, such as overweight and obesity, are known to influence lipid profiles in the general population. More recently, polygenic risk scores based on single-nucleotide polymorphisms (SNPs) have been proposed as additional determinants of LDL-C levels. We enrolled 214 pediatric subjects with LDL-C levels ≥95th percentile (after 6 months of dietary intervention) and with at least one parent with LDL-C levels ≥ 95th percentile. All participants underwent biochemical and auxological assessment and genetic testing for FH. In a subgroup of 60 subjects, LDL-C polygenic scores based on 6- and 12-SNPs were calculated. Pathogenic variants confirming heterozygous FH were identified in 190 subjects (variant-positive, V+); 17 were variant-negative (V-), yielding a mutation detection rate of 91.8%. An additional seven patients carrying variants of uncertain significance were excluded from the primary analysis. LDL-C was modestly higher in V+ than V- subjects using both Friedewald (212 vs. 188 mg/dL; In children selected by LDL-C ≥ 95th percentile, together with autosomal dominant familial hypercholesterolemia, genetic confirmation of FH is achieved in the vast majority of cases. Variant type (null vs. defective), BMI, and polygenic background contribute to phenotypic heterogeneity, supporting the need to address other factors alongside genetic diagnosis. Further validation is needed before polygenic scores can be implemented in routine clinical practice. Show less

Research suggests that lipid levels may be associated with suicide risk. However, the specific relationship between Apolipoprotein B and suicidal ideation remains unclear. The aim of this study was to investigate the association between ApoB levels and suicidal ideation and to further explore the causal relationship using Mendelian randomization. A cross-sectional study of 6520 U.S. adults was conducted using the 2011-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Multiple logistic regression, smoothed curve fitting, stratified analyses, and interaction tests were used to reveal the relationship between ApoB levels and suicidal ideation. MR analyses were conducted using inverse variance weighting (IVW), GSMR, Maximum likelihood method, and cML-MA-BIC MR method. Sensitivity analyses included MR-Egger intercept test, MR-PRESSO global test, and leave-one-out (LOO) analysis. Multivariate logistic regression analysis showed that serum ApoB levels were positively associated with suicidal ideation, and the association remained significant even after multiple covariates (P = 0.0463). Subgroup analyses showed that the risk of suicidal ideation was significantly increased in the highest tertile (T3) of the population compared to the lowest tertile (T1) of ApoB levels (OR = 1.48, 95% CI: 1.04-2.12, P = 0.0312). In addition, the association between ApoB and suicidal ideation was more significant in the smoking subgroup (P interaction = 0.034). However, MR analysis failed to confirm a significant causal effect of ApoB levels on suicidal ideation (P > 0.05), and these results were robust to sensitivity analyses. The present study found a significant positive association between serum ApoB levels and suicidal ideation, especially among smokers. MR analysis failed to provide causal evidence of ApoB on suicidal ideation. More research is needed to clarify the potential role of ApoB in the development of suicidal ideation. Show less

Ischemic stroke is a heterogeneous disease influenced by inflammation, coagulation dysfunction, and metabolic disturbances. However, integrated analysis incorporating these biological domains for patient stratification remain limited. A retrospective study of 132 ischemic stroke patients was conducted. Clinical, coagulation, inflammatory, and metabolic parameters were collected. Principal component analysis (PCA) was applied for dimensionality reduction and visualization. PCA revealed underlying heterogeneity among patients. Validated Data driven clustering identified biologically distinct ischemic stroke subtypes based on inflammation, coagulation, and metabolic profiles. This stratification highlights the heterogeneity of ischemic stroke and may inform future personalized approaches to risk assessment and management. Show less

