Naifeng Liu

Background: Breast cancer (BC) and atrial fibrillation (AF) represent increasing global health burdens with shared risk factors. However, their coincidence burden and global distribution among older women (≥55 years) remain unclear. Methods: This study integrated data from the Global Burden of Disease 2021 database spanning 204 countries and territories, covering incidence rates of BC and AF and exposure rates of 58 risk factors. Using a 4‐quartile classification algorithm, we divided the globe into 3 regions (consistent, BC‐dominant, and AF‐dominant area). Risk factors were screened by using machine learning models (random forest, spatial statistics, and SHAP interpretability framework). Population‐attributable fraction and a composite risk index model were generated to evaluate disease burdens and spatial risk localization of BC and AF. Results: The consistent area (80 countries, 39.60%) exhibited overlapping BC‐AF incidence, while BC‐dominant (65 countries, 32.18%) and AF‐dominant (57 countries, 28.22%) regions highlighted geographic disparities. After screening of machine learning models, 2 shared factors (smoking and alcohol use) and 2 BC‐specific factors (high body mass index and low physical activity) were included in the calculation of population‐attributable fraction, potentially reducing global BC and AF incidence by 29.05% and 11.75% after shifting these factors to theoretical minimum exposure levels. For most factors, high‐risk zones clustered in North and South America, Europe, and Oceania mainly correlate with dietary and lifestyle patterns. Conclusions: The spatial coincidence of BC and AF present a significant global health challenge. Addressing both shared and region‐specific risk factors can substantially reduce the dual burden of these diseases.

Vascular smooth muscle cells (VSMCs), which form the media layer of blood vessels, play a vital role in vascular homeostasis and remodeling. Dysfunction of VSMCs represents a key pathological basis and an important contributor to vascular diseases. Ferroptosis, an iron-dependent accumulation of lipid hydroperoxides, is a novel form of regulated cell death. VSMC ferroptosis is involved in a range of vascular diseases, such as atherosclerosis, vascular calcification, hypertension, aortic aneurysm, aortic dissection, neointimal hyperplasia, intracranial aneurysm, and pulmonary arterial hypertension. This review summarizes the current evidence, underlying potential mechanisms, and therapeutic targets of VSMC ferroptosis in vascular diseases. A deeper understanding of this process may provide therapeutic insights and help in mitigating cardiovascular risk in affected patients.

Patients with diabetes exhibit an increased susceptibility to vascular calcification, which is associated with significantly elevated risks of mortality and disability. As a new Glucagon-like peptide-1 receptor agonist, Semaglutide is primarily indicated for type 2 diabetes mellitus and obesity, while also demonstrating definitive cardiovascular protective effects. However, the effect of semaglutide on diabetic vascular calcification remains unknown. Our results demonstrated a dose-dependent reduction in calcium deposition with Semaglutide treatment, which was accompanied by downregulation of RUNX2 and BMP2 protein expression in aortic tissues. Additionally, Semaglutide also conferred protective effects in AGE-BSA stimulated mouse aortic smooth muscle cells (MOVAS). Autophagy, a lysosomal degradation pathway, is intimately involved in the pathological process of diabetic vascular calcification. During stimulation with AGEs-BSA, impaired lysosomal function and blocked autophagic flux were observed, as evidenced by increased protein levels of LC3-II and P62, alongside decreased expression of CTSD, CTSB, LAMP1 and LAMP2. These changes were accompanied by a decline in lysosomal pH, activity, and degradative capacity. Treatment with Semaglutide mitigated these abnormalities, restoring autophagic flux and lysosomal function, and consequently attenuating AGEs-BSA-induced calcification in MOVAS. Combined bioinformatics and Western blot analysis confirmed the significant downregulation of CPNE1 by Semaglutide in AGEs-BSA stimulated MOVAS. Copine-1 (CPNE1), a member of the copine protein family, is characterized as a calcium-dependent phospholipid-binding protein that primarily resides in the cytoplasm. These findings indicate that the attenuation of diabetic vascular calcification (DVC) by Semaglutide is associated with the inhibition of CPNE1-mediated autophagy, suggesting a potential novel therapeutic strategy for managing DVC.

