The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with statins in patients with hypercholesterolemia: a network meta-analysis.

Background: In recent years, the position of PCSK9 inhibitors as adjuvant therapy to statins in guidelines has further improved. However, there remained a dearth of direct comparative studies among different PCSK9 inhibitors. Therefore, this study aimed to conduct a network meta-analysis to evaluate the efficacy and safety of different PCSK9 inhibitors combined with statins. Methods: A comprehensive literature search was conducted from the study's inception to 12 November 2023, encompassing multiple online databases including PubMed, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov to obtain relevant randomized controlled trials. Frequentist network meta-analysis was employed to compare the efficacy and safety of different PCSK9 inhibitors. The efficacy endpoints were low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)). The safety endpoints were any adverse events (AE), severe adverse events (SAE), AE leading to treatment discontinuation, and injection-site reaction. Results: Compared with placebo and ezetimibe, all PCSK9 inhibitors demonstrated significant reductions in LDL-C levels. Notably, evolocumab exhibited the most pronounced effect with a treatment difference of -63.67% (-68.47% to -58.87%) compared with placebo. Regarding dosage selection for evolocumab, the regimen of 140 mg Q2W (-69.13%, -74.55% to -63.72%) was superior to 420 mg QM (-61.51%, -65.97% to -57.05%). Based on rankings and P-scores analysis, tafolecimab 150 mg Q2W demonstrated superior efficacy in reducing ApoB levels (-61.70%, -84.38% to -39.02%) and Lp(a) levels (-43%, 30%, -68%, 81% to -17%, 79%). Furthermore, the safety profile of PCSK9 inhibitors was favorable with no increase in the incidence of AE, SAE, or AE leading to treatment discontinuation; however, alirocumab, inclisiran, and tafolecimab may potentially entail a potential risk associated with injection-site reactions. Conclusion: Compared with placebo and ezetimibe, PCSK9 inhibitors can significantly reduce LDL-C, ApoB, and Lp(a) when combined with statins to treat hypercholesterolemia. Furthermore, PCSK9 inhibitors and ezetimibe exhibit similar safety profiles. Systematic Review Registration: [PROSPERO], identifier [CRD42023490506].

The relationship between early-onset coronary artery disease and familial hypercholesterolemia: a cohort study based on the Hakka population in Meizhou, China.

BACKGROUND: The low diagnosis and treatment rates of familial hypercholesterolemia (FH) have become a global issue. This study aims to explore the correlation between early-onset coronary artery disease (CAD) and FH in the Hakka population in Meizhou, Guangdong. METHODS: Clinical data of Hakka patients with early-onset CAD, admitted to the Meizhou People's Hospital from January 2023 to January 2024 were retrospectively analyzed. The patients were categorized into an FH group and a non-FH group. Biochemical indicators, lipid levels, echocardiographic parameters, clinical phenotypes, and genetic typing of early-onset CAD patients in the Hakka population were analyzed for their correlation with FH. RESULTS: A total of 167 Hakka patients with early-onset CAD were included, among whom 22 patients had FH. The FH group showed lower triglyceride (TG) level [1.785 (1.40, 2.10) vs. 2.090 (1.80, 2.30), P = 0.002] and higher levels of total cholesterol (TC) [6.635 (5.60, 7.10) vs. 4.830 (4.00, 5.40), P<0.001], low-density lipoprotein cholesterol (LDL-C) [4.440 (3.90, 5.20) vs. 2.820 (2.40, 3.30), P<0.001], and apolipoprotein B (Apo B) [1.600 (1.30, 1.80) vs. 0.910 (0.70, 1.10), P<0.001]. FH was correlated with TG, TC, LDL-C and Apo B levels (r1 = -0.235; r2 = 0.441; r3 = 0.483; r4 = 0.538). TG is a risk factor while TC, LDL-C and Apo B are protective factors for FH. CONCLUSION: The incidence of FH is relatively high among early-onset CAD patients in the Hakka population in Meizhou. TG, TC, LDL-C, and Apo B levels are valuable in aiding clinical differential diagnosis of CAD patients with FH.

