Abstract:Dyslipidemia represents a crucial risk factor for atherosclerotic cardiovascular diseases (ASCVD). Currently, intervention strategies guided by routine blood lipid testing in clinical practice still have notable limitations in reducing its incidence risk. Lipoprotein subfractions hold great potential for uncovering residual risks, highlighting the urgent need to address the following key questions:①How to utilize lipoprotein and subfraction testing to identify and control lipid-related residual risks; ②How to carry out research centered on fine lipoprotein phenotypes to uncover their role in predicting ASCVD risk, discover new risk markers, and identify novel targets for lipid-lowering and anti-atherosclerotic treatment; ③How to facilitate the prompt clinical implementation of lipoprotein and subfraction testing to further improve the prevention, diagnosis, and treatment of ASCVD. Targeted breakthroughs in these issues will contribute to comprehensively improving the clinical prevention, treatment, and research levels of lipoprotein metabolism disorders and ASCVD in China, thereby reducing the incidence risk and disease burden.

Abstract:Lipoprotein(a) [Lp(a)] is a low density lipoprotein(LDL)-like particle formed by the covalent bonding of apolipoprotein B100(ApoB100) and apolipoprotein A(ApoA). Recent studies have shown that elevated Lp(a) levels are an independent risk factor for cardiovascular diseases. At the same time, vascular calcification contributes to increased mortality from cardiovascular diseases and a higher risk of cardiovascular events. Vascular calcification is an active, highly regulated pathological process characterized by abnormal deposition of calcium-phosphate salts in the vascular wall. It involves the transdifferentiation of vascular smooth muscle cells(VSMC) into osteogenic/chondrogenic lineages, leading to the accumulation of calcium-phosphate salts in the arterial wall. Existing evidence indicates that Lp(a) promotes the initiation and progression of vascular calcification through multiple pathways. This review aims to summarize the basic structure of Lp(a) and its mechanisms in promoting vascular calcification, as well as to explore its association with vascular calcification and potential therapeutic advances.

Abstract:Aim To explore the correlation between hyperlipoproteinemia (a) and levels of inflammatory factors and the severity of coronary artery lesions. Methods A total of 462 patients undergoing coronary angiography were stratified into a high lipoprotein(a)[Lp(a)] group (≥75 nmol/L) and a normal Lp(a) group (＜75 nmol/L). Clinical data, blood lipid profile, Gensini score, and levels of 12 inflammatory factors from patients were collected. Spearman correlation analysis and Logistic regression model were used to evaluate the correlation between high Lp(a) levels and plasma levels of inflammatory factors and the severity of coronary heart disease. Results Compared with the normal Lp(a) group, the high Lp(a) group showed significant increases in the levels of 9 types of inflammatory factors, such as interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-5 (IL-5) (all P＜0.05), as well as a significant increase in the proportion of patients of coronary heart disease and high Gensini scores (both P＜0.05). Spearman correlation analysis and Logistic regression analysis showed that high levels of Lp(a) were positively correlated with levels of IFN-γ, IL-4, IL-5, interleukin-6 (IL-6), interleukin-12P70 (IL-12P70), interleukin-1β (IL-1β), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) (all P＜0.05). Multivariate Logistic regression analysis showed that high levels of Lp(a) were independent risk factors for coronary heart disease (OR＝2.3,5%CI:1.548～4.060) and high Gensini scores (OR＝2.2,5%CI:1.332～3.344). Conclusion Hyperlipoproteinemia(a) can lead to elevated levels of multiple inflammatory factors, thereby increasing the risk of coronary heart disease and worsening the severity of coronary heart disease.