Enlicitide decanoate, an oral proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, was shown to reduce low-density lipoprotein (LDL) cholesterol levels in a phase 2 trial; longer-term data are needed. In this multinational, double-blind, randomized, placebo-controlled trial, we enrolled adults with a history of a major atherosclerotic cardiovascular disease event with an LDL cholesterol level of 55 mg per deciliter or higher and those who were at risk for a first atherosclerotic cardiovascular disease event with an LDL cholesterol level of 70 mg per deciliter or higher. Participants were assigned in a 2:1 ratio to receive enlicitide at a dose of 20 mg or placebo daily for 52 weeks. The primary end point was the mean percent change in LDL cholesterol level from baseline to week 24. Key secondary end points were the mean percent change in LDL cholesterol level at week 52 and the mean percent change in levels of non-high-density lipoprotein (non-HDL) cholesterol and apolipoprotein B and the percent change in lipoprotein(a) level at week 24. Of the 2909 participants in the intention-to-treat population, 1935 received enlicitide and 969 received placebo (5 did not receive enlicitide or placebo). The mean age of the participants was 63 years, and 39.3% were women. The mean (±SD) LDL cholesterol level at baseline was 96.1±38.9 mg per deciliter. The mean percent change in LDL cholesterol levels at week 24 was -57.1% (95% confidence interval [CI], -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001). The mean percent change in LDL cholesterol level at week 52, the mean percent changes in non-HDL cholesterol and apolipoprotein B levels at week 24, and the percent change in lipoprotein(a) levels at week 24 were significantly greater with enlicitide than with placebo (P<0.001 for all comparisons). The incidence of adverse events did not appear to differ between the groups. Among participants who had a history of or were at risk for a first atherosclerotic cardiovascular disease event, treatment with the oral PCSK9 inhibitor enlicitide resulted in significantly lower LDL cholesterol levels than placebo at 24 weeks. (Funded by MSD [Rahway, NJ]; CORALreef Lipids ClinicalTrials.gov number, NCT05952856.). Show less

Residual cardiovascular risk persists in statin-treated patients with coronary artery disease (CAD), even when low-density lipoprotein cholesterol (LDL-C) targets are met. Excess apolipoprotein B (apoB), defined as measured apoB minus LDL-C-predicted apoB, may capture atherogenic particle burden beyond LDL-C, but its prognostic value for long-term mortality in secondary prevention remains uncertain. We conducted a pooled analysis of two nationwide Chinese cohorts (CIN-II and RED-CARPET) comprising 68,616 statin-treated CAD patients. Excess apoB was calculated using an internal reference population (triglycerides ≤ 1.0 mmol/L). Associations with all-cause and cardiovascular mortality were assessed using multivariable Cox models, with adjustment for clinical covariates including nutritional status. External validation was performed in 13,702 participants from the UK Biobank. Over a median follow-up of 5.2 years, 10,835 deaths occurred (5,090 cardiovascular). Each 1-standard deviation (15.4 mg/dL) increase in excess apoB was associated with a 12% higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.12, 95% CI 1.06-1.18) and a 24% higher risk of cardiovascular mortality (aHR 1.24, 95% CI 1.15-1.34). Patients in the highest excess apoB quartile (≥ 11.5 mg/dL) had significantly worse survival. Notably, these associations persisted consistently across all achieved LDL-C strata (< 2.0 to > 4.0 mmol/L). These findings were robustly confirmed in the external validation cohort. Excess apoB is an independent predictor of long-term mortality in statin-treated CAD patients, even among those with well-controlled LDL-C. Its incorporation into risk assessment could improve prognostic stratification and guide personalized management in secondary prevention. CIN-II: ClinicalTrials.gov, NCT05050877 (Retrospectively registered, 21 September 2021); RED-CARPET: Chinese Clinical Trial Registry, ChiCTR2000039901 (Prospectively registered, 14 November 2020). The UK Biobank study is covered by generic ethical approval from the NHS National Research Ethics Service (Ref: 99231). Show less

Oxidative modification of apolipoprotein B-100 (apoB) containing particles and subsequent immune responses contribute to the pathogenesis of atherosclerosis. Circulating IgG and IgM apoB-containing immune complexes (apoB-IC) and autoantibodies to a malondialdehyde mimotope (anti-MDA-mimotope) serve as biomarkers of oxidative stress and immune activation in atherosclerotic cardiovascular disease. Elevated lipoprotein(a) [Lp(a)] is associated with increased oxidative burden and immune activation. To investigate the effect of lipid-lowering medications on IgG and IgM apoB-IC and IgG and IgM autoantibodies to an MDA-mimotope in individuals with elevated lipoprotein(a) [Lp(a)] concentrations. In this prospective study, patients (n = 70) with Lp(a) levels ≥ 75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). IgG and IgM apoB-IC and IgG and IgM anti-MDA-mimotope were measured at baseline and 3 months after treatment initiation. Patients had a mean age of 51 ± 15 years and 40% were male. Significant reductions in IgG apoB-IC levels were observed following treatment with high-intensity statins, add-on ezetimibe and add-on PCSK9i (by 18.3%, 17.5% and 25.5%, respectively, all p < 0.05). No significant changes in IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels were observed in any treatment group. In individuals with Lp(a) levels ≥ 75 nmol/L, high-intensity statins, add-on ezetimibe and add-on PCSK9i reduced IgG apoB-IC but did not affect IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels. The clinical significance of these findings warrants further investigation. Show less