A Comparative Analysis of Low-Density Lipoprotein Cholesterol (LDL-C)-Lowering Activities of Bempedoic Acid, Inclisiran, and PCSK9 Inhibitors: A Systematic Review.

Newer drugs, such as bempedoic acid, inclisiran, alirocumab, and evolocumab have recently been introduced for dyslipidemia. This systematic review aims to perform a comparative analysis of these drugs' low-density lipoprotein cholesterol (LDL-C)-lowering activities. The PubMed database was utilized to search for randomized controlled trials. Articles were screened and selected based on specific inclusion and exclusion criteria. The primary outcome of this review is to compare the percentage reduction of LDL-C and apolipoprotein-B, along with the number of reported serious adverse events (SAEs) in trials specific to each drug. A total of 14 studies were included, four for bempedoic acid and alirocumab and three for evolocumab and inclisiran. The maximum percentage reduction in LDL-C and apolipoprotein-B from baseline to 12 weeks was observed with alirocumab, administered at 150 mg subcutaneously twice weekly for 12 weeks, achieving reductions of 72.4% and 57.9%, respectively. Lesser reductions were observed with bempedoic acid, administered at 180 mg once daily orally for 12 weeks. The highest number of SAEs were reported with bempedoic acid (216, 10%) and inclisiran (181, 11%; 175, 11%). This systematic review showed that alirocumab achieved the greatest reductions in LDL-C and apolipoprotein-B and a better safety profile. Newer LDL-C-lowering drugs show promise in improving lipid profiles, patient compliance, and safety. However, these findings are not conclusive, as other factors also influence treatment choice.

Apolipoprotein B-48 and late graft failure in kidney transplant recipients.

Introduction: Transplant vasculopathy resembles atherosclerotic plaque formation and is a major contributor to late graft failure in kidney transplant recipients (KTR). Remnant lipoproteins and associated triglycerides are causal risk factors for atherosclerotic plaques and have been implicated in late kidney graft failure. However, whether remnants derived from liver (containing apolipoprotein [apo] B100) or intestine (containing apoB48) are clinically more important is unclear. The current study investigated the association between baseline fasting apoB48 levels and late kidney graft failure. Methods: 481 KTR with a functioning graft for at least 1 year were included in this retrospective, observational longitudinal single center cohort study. The primary endpoint was death-censored late graft failure, defined as need for initiation of dialysis or re-transplantation. ApoB48 was measured by enzyme-linked immunosorbent assay. Results: During a median follow-up of 9.5 years, 61 KTR developed graft failure (12.7%). At baseline, KTR with higher apoB48 levels had lower eGFR (P < .001), lower high-density lipoprotein (HDL) cholesterol (P < .001), increased triglycerides (P < .001) and used cyclosporine more frequently (P = .003). Cox regression showed that higher baseline apoB48 was associated with higher risk of late graft failure [hazard ratio (95% confidence interval), 1.59 (1.22, 2.07), P < .001], independent of stepwise adjustment for potential confounders, including age and sex, immunosuppression type and proteinuria, triglycerides, and waist circumference (fully adjusted HR, 1.78 (1.29, 2.47), P < .001]. Conclusion: ApoB48 is strongly associated with late graft failure, independent of potential confounders. Since apoB48-containing lipoproteins originate from the intestine, this study provides a rationale for considering pharmacological interventions targeting lipid absorption to improve graft outcome.

Naringenin modulates oxidative stress and lipid metabolism: Insights from network pharmacology, mendelian randomization, and molecular docking.