Abstract:Aim To investigate the correlation between lipoprotein(a)[Lp(a)] and high thrombus burden in patients with new-onset ST-segment elevation myocardial infarction (STEMI) and its predictive value. Methods The retrospective study included 281 patients with acute STEMI and left anterior descending artery lesions admitted to the Chest Pain Center of Yancheng No.1 People's Hospital from 2021 to 2023 due to persistent chest pain. Thrombus burden was graded using the TIMI thrombus classification:grades 1～3 as low thrombus burden (LTB) group and grades 4～5 as high thrombus burden (HTB) group. Baseline clinical data and laboratory results were collected and compared between the two groups. Univariate and multivariate binary Logistic regression analysis were performed to identify risk factors for HTB.ROC curves were plotted to evaluate the predictive value of Lp(a) for HTB in STEMI patients. Results Compared with the LTB group, the HTB group had a lower proportion of male patients and higher levels of white blood cell count (WBC), neutrophil count, neutrophil-to-lymphocyte ratio (NLR), fibrin degradation products (FDP), D-dimer (DD), total bilirubin (TB), indirect bilirubin (IB), and Lp(a) (P＜0.05). The results of multivariate Logistic regression analysis showed that elevated levels of serum Lp(a) and TB, as well as male gender, were independent risk factors for HTB in new-onset STEMI patients (P＜0.05). Based on the results of multivariate regression analysis, a receiver operating characteristic (ROC) curve was plotted to determine its cut-off value. When the Lp(a) threshold was 288.2 mg/L, the sensitivity was 0.560, the specificity was 0.837 (area under the curve(AUC)=0.5,5%CI:0.673～0.798, P＜0.001). The ability of serum Lp(a) level combined with TB to predict HTB in new-onset STEMI patients was significantly improved, with AUC value of 0.787. Conclusion Serum Lp(a) level is an independent risk factor for HTB in patients with new-onset STEMI, and there is a significant positive correlation between the two. Furthermore, Lp(a) level exhibits significant predictive value for the occurrence of HTB events in STEMI patients. It is imperative to control Lp(a) levels at the primary prevention level.

Abstract:Aim To analyze the vertical auto profile (VAP) method and formula method to determine remnant lipoprotein cholesterol (RLPC), and compare the clinical value of the two methods in the diagnosis of diabetic atherosclerosis. Methods From June 2022 to June 2024, diabetes patients from the Endocrinology Department of Ningbo Yinzhou Hospital of Traditional Chinese Medicine were selected as the study subjects, including 107 patients with diabetes complicated with carotid plaque, who were set as the diabetic plaque group; there were 103 patients with diabetes without carotid plaque, and they were set as diabetic non-plaque group. Meanwhile, 102 healthy individuals who came to the hospital for physical examinations during the same period were selected as the normal control group. The RLPC level in peripheral blood of each group was measured by VAP method and formula method (RLPCVAP and RLPC_formula). First, methodogical comparisons of the two methods were performed, and then the area under the ROC curve (AUC) of RLPCVAP and RLPC_formula for diagnosing carotid plaque in diabetes was drawn and calculated. Results The coefficient of variation of peripheral blood RLPC detected by VAP method was lower than that of formula method. The negative rate of peripheral blood RLPC detected by formula method was 3.21%, while RLPC detected by VAP method did not show negative values.There was a significant positive correlation between peripheral blood RLPCVAP and RLPC_formula (P＜0.01). The levels of RLPCVAP in diabetic plaque group and diabetic non-plaque group was significantly lower than those of RLPC_formula (P＜0.01). The AUC value of peripheral blood RLPCVAP in the diagnosis of carotid plaque in diabetes was significantly greater than that of RLPC_formula. Conclusion The methodological performance of VAP method for measuring peripheral blood RLPC is superior to formula method. VAP method can accurately detect the level of RLPC, which is significantly superior to the RLPC results calculated by formula method in the clinical efficacy of diagnosing diabetic atherosclerosis.

