Zhenyan Fu

Background: Ischemic heart disease (IHD) is a major cause of death and disability, is consistent with modifiable factors like poor diet, inactivity, and smoking, as well as non-modifiable ones such as age and genetics. A diet high in sodium (DHIS) and kidney dysfunction (KD) significantly contribute to IHD by increasing blood pressure and promoting vascular damage. This study examines IHD burden due to DHIS and KD in G20 countries from 1990 to 2021, highlighting disparities and the need for targeted public health interventions. The findings aim to guide effective policies and improve cardiovascular health outcomes globally. Method: This study uses data from the GBD 2021 database to analyze the global burden of IHD attributable to DHIS and KD in 1990 and 2021. Descriptive analysis examines the distribution of IHD across genders, age groups, regions, and countries, using age-standardized rates (ASR) and uncertainty intervals. Trend analysis calculates the annual percentage change (EAPC) in IHD-related mortality and disability. Decomposition analysis evaluates the contributions of age structure, population growth, and epidemiologic changes. Forecasting is done through the Auto-Regressive Integrated Moving Average (ARIMA) and exponential smoothing (ES) models, with Bayesian age-period-cohort models projecting future IHD burdens through 2050. Result: In 2021, IHD attributable to DHIS and KD caused significant disease burden in G20 countries. Deaths and DALYs due to IHD attributable to DHIS increased by 83.8% and 71.4%, respectively, while those attributable to KD rose by 61.8% and 52.3% from 1990 to 2021. Despite declines in age-standardized mortality and DALY rates, regional and sex disparities persisted, with higher burdens in males and low-SDI regions. Ageing and population growth were primary drivers of increased deaths and DALYs. Projections indicate rising deaths and DALYs, but continued declines in age-standardized rates by 2050 under ARIMA and ES models. Conclusion: This study highlights the urgent need for targeted interventions to address the growing IHD burden attributable to DHIS and KD in G20 nations, emphasizing primary prevention, equitable healthcare, and tailored strategies to mitigate future cardiovascular risks effectively.

Background: Inflammatory infiltration constitutes a fundamental pathophysiological mechanism in myocardial ischemia-reperfusion (IR) injury, characterized by its role in initiating tissue damage, amplifying pathological inflammatory cascades, and exacerbating structural and functional impairment of the myocardium. Integrated transcriptomic and metabolomic analysis identified the metabolite itaconic acid as a potential key regulator in IR injury. Therefore, we assessed the effect of its derivative, 4-octyl itaconate (4-OI), on inflammatory infiltration in a mouse model of IR injury. Methods: Following establishment of a myocardial IR model, tissue samples from the infarct border zone were harvested for transcriptomics and wide-target metabolomic sequencing. Bioinformatics methods were used to analyze the transcriptomics and metabolomics results separately and to perform a joint analysis. Molecular docking and molecular dynamics modeling were employed to explore proteins bound to itaconic acid. Following intragastric administration of 4-OI to myocardial IR mice, echocardiography was performed. Plasma levels of interleukin-4 (IL4), interleukin10 (IL10), cardiac troponin T (cTnT), and creatine kinase-myocardial band (CKMB) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial inflammatory infiltration was evaluated by hematoxylin and eosin Staining (HE staining), while inflammatory marker expression associated with macrophages was evaluated by immunohistochemical staining for inducible nitric oxide synthase (iNOS) and immune responsive gene 1 (IRG1). Macrophage heterogeneity was further assessed by immunofluorescence co-localization staining for F4/80, CCR2, and CD206. Additionally, mRNA expression levels of Interleukin-1 beta (Il1b), Tumor Necrosis Factor-alpha (Tnfa), Il4, and Il10 in myocardial tissue were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: Integrated transcriptomic and metabolomic analysis identified itaconic acid as a potential metabolite modulating myocardial IR injury. Preliminary molecular docking analysis suggested possible in silico interactions between itaconic acid and Pla2g2d, Lcn2, and Gpr55 proteins, which require further experimental validation. A derivative of itaconic acid, 4-OI, significantly ameliorated myocardial IR injury in mice, reduced inflammatory infiltration, decreased iNOS-associated staining, and modestly increased Arg1-associated staining in the infarct border zone. This treatment was also accompanied by differences in macrophage marker-defined populations, reflected by fewer F4/80 ⁺ CCR2 ⁺ and more F4/80 ⁺ CD206 ⁺ cells in the injured myocardium.