Background: Previous studies have demonstrated that naringenin possesses lipid-lowering effects; however, the underlying mechanisms, particularly its specific molecular targets, remain uncertain. Methods: Using bioinformatics, three traditional Chinese medicine databases and one human disease database were integrated to establish two naringenin-target-hyperlipidemia modules: naringenin-oxidative stress (OS) and naringenin-lipid metabolism (LM). Data on 1,850 proteins from 1,871 genetic instruments were sourced from seven previous studies. Using Mendelian randomization based on data from the Integrative Epidemiology Unit genome-wide association study (case, n = 5,153; control, n = 344,069), we identified potential drug targets that were subsequently validated in the UK Biobank (396,565 individuals) and FinnGen (412,181 individuals) cohorts. Using molecular docking and molecular dynamics simulation to verify the binding ability of naringenin and causal protein. Results: In plasma, every standard deviation increase in apolipoprotein B (APOB) was associated with an increased risk of hyperlipidemia (odds ratio [OR] = 9.37, 95% confidence interval [CI], 5.12-17.12; P = 3.58e-13; posterior probability of hypothesis 4 [PPH4] = 0.997), and the same was observed for proprotein convertase subtilisin/kexin type 9 (OR = 1.81, 95% CI, 1.51-2.16; P = 6.87e-11; PPH4 = 1) and neurocan (OR = 2.34, 95% CI, 1.82-3.01; P = 4.09e-11; PPH4 = 0.932). The intersection of two modules and Mendelian randomization result identified APOB as a key regulatory target of naringenin in the treatment of hyperlipidemia. The binding energy between naringenin and APOB was determined to be -7.7 kcal/mol. Additionally, protein-protein interactions and protein-disease networks were analyzed to uncover potential connections between proteins and hyperlipidemia. Conclusion: This Mendelian randomization-based combined analysis offers a robust framework for elucidating the pharmacological effects of naringenin and identifying candidate proteins for further investigation in the context of hyperlipidemia treatment.

Low-Density Lipoprotein Receptor Apolipoprotein B Gene Polymorphism in Kurdish Patients With Severe Hypercholesterolemia.

Background Polymorphisms in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB-100) genes have been linked to severe hypercholesterolemia in several populations. This study investigated the frequency of LDLR-Ava II and APOB-Xba I polymorphisms among Kurdish patients with severe hypercholesterolemia. Methodology We investigated LDLR-Ava II and APOB-Xba I gene polymorphisms in Kurdish patients attending the Duhok Specialized Laboratory Center in Duhok, Kurdistan Region, Iraq. We included a total of 80 subjects in this study, of which 40 (20 males and 20 females) had severe hypercholesterolemia, and 40 apparently healthy volunteers (21 males and 19 females) had normocholesterolemia, served as a control group. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to determine the polymorphisms of the LDLR-Ava II and APOB-Xba I genes. Results In those with severe hypercholesterolemia, the observed allele frequencies were AA LDLR-Ava II polymorphism (eight, 20%) followed by TT APOB-Xba I polymorphisms (six, 15%), whereas these frequencies were five (12.5%) and one (2.5%) in those with normocholesterolemia, respectively. The AA genotype group had considerably higher cholesterol and LDL-C levels compared with the GG genotype group. A similar pattern was observed when comparing the TT and CC genotype groups. Conclusions Our results showed a high frequency of AA LDLR-Ava II polymorphism in conjunction with TT APOB-Xba I polymorphism which may be strongly associated with hypercholesterolemia in the Kurdish population.

Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis.

This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.

J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome.

INTRODUCTION AND OBJECTIVES: The association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. METHODS: We enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73g/L, after which the risk increased (nonlinear P <.05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤0.57g/L) and high (Q5, >0.93g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P <.05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). CONCLUSIONS: Our analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73g/L).

Lipoprotein(a) and risk-weighted apolipoprotein B: a novel metric for atherogenic risk.

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

Genetic association analyses highlight apolipoprotein B as a determinant of chronic kidney disease in patients with type 2 diabetes.