Objective: We performed a meta-analysis of randomized controlled trials to assess the safety and efficacy of ticagrelor or other P2Y12 inhibitors in combination with oral anticoagulants as a part of DAPT/SAPT for the patients with atrial fibrillation (AF) and acute coronary disease (ACS) or undergoing percutaneous coronary intervention (PCI). Methods: We searched PubMed, Web of Science and ClinicalTrials.gov for randomized controlled trials (published from January 1, 1998, up to June 6, 2023; no language restrictions) comparing safety and efficacy of ticagrelor and DOACs or VKAs combination treatment arm with or without aspirin to other P2Y12 inhibitors treatment strategies. Main endpoints were clinically relevant bleeding as safety outcomes, all-cause mortality, and major adverse cardiovascular events (MACE) as efficacy outcomes. Results: Of 248 identified studies, 3 were eligible and were included in our analysis (N= 9463 participants). Ticagrelor and DOAC or VKA combination treatment with or without aspirin strategy was associated with an increased rate of bleeding compared with clopidogrel (odds ratio [OR] 1.39, 95% CI 1.15 to 1.67, I 2 =0%). MACE was similar between ticagrelor versus clopidogrel (OR 1.00, 95% CI 0.54 to 1.86, I 2 =68.1%) and between ticagrelor versus prasugrel (OR 0.86, 95% CI 0.28 to 2.65, I 2 =0%). Conclusion: The use of ticagrelor is associated with significantly higher rates of bleeding when compared with clopidogrel in patients with concomitant atrial fibrillation and coronary artery disease.

Background: Ischemic heart disease (IHD) is the leading cause of mortality and disability worldwide. This study aimed to investigate global trends in IHD mortality across 204 countries and territories over the past 30 years and explore the influence of age, period, birth, and cohort effects on mortality. Methods: IHD mortality data were retrieved from the Global Burden of Disease (GBD) 2019 study. Temporal trends in the number of deaths, all-age mortality rates, and age-standardized mortality rates were assessed across countries grouped by sociodemographic index (SDI) quintiles. To quantify changes over time, we fitted age–period–cohort (APC) models and derived overall annual percentage changes (net drift) and age-specific annual percentage changes (local drift). The APC model was then used to distinguish the independent effects of age, period, birth, and cohort on IHD mortality trends. Results: The annual global IHD deaths increased from 5.70 million (95% uncertainty interval (UI): 5.41–5.90) to 9.14 million between 1990 and 2019 (95% UI: 8.40–9.74). All-age mortality rates also rose significantly, with a notable shift in deaths toward older populations (≥70 years). The global net drift in IHD mortality declined by 1.10% annually (95% confidence interval (CI): –1.17% to –1.04%), with high-SDI countries experiencing the greatest decline (–2.84%, 95% CI: –3.05% to –2.64%). Age, period, and birth cohort effects manifested a general declining trend. The largest positive net drift was observed in the Philippines (3.60%, 95% CI: 3.33%–3.86%). Key global risk factors included hypertension, elevated low-density lipoprotein cholesterol, ambient particulate matter pollution, and smoking. However, low temperatures were the leading environmental risk factor in high-SDI countries. Conclusions: From 1990 to 2019, the global burden and temporal trends for IHD mortality varied substantially across SDI quintiles, sex, geographic regions, and countries. These disparities underscore the need for region-specific, risk-differentiated, and cost-effective interventions to prevent and manage IHD. Moreover, strengthening primary healthcare, improving health system responsiveness, and enhancing health promotion and prevention efforts are critical, especially in regions where IHD mortality remains stable or is increasing.