Background: Red meat, particularly beef, is rich in saturated fatty acids, which are major precursors for triglyceride (TG) synthesis. However, the association between red meat consumption and cardiometabolic risk remains controversial, and high-quality evidence is still limited. Therefore, this study aims to systematically evaluate the relationship between beef intake and TG levels in adult populations, as well as to explore potential causal links between them. Method: This study integrated data from the National Health and Nutrition Examination Survey (NHANES, 2007–2018) and the “Comprehensive Health Check-up Project” (2024) in Urumqi, China, including 2,134 and 1,974 adults, respectively, for cross-sectional analysis. A multivariable stepwise regression model was used to assess the association between beef intake (analyzed as both continuous and quartile variables) and TG levels. RCS analysis was performed to explore nonlinear relationships, and subgroup analyses were conducted to identify population-specific associations. Additionally, two-sample Mendelian randomization analysis was applied to infer a potential causal relationship from a genetic perspective. Result: Cross-sectional analyses showed that after full adjustment for confounding factors, each 100 g/d increment in beef intake was associated with an average increase in TG levels of 0.11 mmol/L in U.S. adults and 0.12 mmol/L in Chinese adults. RCS analysis revealed that the risk of hypertriglyceridemia tended to rise when beef intake exceeded approximately 100 g/d. Mendelian randomization analysis further supported a causal link, demonstrating that genetically predicted higher beef intake was associated with an approximately 2.1-fold increased risk of hypertriglyceridemia (pooled OR = 2.13, 95% CI: 1.63–2.79). Conclusion: Higher beef intake (particularly > 100 g/d) is significantly associated with elevated TG levels, and this association may reflect a genetically mediated causal relationship.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs widely used in clinical practice for the treatment of dyslipidemia. However, real-world data regarding their long-term neurological safety and tolerability in large populations remain incomplete. Therefore, we utilized the FAERS and real-world data from Chinese patients to jointly analyze the association between PCSK9 inhibitors and adverse drug events (ADEs) related to nervous system disorders. Methods: A disproportionality analysis was performed on all ADEs associated with PCSK9 inhibitors in the FAERS database from the third quarter of 2015 to the second quarter of 2025. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were employed to comprehensively evaluate and screen for statistically significant positive signals of adverse drug reactions related to nervous system disorders. These signals were further validated using follow-up data from 1,203 Chinese coronary heart disease (CHD) patients treated with PCSK9 inhibitors. Results: A total of 173,622 reports involving at least one PCSK9 inhibitor were identified in FAERS. Statistically significant positive ADEs signals associated with PCSK9 inhibitors included: Memory Impairment [ n = 1,346, ROR = 1.48 (95% CI 1.4–1.56), IC = 0.55 (IC025 0.47), Bonferroni- p = 2.2028e ⁻⁴² ], Amnesia [ n = 452, ROR = 1.25 (95% CI 1.14–1.38), IC = 0.32 (IC025 0.18), Bonferroni- p = 0.0097], Head Discomfort [ n = 190, ROR = 1.46 (95% CI 1.26–1.68), IC = 0.54 (IC025 0.32), Bonferroni- p = 0.0013], Sinus Headache [ n = 65, ROR = 2.38 (95% CI 1.86–3.04), IC = 1.23 (IC025 0.84), Bonferroni- p = 1.0944e ⁻⁰⁸ ], and Carotid Artery Occlusion [ n = 56, ROR = 3.08 (95% CI 2.36–4.02), IC = 1.59 (IC025 1.16), Bonferroni- p = 3.2089e ⁻¹⁴ ]. Analysis of real-world follow-up data from Chinese CHD patients revealed that, compared to CHD patients not using any PCSK9 inhibitors, those treated with PCSK9 inhibitors exhibited significantly higher incidences of Memory Impairment ( p < 0.0001) and Head Discomfort ( p = 0.0027). Conclusion: Our study highlights that it is essential to recognize the potential risks of adverse neurological reactions, particularly Memory Impairment and Head Discomfort. These findings may assist healthcare professionals in providing more precise and individualized treatment plans.