BACKGROUND: Blood lipid levels were associated with chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), but the genetic basis and causal nature remains unclear. OBJECTIVE: This study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D. METHODS: Our prospective analysis involved 8,607 White participants with T2D but no CKD at baseline from the UK Biobank. Five common lipid traits were included as exposures. Weighted genetic risk scores (GRSs) for these lipid traits were developed. The causal associations between lipid traits, as well as lipid fractions, and CKD were explored using linear or nonlinear Mendelian randomization (MR). The 10-year predicted probabilities of CKD were evaluated via integrating MR and Cox models. RESUTLS: Higher GRS of apolipoprotein B (ApoB) was associated with an increased CKD risk (HR[95 % CI]:1.07[1.02,1.13] per SD;P = 0.008) after adjusting for potential confounders. Linear MR indicated a positive association between genetically predicted ApoB levels and CKD (HR[95 % CI]:1.53[1.12,2.09];P = 0.008), but no evidence of associations was found between other lipid traits and CKD in T2D. Regarding 12 ApoB-contained lipid fractions, a significant causal association was found between medium very-low-density lipoprotein particles and CKD (HR[95 % CI]:1.16[1.02,1.32];P = 0.020). Nonlinear MR did not support nonlinearity in these causal associations. The 10-year probability curve showed that ApoB levels was positively associated with the risk of CKD in patients with T2D. CONCLUSION: Lower ApoB levels were causally associated with a reduced risk of CKD in patients with T2D, positioning ApoB as a potential therapeutic target for CKD prevention in this population.

Fibrinogen and plasma clot properties are associated with apolipoprotein B and apolipoprotein B-containing lipoproteins in Africans.

BACKGROUND: Case-control, intervention and laboratory studies have demonstrated a link between apolipoprotein B-containing lipoproteins and clot structure and thrombosis. There is, however, limited evidence on population level. OBJECTIVES: We determined the cross-sectional relationship between lipoprotein(a) (Lp(a)), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) with fibrinogen and plasma clot properties in 1 462 Black South Africans, a population with higher fibrinogen and Lp(a) levels compared with individuals of European descent. METHODS: Data were obtained from participants in the South African arm of the Prospective Urban and Rural Epidemiology study. Clot properties analysed included lag time, slope, maximum absorbance, and clot lysis time (turbidity). Lp(a) was measured in nM using particle-enhanced immunoturbidimetry. General linear models (GLM) were used to determine the associations between ApoB and ApoB-containing lipoproteins with fibrinogen and plasma clot properties. Stepwise regression was used to determine contributors to clot properties and Lp(a) variance. RESULTS: GLM and regression results combined, indicated fibrinogen concentration and rate of clot formation (slope) had the strongest association with Lp(a); clot density associated positively with both Lp(a) and LDL-C; time to clot formation associated negatively with ApoB; and CLT demonstrated strong positive associations with both ApoB and LDL-C, while its association with Lp(a) was fibrinogen concentration dependent. CONCLUSION: These findings suggest that ApoB and the lipoproteins carrying it contribute to prothrombotic clot properties in Africans on epidemiological level and highlight potential novel prothrombotic roles for these (apo)lipoproteins to be considered for the development of targeted therapeutic approaches to address thrombotic conditions related to clot properties.

6-methylcoumarin/miR-122 suppresses hepatic Sortilin-mediated ApoB-100 secretion to attenuate aortic atherosclerosis.