Abstract:Aim To investigate whether hydrogen sulfide (H₂S) alleviates endothelial cell hypoxia/reoxygenation (H/R) injury by upregulating the expression of WD repeat protein 26 (WDR26).Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro under hypoxic conditions (5%O₂,5%CO₂) for 16 h followed by reoxygenation (20%O₂,5%CO₂) for 3 h to induce H/R injury. HUVEC models with WDR26 gene knockdown and overexpression were constructed using lentiviral transfection technology. The content of malondialdehyde (MDA) was detected by colorimetric method and the cell survival rate was detected by CCK-8; the content of reactive oxygen species (ROS) in the cells was detected by immunofluorescence method; the expressions of WDR26 and apoptosis-related proteins were detected by Western blot; the contents of lactate dehydrogenase (LDH), intercellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) in the cultured supernatant were detected by ELISA. Results The exogenous H₂S donor NaHS could increase the survival rate of H/R endothelial cells, reduce ROS and MDA contents, and thereby alleviating endothelial cell damage and oxidative stress response (P＜0.05 or P＜0.01). NaHS could increase the expression of WDR26 protein (P＜0.05). Overexpression of WDR26 could increase the survival rate of H/R endothelial cells, reduce LDH content, decrease the expression of apoptosis related proteins Caspase-3, p53 and Bax, thereby reducing endothelial cell damage and alleviating cell apoptosis; on the contrary, inhibiting WDR26 expression would result in the opposite effect (P＜0.05 or P＜0.01). NaHS and/or overexpression of WDR26 could increase cell survival rate, reduce LDH, ICAM-1 and ET-1 in the cultured supernatant, and thereby improve endothelial cell function; overexpression/inhibition of WDR26 could enhance/weaken its protective effect (all P＜0.05). Conclusion H₂S can alleviate H/R injury of endothelial cells, and its effect is partly dependent on upregulation of WDR26.

Abstract:Aim To analyze the levels and correlations of serum HOX transcript antisense RNA (HOTAIR), serine/arginine-rich splicing factor 1(SRSF1), mammalian target of rapamycin (mTOR) pathway markers phosphorylated eukaryotic translation initiation factor 4E binding protein 1/eukaryotic translation initiation factor 4E binding protein 1 (p4EBP1/4EBP1) ratio, NOD-like receptor protein 3 (NLRP3) inflammasome, and systemic inflammatory response index (SIRI) in patients with coronary heart disease (CHD), and to evaluate their predictive value for the severity of coronary stenosis. Methods During the period from January to December 2024, a total of 120 CHD patients (60 mild and 60 severe stenosis cases) and 60 healthy controls who received care in the Cardiology Department of the Second Hospital of Shanxi Medical University were recruited. Serum level of HOTAIR was measured by RT-qPCR, while SRSF1,4EBP1, p4EBP1, and NLRP3 levels were measured by enzyme-linked immunosorbent assay(ELISA). SIRI was calculated from the neutrophil, monocyte, and lymphocyte counts, the severity of coronary stenosis was evaluated using the Gensini scoring system. The efficacy of these biomarkers was assessed by Spearman correlation analysis, ordinal Logistic regression, and receiver operating characteristic (ROC) curve analysis. Results ①In severe stenosis group and mild stenosis group, serum levels of HOTAIR, SRSF1, p4EBP1/4EBP1 ratio, and SIRI were higher than those in healthy control group (all P＜0.001). In contrast, NLRP3 level increased only in the severe stenosis group(P＜0.001). ②Spearman correlation analysis revealed significant positive correlations between all measured biomarkers and the severity of coronary stenosis, as well as among the biomarkers themselves (all P＜0.001). NLRP3 level was positively correlated with stenosis severity and other biomarkers (P＜0.05), but not with the p4EBP1/4EBP1 ratio (P＞0.05). ③Ordinal Logistic regression analysis showed elevated levels of these biomarkers were all independent risk factors for the severity of coronary stenosis (all P＜0.05). ④ROC curve analysis demonstrated that all biomarkers had significant predictive efficacy for severe coronary stenosis (all P＜0.001), and the predictive ability of HOTAIR, SRSF1, and SIRI levels was significantly higher than that of the p4EBP1/4EBP1 ratio and NLRP3 level. Conclusion Serum levels of HOTAIR, SRSF1, mTOR pathway markers, NLRP3, and SIRI in patients with CHD show a coordinated elevation and are closely associated with the severity of coronary stenosis. HOTAIR, SRSF1, and SIRI demonstrate high predictive value for severe coronary stenosis, offering new insights into the inflammatory mechanisms and noninvasive diagnosis of CHD.