The bempedoic acid plus ezetimibe fixed-dose combination (BAPEFC) is a novel lipid-lowering agent that was successively marketed in regions such as the United States and the European Union in 2020. It significantly reduces low-density lipoprotein cholesterol through a dual mechanism of inhibiting adenosine triphosphate-citrate lyase and Niemann-Pick C1-like 1. Although clinical trials have confirmed its efficacy, its long-term safety in the real world requires further evaluation. All adverse event reports related to BAPEFC from the first quarter of 2020 to the first quarter of 2025 were extracted from the FDA Adverse Event Reporting System (FAERS) database. After data standardization, a comprehensive evaluation of adverse reaction signals was performed using the reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Subgroup analyses by sex and age were further conducted for newly identified adverse drug reactions. A total of 875 reports involving at least 1 BAPEFC agent were identified in FAERS. The preferred term with the highest number of reports was arthralgia (n = 103), while the strongest positive signal was for tendon discomfort (n = 3, ROR = 135.27, proportional reporting ratio = 135.03, information component = 7.06, empirical Bayes geometric mean = 133.36). At the system organ class level, musculoskeletal and connective tissue disorders had the highest ROR value (ROR = 6.02, 95% confidence interval [CI]: 5.46–6.63). The newly identified signal for “Blood Triglycerides Increased” showed statistically significant ROR signals in both male and female subgroups (ROR = 36.59 [95% CI: 15.16–88.32] vs ROR = 34.78 [95% CI: 15.57–77.67]), and the adjusted Bonferroni- P values were statistically significant (Bonferroni- P < .0001). Subgroup analysis of the combined data for the newly identified “Pancreatitis” and “Pancreatitis Acute” showed statistically significant ROR signals in both the non-elderly subgroup (P values were statistically significant (Bonferroni- P = .0003 vs Bonferroni- P = .0106). Based on the FAERS database, this study provides the first comprehensive and systematic analysis of adverse drug events associated with BAPEFC. It newly identifies several adverse drug reactions not mentioned in the prescribing information, such as blood triglycerides increased, pancreatitis, and pancreatitis acute, thereby offering evidence for clinical monitoring and identification of potential risks associated with BAPEFC.

Accurate individual risk assessment is crucial for guiding and improving the prevention of atherosclerotic cardiovascular disease (ASCVD). Existing predict

Numerous studies have confirmed that the cumulative exposure of low-density lipoprotein cholesterol (LDL-C) is closely related to the occurrence of adverse

Objective: This study aimed to evaluate the prognostic value of the Chinese Visceral Adiposity Index (CVAI) for all-cause mortality in the high-risk population with coexisting type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD). Results: Over a median 26-month follow-up among 442 patients, 194 deaths occurred. The highest CVAI tertile (T3) exhibited a significantly elevated mortality risk (adjusted hazard ratio [HR] = 2.806, 95% confidence interval [CI] 1.848–4.261, P < 0.001), demonstrating a linear dose-response relationship. CVAI provided significant incremental predictive value beyond left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Subgroup analysis revealed a significant association in patients with LVEF < 40% but not in those with LVEF ≥ 40% (P for interaction = 0.049).