This study aimed to investigate the effects of hepatic microRNA-122 (miR-122) on Sortilin-mediated apolipoprotein B100 (apoB-100) secretion, and on aortic lipid deposition and atherosclerosis (AS) lesions and to clarify the antiatherosclerotic mechanism of 6-methylcoumarin (6-MC) via the modulation of miR-122. Bioinformatics analysis revealed that miR-122 was putatively overexpressed in a liver-specific manner and was downregulated in steatotic livers. miR-122 was shown to suppress the expression of Sortilin by complementarily pairing to the 3'-untranslated region (3'-UTR) of Sortilin mRNA via bioinformatics and dual-luciferase reporter assays, impeding Sortilin-mediated apoB-100 secretion from HepG2 cells. Administration of 6-MC significantly upregulated hepatocellular miR-122 levels, reducing Sortilin expression and apoB-100 secretion in HepG2 cells. The miR-122 mimic vigorously enhanced 6-MC-depressed Sortilin expression, while miR-122 inhibitor repealed the inhibitory effect of 6-MC on Sortilin expression to some extent in HepG2 cells. After internal intervention with the miR-122 precursor, and 6-MC supplementation alone or in combination with the miR-122 sponge led to the reduction in blood triglyceride (TG) levels, low-density lipoprotein-cholesterol (LDL-C) and apoB-100 and a reduction in aortic lipid deposition and AS lesions in apolipoprotein E-deficient (ApoE-/-) mice fed a high fat diet (HFD). The hepatic levels of Sortilin and apoB-100 expression were also decreased in these treated mice. In conclusion, miR-122 suppresses Sortilin expression and Sortilin-mediated apoB-100 secretion to resist circulating LDL production and aortic AS development, which is enhanced by 6-MC-upregulated miR-122 in the liver.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

APOBEC-1 Complementation Factor: From RNA Binding to Cancer.

BACKGROUND: APOBEC-1 complementation factor (A1CF) and Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-1 (APOBEC-1) constitute the minimal proteins necessary for the editing of apolipoprotein B (apoB) mRNA in vitro. Unlike APOBEC-1 and apoB mRNA, the ubiquitous expression of A1CF in human tissues suggests its unique biological significance, with various factors such as protein kinase C, thyroid hormones, and insulin regulating the activity and expression of A1CF. Nevertheless, few studies have provided an overview of this topic. OBJECTIVE: We conducted a literature review to describe the molecular mechanisms of A1CF and its relevance to human diseases. METHOD: In the PubMed database, we used the keywords 'A1CF' and 'APOBEC-1 complementation factor' to collect peer-reviewed articles published in English from 2000 to 2023. Two authors independently reviewed the articles and reached the consensus. RESULT: After reviewing 127 articles, a total of 61 articles that met the inclusion criteria were included in the present review. Studies revealed that A1CF is involved in epigenetic regulation of reproductive cells affecting embryonic development, and that it is closely associated with the occurrence of gout due to its editing properties on apoB. A1CF can also affect the process of epithelial-mesenchymal transition in renal tubular epithelial cells and promote liver regeneration by controlling the stability of IL-6 mRNA, but no influence on cardiac function was found. Furthermore, increasing evidence suggests that A1CF may promote the occurrence and development of breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, endometrial cancer, and glioma. CONCLUSION: This review clarifies the association between A1CF and other complementary factors and their impact on the development of human diseases, aiming to provide guidance for further research on A1CF, which can help treat human diseases and promote health.

Diagnostic Value of Serum Apolipoprotein B100 Combined With Hippocampal Volume in Alzheimer's Disease.

PURPOSE: To explore the diagnostic value of serum apolipoprotein B100 (Apo B100) combined with hippocampal volume in Alzheimer's disease (AD). METHODS: A total of 59 AD patients and 59 healthy subjects were selected. The Mini-Mental State Examination (MMSE) was used for neuropsychological assessment. Blood glucose and serum lipid levels were detected by biochemical analyzer. Polymerase chain reaction (PCR) was used to detect apolipoprotein E (Apo E) ε3/ε4 genotypes in the plasma. Hippocampal volume was calculated using Slicer software. Independent-sample t test or Mann-Whitney U test were used to compare the levels of various indicators between the two groups. Spearman's correlation analysis was used to analyze the correlation between each level. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to compare the diagnostic efficacy of individual and combined detection of serum Apo B100 levels and hippocampal volume in AD. RESULTS: Compared with the healthy control group, the levels of serum total cholesterol (TC), low-density lipoprotein (LDL), Apo B100, and plasma Apo E ε3/ε4 were higher in the AD group, and serum high-density lipoprotein (HDL) level was lower in the AD group (both p < 0.05). The hippocampal volume in the AD group was lower than in the control group (p < 0.01). The serum Apo B100 level was negatively correlated with MMSE score (r = -0.646), whereas hippocampal volume was positively correlated with MMSE score (r = 0.630). ROC curve analysis showed that the AUC of the combined serum Apo B100 level and hippocampal volume for AD was higher than that of either alone (AUC = 0.821, p < 0.01). CONCLUSION: Serum Apo B100 level is elevated, and the hippocampal volume is reduced in AD patients. The combined detection of the two has a higher diagnostic efficiency for AD than other alone and has the potential to become an important indicator for the diagnosis of AD in the future.