Lipoprotein(a)-targeted therapies are emerging approaches for lowering lipoprotein(a) [lp(a)]. We conducted a systematic review and network meta-analysis to evaluate the efficacy and safety of lipoprotein(a)-targeted therapies in patients. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to May 6, 2025, for randomized controlled trials (RCTs) with intervention duration of at least 12 weeks. The primary outcomes were percentage and absolute changes in Lp(a). Secondary outcomes included changes in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), and safety outcomes including adverse events (AEs), serious adverse events (SAEs), and injection-site reactions. A frequentist framework network meta- analysis was performed. Nine studies involving 1,432 participants were included. All six Lp(a)-targeted therapies significantly reduced Lp(a) levels. Compared with placebo, Olpasiran was the most effective therapy for both percentage [mean difference: -92.06, 95% (-109.80; -74.32), Lp(a)-targeted therapies achieved substantial reductions in Lp(a). Olpasiran was the most effective agent in lowering Lp(a) levels. These therapies also improved LDL-C and apoB. The majority of Lp(a)-targeted therapies demonstrate generally favorable safety profiles; However, injection-site reactions, particularly with Zerlasiran, warrant careful consideration. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251069288, PROSPERO CRD420251069288. Show less

RNA-based therapies have emerged as a transformative approach in the management of hypercholesterolemia and coronary artery disease by directly targeting molecular pathways involved in lipid regulation. These treatments focus on silencing key genes such as PCSK9, ANGPTL3, ApoB, and Lp(a), achieving substantial reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and other atherogenic lipoproteins. Small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) provide highly specific post-transcriptional gene suppression, while advances in chemical stabilization and GalNAc conjugation have enhanced hepatocyte delivery and prolonged therapeutic action. Approved agents such as inclisiran demonstrate sustained LDL-C reductions of approximately 50% with only two to three injections annually, improving adherence and offering an alternative for patients intolerant to statins or unable to reach lipid targets with conventional therapy. Pelacarsen and other emerging antisense therapies show promise for reducing lipoprotein(a), an independent cardiovascular risk factor, while siRNAs targeting ANGPTL3 offer prolonged lipid-lowering effects beyond those achieved with monoclonal antibodies. Despite these advantages, challenges remain. Hepatic safety concerns have halted the development of some agents, such as vupanorsen, and long-term cardiovascular outcome data for several therapies, including inclisiran, are still in development. Cost and accessibility also limit broad adoption, emphasizing the need for cost-effective strategies and long-term surveillance. Nevertheless, current evidence supports the integration of RNA-based therapies into modern lipid-lowering algorithms, particularly for high-risk patients, while ongoing research continues to refine delivery systems, enhance safety, and expand therapeutic indications. Show less

We previously reported that triazine thiols reduce apolipoprotein B (ApoB) secretion from human iPSC-derived hepatocytes (HLCs) and from humanized mice. To determine whether these compounds affected hepatocyte mRNA levels, we performed bulk RNA sequencing of HLCs treated with the triazine thiol DL-1 or with vehicle (DMSO) for 24 hours. Analyses revealed that in triazine thiol-treated cells, 145 mRNAs were reduced and 37 increased by ≥ 2-fold.  Several mRNAs encoding cysteine-rich metallothionines were upregulated, implying that HLCs respond to treatment by mounting a protective response through metal buffering. Show less