BACKGROUND: Vascular calcification (VC) is associated with diabetes, chronic kidney disease, and aging. VC is found to be a powerful and independent risk factor for cardiovascular mortality. Vascular smooth muscle cell (VSMC) ferroptosis, a form of cell death, is known to be involved in VC. However, whether VSMC ferroptosis is regulated by posttranslational modifications remains undefined. METHODS: We explored the potential role and mechanism of PARP1 (poly[ADP-ribose] polymerase 1)-mediated poly(ADP-ribosyl)ation (PARylation) in VSMC ferroptosis during VC. Mouse VSMCs were treated with β-glycerophosphate, and Parp1 ^flox/flox Tagln Cre ⁺ calcified mice were generated with AAV9-sh-POLG (DNA polymerase gamma) injected to establish in vitro and in vivo models, respectively. RNA-sequencing analysis was performed to determine the transcriptomic alterations in VSMCs overexpressing POLG and treated with β-glycerophosphate. RESULTS: Both PARP1 expression and PARylation levels were increased in β-glycerophosphate–induced VC, with PARP1 knockdown mitigating VC by improving mitochondrial function and inhibiting the subsequent VSMC ferroptosis. Mechanistically, POLG PARylation levels were increased in calcified VSMCs from PARP1 activation, triggering PARylation-dependent ubiquitination of POLG that resulted in POLG downregulation. This led to mitochondrial dysfunction and Adora2a (adenosine receptor A2A)/Rap1 (Ras-associated protein 1) signaling pathway activation to induce VSMC ferroptosis, which ultimately aggravated VC. CONCLUSIONS: Our study establishes the critical role of PARP1-mediated PARylation-dependent ubiquitination of POLG in VSMC ferroptosis-induced VC. These findings suggest that PARP1 inhibitors could potentially serve as novel therapeutic strategies for VC.

This study is the first to suggest the protective effect of activation of transcription factor EB (TFEB) against diabetic vascular calcification (VC), emphasizing that activation of TFEB alleviated diabetic VC by improving the autophagic flux and activating the Nuclear factor erythroid-2 related factor 2 (Nrf2) antioxidant system in vascular smooth muscle cells (VSMCs), and revealing that periostin (POSTN) partially abolished the protective effect of TFEB on diabetic VC by inhibiting the autophagic degradation of Kelch-like ECH-associated protein 1 (KEAP1).

To assess the link between persistent lipoprotein(a) [Lp(a)] exposure levels and clinical outcomes in patients with acute myocardial infarction (AMI). This longitudinal cohort study included 1131 AMI patients, categorizing persistent Lp(a) exposure based on measurements at admission and after 1 year. Patients were segmented into four groups using a 300 mg/L Lp(a) threshold: (1) persistent low Lp(a) (low_{on admission} - low_{at 1 year}); (2) fortified Lp(a) (low_{on admission} - high_{at 1 year}); (3) attenuated Lp(a) (high_{on admission} - low_{at 1 year}); and (4) persistent high Lp(a) (high_{on admission} - high_{at 1 year}). Multivariate Cox regression, subgroup analysis and sensitivity analysis assessed the association between Lp(a) trajectories and major adverse cardiovascular and cerebrovascular events (MACCE), cardiovascular death, non-fatal MI, non-fatal stroke, unplanned revascularization, and all-cause death. Over a median 50-month follow-up, 343 (35.70%) patients encountered MACCE, and 210 (18.70%) died, including 126 (11.20%) from cardiovascular causes. The group with persistent high Lp(a) faced increased risk of MACCE (HR_adjusted, 1.871; 95% CI: 1.474-2.374), non-fatal stroke (HR_adjusted, 1.647; 95% CI: 1.031-2.632), unplanned revascularization (HR_adjusted, 1.571; 95% CI: 1.008-2.449), and both all-cause (HR_adjusted, 1.546; 95% CI: 1.134-2.108) and cardiovascular death (HR_adjusted, 2.163; 95% CI: 1.405-3.331), compared to the persistent low Lp(a) group. In AMI patients, sustained high Lp(a) levels were significantly associated with increased risk of MACCE, non-fatal stroke, unplanned revascularization, and both all-cause and cardiovascular death.

Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.