Association between 35 blood and urine biomarkers and oral leukoplakia: a two-sample Mendelian randomization study.

Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association.

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

Low prevalence of testing for apolipoprotein B and lipoprotein (a) in the real world.

Objective: Apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]) are predictors of cardiovascular disease (CVD) risk; therefore, current recommendations for CVD risk assessment and management advocate that patients receive testing for ApoB and Lp(a) in addition to the standard lipid panel. However, US guidelines around ApoB and Lp(a) testing have evolved over time and vary slightly by expert committee. The objective of this analysis was to estimate the number of insured individuals in the USA who received any component of a lipid test, or ApoB and/or Lp(a) testing, during 2019. Methods: We conducted a cross-sectional analysis to estimate the prevalence of any component of a lipid test, ApoB, and/or Lp(a) in the USA using four different claim data sources (including Medicaid, Medicare, and commercially insured enrollees). Prevalence estimates were age-, sex-, payor-, and region-standardized to the 2019 US Annual Social and Economic Supplement of the Current Population Survey. We also described the clinical profile of patients who received lipid testing between 2019 and 2021 (cohort analysis) in Optum claims database. Enrollees were grouped into four non-mutually exclusive cohorts based on their completion of any component of the lipid panel, ApoB, Lp(a), or ApoB and Lp(a). Results: In the prevalence cohort, over a third (38 %) of insured adults in the USA underwent testing for any component of a lipid panel in 2019. This proportion was higher for individuals aged ≥65 years compared to younger adults (62% vs 31 %). The proportion of ApoB and Lp(a) testing represented only <1 % of testing for any component of a lipid panel. In the cohort analysis, we found that lipid testing increased with age and comorbidities. Conclusion: These data should be considered by guideline-issuing agencies and organizations to develop education campaigns encouraging more frequent use of tests beyond the standard lipid panel.

It is time to address the contribution of cholesterol in all apoB-containing lipoproteins to atherosclerotic cardiovascular disease.

On average, LDL particles are the most populous lipoprotein in serum under fasting conditions. For many reasons, it has been the primary target of lipid-lowering guidelines around the world. In the past 30 years, we have witnessed remarkable changes in each iteration of dyslipidaemia guidelines, with LDL-cholesterol (LDL-C) targets becoming lower and lower among patients at high and very high risk for atherosclerotic cardiovascular disease (ASCVD). The world over, goal attainment rates are low, and hence, ASCVD prevalence remains unacceptably high. Inadequate LDL-C lowering is a major issue in contemporary cardiovascular (CV) medicine. Another issue that vexes even the most astute clinician is that of 'residual risk', meaning the excess risk that remains even after LDL-C is appropriately reduced. In recent years, an important new component of residual risk has emerged: triglyceride-enriched lipoproteins or remnant lipoproteins. These precursors to LDL particles can assume outsized importance among patients with derangements in triglyceride metabolism (e.g. genetic variants, insulin resistance, and diabetes mellitus) and may be more atherogenic than LDL species. Consequently, to reduce total risk for acute CV events, the time has come to include the entire spectrum of apoB-containing lipoproteins in approaches to both risk evaluation and treatment.