In recent years, human exposure to p-phenylenediamine-derived quinone (PPD-Qs) has attracted great attention due to their potential toxic effects on humans. While, their potential health risks to the lipid metabolism in humans remain inadequately elucidated. This cross-sectional study analyzed blood samples for six PPD-Qs, lipid profiles, and mitochondrial DNA copy number (mtDNAcn), and investigated the association between PPD-Q exposure and lipid levels in a population-based cohort comprising 255 healthy Chinese adults. Results showed that PPD-Qs in human serum was dominated by 6PPD-Q (mean 1.8 ng/mL), followed by 77PD-Q (0.73 ng/mL) and DTPD-Q (0.60 ng/mL). Multivariate analyses demonstrated significantly positive correlations between exposure to specific PPD-Qs (i.e., 6PPD-Q, CPPD-Q, DPPD-Q, and DTPD-Q) and elevated serum concentrations of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Weighted quantile sum regression showed that mixed PPD-Q exposure was positively correlated with TG levels (β = 0.050, 95% CI: 0.009 -0.16), with 6PPD-Q showing the highest weight for TC (weight 0.27), TG (0.31), low-density lipoprotein (0.28), apolipoprotein A1 (ApoA1; 0.52), and apolipoprotein B (ApoB; 0.33). Bayesian kernel machine regression analysis confirmed dose-dependently positive relationships between combined PPD-Q exposure and TC, TG, LDL-C, ApoA1, and ApoB. Mechanistically, mtDNAcn mediated 34 (95% CI: 9.3 -138%)-70% (95% CI: 12 -266%) of the total serum TG-elevating effects induced by PPD-Q exposure, revealing a novel pathway through which these PPD-Qs disrupt lipid homeostasis. Findings of this study address critical knowledge gaps regarding the toxicological impacts of these emerging environmental contaminants on human metabolic health. Show less

Apolipoprotein B (apoB) is a recognized risk factor for acute coronary syndrome (ACS); however, its prognostic value in secondary prevention and superiority over other lipid biomarkers, especially in younger populations, remains uncertain. To investigate whether elevated baseline apoB predicts recurrent cardiovascular events in patients who experienced an ACS at ≤40 years of age and compare its incremental predictive value with that of other lipid biomarkers. We recruited 405 consecutive patients who survived an ACS at ≤40 years of age. Clinical endpoints included major adverse cardiovascular events (MACE): cardiac death, readmission for ACS or ventricular arrhythmias, ischemic stroke, and coronary revascularization due to clinical deterioration. The association between baseline lipid biomarkers and recurrent MACE risk was assessed using multivariable Cox regression. Model performance was evaluated based on discrimination and reclassification. Of 378 young ACS survivors (33.7 ± 4.3 years) with follow-up data, 139 (36.8%) experienced a MACE over a median 8-year (5.2-12.5 years) follow-up. Elevated baseline apoB was independently associated with a higher risk of recurrent MACE (hazard ratio per 10 mg/dL: 1.082, P= .007). This association remained significant even after additionally accounting for low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). Conversely, apoB adjustment attenuated the LDL-C and non-HDL-C associations. Compared with LDL-C and non-HDL-C, apoB was associated with greater risk of recurrent MACE, and upon addition to conventional cardiovascular risk factors, yielded the greatest improvement in discrimination and reclassification. Baseline apoB may act as a driver for long-term recurrence of MACE in very young ACS survivors, highlighting its potential clinical utility to improve risk stratification beyond traditional lipid measurements. Show less

Many randomised controlled trials (RCTs) have revealed the benefits of walnut on apolipoproteins and blood pressure, but the results are inconclusive. This meta-analysis of RCTs aimed to assess the effects of walnut on Apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1) and blood pressure. A systematic review of PubMed, Scopus, Web of Science, Cochrane and Embase databases was conducted, and the search time frame was from the establishment of the database up to January of 2025. A random effects model was applied to estimate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Twenty-five RCTs comprising 26 intervention arms with 2155 patients were included. Walnut significantly decreased ApoB (WMD = -0.06; 95% CI: -0.10, -0.01, p = 0.002), but did not affect ApoA1 (WMD = -0.50; 95% CI: -1.34, 0.33, p = 0.249), systolic blood pressure (SBP) (WMD = -1.20; 95% CI: -4.02, 1.61, p = 0.401) and diastolic blood pressure (DBP) (WMD = -0.44; 95% CI: -2.55, 1.67, p = 0.682). Walnut intake was associated with reduced ApoB levels, with no significant effects observed on ApoA1, SBP, or DBP. Future research involving large-scale, international RCTs is essential to validate its therapeutic potential further. Show less