Abstract:Aim To explore the correlation between the standardized F wave latency and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy (DPN). Methods120 DPN patients who visited our hospital from March 2022 to May 2023 were selected as the study subjects, and were divided into thickened group (n＝57) and non-thickened group (n＝63) based on CIMT. The general information and standardized F-wave latency of two groups of patients were compared, and multivariate linear regression analysis was used to investigate the relationship between standardized F-wave latency and CIMT. Restricted cubic spline model was used to analyze the dose-response relationship between standardized F-wave latency and CIMT thickening risk, and ROC curve was used to analyze the predictive value of standardized F-wave latency for CIMT thickening. According to the degree of DPN, the patients were divided into severe group (n＝42) and non severe group (n＝78). Multivariate Logistic regression was used to analyze the risk factors of severe DPN, and subgroup analysis was conducted on severe DPN in different CIMT. Results The minimum, average, and maximum values of standardized F-wave latency were higher in the thickened group than those in the non-thickened group, and the difference between the two groups was statistically significant (P＜0.05). There was a non-linear dose-response relationship between the minimum, average, and maximum values of standardized F-wave latency and the risk of CIMT thickening (P＜0.05). As the minimum, average, and maximum values of standardized F-wave latency increased, the risk of CIMT thickening increased. The minimum, average, and maximum values of standardized F-wave latency were positively correlated with CIMT (P＜0.05). Long duration of T2DM and elevated standardized F-wave latency were independent risk factors for severe DPN (P＜0.05). The overall DPN severity was more severe in the thickened group, and severe DPN occured more frequently in individuals with a minimum standardized F-wave latency ≥13.12 ms, a mean standardized F-wave latency ≥17.04 ms, or a maximum standardized F-wave latency ≥19.35 ms. The minimum, average, and maximum values of standardized F-wave latency had good predictive value for CIMT thickening. Conclusion The standardized F-wave latency of DPN is closely related to CIMT. As the minimum, average, and maximum values of standardized F-wave latency increase, the risk of CIMT thickening increases, and together they affect the severity of DPN.

Abstract:Aim To explore the application value of shear wave elastography (SWE) in the quantitative evaluation of carotid elasticity in uremic patients with different left ventricular configurations. Methods A total of 139 uremic patients were classified into four groups based on different left ventricular configurations:normal geometry group (NG, n＝37), concentric remodeling group (CR, n＝37), concentric hypertrophy group (CH, n＝38), and eccentric hypertrophy group (EH, n＝27). Additionally, 40 healthy individuals were selected as the control group. General clinical data and biochemical indicators of the subjects were collected and compared. Conventional carotid ultrasound was used to assess the intima-media thickness (IMT), peak systolic velocity (PSV), and the systolic and diastolic diameters (Ds and Dd) of the left common carotid artery. The wall motion degree (ΔD) and arterial stiffness coefficient (β) were calculated. The maximum elastic modulus (ME_max), mean elastic modulus (ME_mean), and minimum elastic modulus (ME_min) of the carotid artery anterior wall intima-media were obtained using SWE. Results Compared with the control group, IMT and β were elevated in the NG group and CR group, but there were no significant differences among the three groups (P＞0.05). In contrast, IMT and β values were increased in the CH group and EH group compared with the control group, NG group, and CR group (P＜0.05). Compared with the control group, ME_max, ME_mean, and ME_min were significantly elevated in the NG group, CR group, CH group and EH group, with a progressive increase observed in the order:EH group ＞ CH group ＞ CR group ＞ NG group ＞ control group, statistically significant differences were found among all groups (P＜0.05). ME_max, ME_mean and ME_min in all groups were positively correlated with IMT, β and triglyceride (TG) (all r＞0.39, all P＜0.01). The linear regression analysis revealed a statistically significant association between different left ventricular configurations and SWE parameters in uremic patients (P＜0.05). Conclusions Uremic patients with different left ventricular configurations exhibit varying degrees of carotid artery involvement. SWE can provide quantitative and early evaluation of carotid artery elasticity in these patients.