Background: To analyze the prevalence and epidemiological characteristics of dyslipidemia among adults of different genders in Xinjiang, China, providing a basis for promoting ideal lipid management among the Uyghur population. Methods: In this retrospective study, we included 7,646 Uyghur adults from the 2021 physical examination data in Hotan, Xinjiang, and followed up with all participants in 2023 for analysis. Participants completed lifestyle and medical history questionnaires and underwent lipid profiling. Dyslipidemia was defined according to the 2023 Chinese guidelines for lipid management. Group differences were analyzed using t-tests, ANOVA, and chi-square tests, the trend test for ordered categorical variables was conducted using univariate linear regression, and multivariable logistic regression was performed to explore risk factors for dyslipidemia. Results: In 2023, the average levels of waist circumference, fasting glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C among Uyghur men and women, as well as the prevalence of diabetes, increased compared to 2021, with significant statistical differences within the same gender groups (P < 0.001). The primary types of dyslipidemia among Uyghur adults were low HDL-C. After age and gender standardization, the overall standardized prevalence of high low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia, and low HDL-C showed a downward trend, with a more pronounced decrease among men. The prevalence of hypercholesterolemia and high non-HDL-C increased from 2021, with a greater increase among women. In 2023, the standardized prevalence rates of hypercholesterolemia, high LDL-C, low HDL-C, hypertriglyceridemia, and high non-HDL-C were higher in women than in men. Multivariable logistic regression adjusted for multiple factors indicated that higher educational attainment (OR 1.992; 95% CI [1.042–3.808]; P = 0.037), overweight (OR 1.303; 95% CI [1.085–1.566]; P = 0.005), obesity (OR 1.520; 95% CI [1.226–1.886]; P = 0.000), and central obesity (OR 1.013; 95% CI [1.006–1.021]; P = 0.001) were associated with dyslipidemia in Uyghur men, while in Uyghur women, dyslipidemia prevalence was mainly related to obesity (OR 1.549; 95% CI [1.261–1.902]; P = 0.000) and central obesity (OR 1.009; 95% CI [1.002–1.016]; P = 0.01). Conclusion: The primary forms of dyslipidemia among Uyghur adults include low HDL-C levels. The prevalence of high LDL-C, hypertriglyceridemia, and low HDL-C is showing a declining trend, particularly among men. In contrast, the prevalence of hypercholesterolemia and high non-HDL-C is increasing more significantly among women. In men, risk factors for dyslipidemia include higher educational attainment, being overweight, obesity, and central obesity. In women, the prevalence of dyslipidemia is mainly associated with obesity and central obesity.

Background: Serum ferritin (SF) levels are associated with metabolic syndrome and dyslipidemia. However, the association between SF and atherogenic lipid profiles in high-altitude living populations remains unclear. Methods: In 2021, a cross-sectional study was conducted on adult Tajik individuals residing in Tashkurgan Tajik Autonomous County (average altitude 3,100 meters). Demographic information and anthropometric measurements were collected in local clinics. Fasting blood samples were analyzed using a Beckman AU-680 Automatic Biochemical analyzer at the biochemical laboratory of Fuwai Hospital. Univariate linear regression analyses were used to explore the association between SF and atherogenic lipid levels. Subgroup analysis was used based on gender and different high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) levels. The association between higher SF quartiles and different kinds of dyslipidemia were analyzed by logistic regression. Results: There were 1,703 participants in total, among which 866 (50.9%) being men. The mean ages of male and female participants were similar (41.50 vs. 42.38 years; P = 0.224). SF levels were significantly correlated with total cholesterol (TC) (Beta = 0.225, P < 0.001), low-density lipoprotein cholesterol (LDL-C) (Beta = 0.197, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (Beta = −0.218, P < 0.001), triglycerides (TG) (Beta = 0.332, P < 0.001), and small dense LDL-C (sdLDL-C) (Beta = 0.316, P < 0.001), with the exception of lipoprotein (a) (Lp(a)) (Beta = 0.018, P = 0.475). SF was significantly correlated with LDL-C and HDL-C in women, and correlated with TC, TG, and sdLDL-C levels in both men and women in different inflammatory conditions. Elevated SF levels was significantly correlated with high TC (OR: 1.413, 95% CI [1.010–1.978]), high TG (OR: 1.602, 95% CI [1.299–1.976]), and high sdLDL-C (OR: 1.631, 95% CI [1.370–1.942]) in men and high TC (OR: 1.461, 95% CI [1.061–2.014]), high LDL-C (OR: 2.104, 95% CI [1.481–2.990]), low HDL-C (OR: 1.447, 95% CI [1.195–1.752]), high TG (OR: 2.106, 95% CI [1.454–3.050]), and high sdLDL-C (OR: 2.000, 95% CI [1.589–2.516]) in women. After adjusting for potential confounders, elevated SF levels continue to be correlated with high TG in male (OR: 1.382, 95% CI [1.100–1.737]) and female (OR: 1.677, 95% CI [1.070–2.628]) participants. In both young and middle-aged subgroups, the associations between SF and TG, TC, HDL-C, LDL-C, and sdLDL-C were still significant. Conclusions: SF was closely related to atherogenic lipid profiles, especially with regard to TG in high-altitude populations. This association cannot be attributed to its role as an inflammation marker.