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Increasing evidence implicates systemic lipid perturbation in ALS pathogenesis. However, the extent and nature of apolipoprotein changes underlying lipid perturbations in ALS remain largely unknown. To address this, we performed a comprehensive analysis of major apolipoproteins involved in lipid metabolism and examined their association with lipoprotein membrane lipids in sporadic ALS (n = 32) and age-matched healthy controls (n = 32), using ELISA and liquid chromatography-mass spectrometry. Compared with controls, serum levels of apoB, apoCI, apoCII, apoCIII and apoE were significantly elevated in ALS, whereas apoAI and apoAII were unchanged. Distributional analyses demonstrated a relative decrease in apoAI and an increase in apoB in ALS, resulting in an elevated apoB/apoAI ratio, a marker of atherogenic risk, alongside a reduced apoAI/apoE ratio. Correlation analyses revealed strengthened interrelationships among apolipoproteins in ALS, suggesting altered regulatory coordination. At the lipid level, phosphatidylcholine (PC) was increased, whereas sphingomyelin (SM) was reduced in ALS serum. Notably, the strong associations of apoB to both PC and SM observed in controls were absent in ALS. Biomarker analyses identified apoE as the strongest discriminator between ALS and control groups. Collectively, these findings demonstrate a coordinated disruption of apolipoproteins and lipoprotein-associated lipids in ALS serum, with likely functional consequences for lipoprotein metabolism. This study provides new insights into lipid dysregulation in ALS pathobiology and supports the emerging view that ALS encompasses not only neurodegenerative processes but also systemic metabolic reprogramming. Show less

In order to address the challenge of early detection of ascending aortic dilation (AAD) in patients with bicuspid aortic valve (BAV), a machine learning prediction model integrating ultrasound hemodynamics and serum markers was developed to break through the limitations of traditional anatomical indicators. A total of 51 patients with BAV were prospectively enrolled and divided into ascending aortic dilation group (BAV-D, AAoV, AAoMPG and HDL-C in the BAV-D group were significantly higher than those in the BAV-ND group (all The machine learning model constructed by integrating hemodynamics (AAoV) and metabolic markers (HDL-C and ApoB) for the first time can accurately quantify the risk of AAD in BAV patients, and its performance is significantly better than that of a single anatomical parameter, providing a visual decision-making tool for early intervention. Show less

Clutch length is a key determinant of reproductive efficiency in geese and strongly positively correlates with egg production. We recorded daily egg production in 280 individually housed Zi geese, calculated clutch-related indices, and selected 12 geese to form long-clutch (LC) and short-clutch (SC) groups for ovarian transcriptomic, proteomic, and metabolomic analyses. The results showed that egg number, large clutch length, large clutch number, average clutch length, and average clutch number were significantly higher in LC than in SC groups (P < 0.0001). Transcriptomic analysis identified 885 differentially expressed genes enriched in oocyte development and ovarian steroidogenesis, with APOB, PLA2G4C, MMP2, MMP9, and NOBOX as key genes; proteomic analysis identified 437 differentially abundant proteins enriched in arachidonic acid metabolism and mitophagy, with CXCL12, RARB, and MAD2L1 as key proteins; and metabolomic analysis identified 35 differentially abundant metabolites enriched in glycolysis/gluconeogenesis, with lactic acid, guanidinoacetic acid, and 3-hydroxybutyrylcarnitine as key metabolites. Integration of multi-omics datasets highlighted a lactate-associated cross-omics signature supported by YWHAZ at the protein level and by the lactate transporter SLC16A3. Collectively, these findings deepen our understanding of the molecular basis underlying clutch-length variation in goose ovaries and highlight candidate genes, proteins, and metabolites for future functional validation. Show less