Abstract:Aim To investigate the relationship between brachial-ankle pulse wave velocity (BaPWV) and the risk of chronic kidney disease (CKD) in young and middle-aged people. Methods Using a prospective cohort study design, the young and middle-aged population (n＝5 835) of Kailuan Group workers who participated in the BaPWV survey for the first time during their health check-up in 2010 were selected for the study. The participants were divided into four groups according to the quartiles of BaPWV level. Follow-up was performed every two years, with new-onset CKD, death or the end of follow-up (31 December 2020) as the follow-up endpoints. The association between BaPWV and the risk incident CKD in young and middle-aged people was analyzed. Results (1) The study population consisted of 4 029 (69.05%) males and 1 806 (30.95%) females aged (48.09±6.30) years. (2) New-onset CKD occurred in 903 patients during follow-up, with a median follow-up time of 9.47 (5.6,0.18) years. 159 (10.91%) patients in the group Q1 had CKD, with an incidence density of 11.56 (9.9,3.50)/1 000 person-years; 195 (13.36%) patients in the group Q2 had CKD, with an incidence density of 14.31 (12.3,6.46)/1 000 person-years; 248 (17.00%) patients in group Q3 developed CKD with an incidence density of 18.50 (16.3,0.95)/1 000 person-years; 301 (20.63%) patients in group Q4 developed CKD with an incidence density of 23.41 (20.1,6.21)/1 000 person-years.The cumulative incidence of new-onset CKD in patients in the four groups gradually increased with increasing BaPWV levels, and all of them were statistically significant (P＜0.001). (3) The results of multifactorial Cox regression showed that compared with group Q1, the HR (95%CI) for the incidence of CKD in group Q2, Q3, Q4 were 1.08 (0.87～1.34), 1.27 (1.03～1.58), 1.44 (1.14～1.82)(P_trend＜0.001). Conclusion BaPWV is significantly associated with the risk of CKD in young and middle-aged people.

Abstract:Acute myocardial infarction is still a cardiovascular disease with high mortality. Promoting angiogenesis after infarction can promote revascularization and improve myocardial function, which is of great significance for the repair of myocardial injury. Angiogenesis after myocardial infarction starts from the infarct boundary area and extends to the necrotic infarction core, the process of angiogenesis is complex, and its mechanisms have not been fully elucidated; there are several signal transduction pathways that can regulate the process of angiogenesis, including phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), Notch signaling pathway (Notch), janus kinase/signal transducer and activator of transcription (JAK/STAT) and sonic hedgehog signaling pathway (Shh), etc. Elucidating the related mechanisms of angiogenesis after myocardial infarction through various signal transduction pathways can provide research evidence and direction for the treatment of angiogenesis after myocardial infarction. This article reviews the characteristics of angiogenesis after myocardial infarction and the related mechanisms of signal transduction pathways in angiogenesis.

Abstract:Atherosclerosis creates a hypoxic microenvironment that activates hypoxia-inducible factor-1α (HIF-1α). This factor promotes pathological angiogenesis via vascular endothelial growth factor (VEGF) induction, increasing plaque vulnerability, while simultaneously exacerbating inflammation through metabolic reprogramming of macrophages, enhanced NOD-like receptor protein 3 (NLRP3) inflammasome activity (driving interleukin-1β (IL-1β) maturation), and M1 polarization. In vascular smooth muscle cells, HIF-1α stimulates proliferation, migration, and osteogenic differentiation via VEGF autocrine signaling, macrophage migration inhibitory factor (MIF), and solute carrier family 3 member 2 (SLC3A2) pathways, accelerating vascular calcification. In vascular endothelial cell, HIF-1α amplifies oxidative stress by enhancing monocyte adhesion and forming a feedback loop with nuclear factor-κB (NF-κB), further disrupting endothelial homeostasis. This paper summarizes that HIF-1α promotes plaque instability and thrombotic risk by coordinating angiogenesis, inflammatory amplification and cellular phenotype transformation, which provides a molecular theoretical basis for targeted intervention.

Abstract:Heart failure (HF), as one of the most severe cardiovascular diseases, has shown a continuous rise in incidence in recent years. Its pathogenesis is closely associated with epigenetic regulation, among which N6-methyladenosine (m⁶A) methylation — the most common post-transcriptional epigenetic modification in the genome — plays a crucial role in the occurrence and progression of HF. This review first outlines the basic concepts of m⁶A methyltransferases, m⁶A demethylases, and m⁶A-binding proteins, as well as their roles in the pathogenesis of HF. Subsequently, it explores the potential mechanisms of m⁶A methylation in HF from aspects including autophagy, apoptosis, calcium homeostasis, and inflammatory response, aiming to provide a reference for future relevant research.