T2D mellitus (T2DM) is increasingly prevalent in South Asia, often affecting individuals with normal BMI, a phenotype described as metabolically obese but normal weight (MONW). While randomized trials demonstrate that low-carbohydrate diets can induce remission, long-term, real-world evidence in non-obese, predominantly vegetarian South Asian populations remains scarce. To evaluate the long-term efficacy and safety of a culturally adapted low-carbohydrate diet in an N-of-1 longitudinal study with systematic, multi-domain follow-up. A 49-year-old male with new-onset T2D (HbA1c 7.2%) began a phased initiation (~100 g/day carbohydrate), nutritional ketosis (<30 g/day carbohydrate), and long-term stabilization (~100 g/day). Assessments included continuous glucose monitoring (CGM) periodically, standardized mixed-meal challenges, advanced lipid and apolipoprotein panels including ApoB and lipoprotein(a) [Lp(a)], hs-CRP, liver and renal function, and serial cardiovascular, skeletal, and ophthalmic imaging over 10-years. The study was monitored through regular physician assessments and follow-up. HbA1c remained between 4.7 and 5.3% without medication for a decade. CGM showed >90% time-in-range with reduced variability (CV decreased from approximately 18-12%), Lp(a) decreased (43.4 → 25.3 mg/dL), and hs-CRP remained <1 mg/L. Coronary artery calcium (CAC) remained 0 across three scans, with CT angiography confirming CAD-RADS 0. CIMT showed no stenosis. Bone mineral density and ophthalmic imaging showed no deterioration. This report offers a detailed N-of-1 longitudinal characterization of decade-long, medication-free remission of T2D in a metabolically obese normal weight South Asian male. Observations at approximately 100 g per day carbohydrate intake suggest that moderate carbohydrate restriction may represent a physiologically plausible and culturally compatible approach for long-term metabolic management in similar phenotypes. While broader applicability requires validation in larger cohorts, these findings provide a rationale for further evaluation of moderate carbohydrate restriction as a feasible dietary strategy in South Asian and comparable settings. Show less

The intestine acts as the primary site for absorption of dietary lipids. These lipids are packaged and transported via lipoprotein complexes, whose altered levels correlate with metabolic disease.  The Show less

Copper overload has been implicated in impaired A total of 117 patients with T2DM (mean age 55.15 ± 10.70 years; 62.4% male) were included. Whole blood copper concentration was measured using inductively coupled plasma mass spectrometry. Associations between blood copper and glycemic indicators, including glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG), were evaluated using multivariable linear regression models. Stratified and interaction analyses were performed according to apoB and other lipid-related parameters. After adjustment for potential confounders, a significant interaction between blood copper and apoB was observed in relation to HbA1c (P for interaction< 0.001). Stratified analyses showed that higher blood copper concentration was significantly associated with higher HbA1c levels among patients with lower apoB levels below the study median, whereas no significant association was observed among those with higher apoB levels. Exploratory analyses further indicated that apoB also influenced the association between blood copper and FPG (P for interaction< 0.05), showing a consistent pattern. In patients with T2DM, a significant association between blood copper concentration and glycemic control was observed among individuals with lower apoB levels, whereas no such association was found among those with higher apoB levels. These findings suggest that apoB status may influence the relationship between blood copper and glycemic control and merit further investigation in longitudinal studies. Show less

Dyslipidemia is a universal finding in nephrotic syndrome with relapse, but there are limited data on its prevalence in disease remission. Primary objectives of the study were to identify dyslipidemia and analyze the profile of serum apolipoproteins and lipoprotein(a) in children with nephrotic syndrome in disease remission. This cross-sectional study included children (2-18 years) with nephrotic syndrome. A detailed history was elicited, and an examination was performed; blood investigations included glycosylated hemoglobin, serum albumin, kidney function tests (KFT), fasting lipid profile, serum apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), and lipoprotein(a), and a spot urine for urine protein-to-creatinine ratio. The median age (IQR) of 92 enrolled children (male 65; female 27) was 8 (6-11) years. Forty-seven had steroid-sensitive nephrotic syndrome (SSNS), 29 had steroid-resistant nephrotic syndrome (SRNS) in disease remission, and 16 were in relapse and included for comparison. Dyslipidemia was seen in 39.5%, with a prevalence of 32% in SSNS, 51.7% in SRNS during remission, and 100% in children in relapse, using conventional markers. ApoB/ApoA-1 ratio ≥0.6 was seen in 14.2% and 29.6% of children with SSNS and SRNS, respectively, while a ratio ≥0.8 was seen in only 5.2% of those in remission. The median values of the ApoB/ApoA-1 ratio in remission and relapse were 0.5 (0.4-0.6) and 0.85 (0.62-1.33), respectively. ApoB, ApoA-1, and ApoB/ApoA-1 showed sensitivities of 63.3%, 40%, and 13.3%, and specificities of 82.6%, 80.4%, and 100%, respectively, for the diagnosis of dyslipidemia, and receiver operator characteristic analysis showed area under the curve of 0.704, 056, and 0.65, respectively. Identification of dyslipidemia using conventional parameters may lead to overdiagnosis in nephrotic syndrome during disease remission; the ApoB/ApoA-1 ratio appears to be a better marker. Show less