Background: This study investigated whether expanding waist circumference (WC) is causally associated with an elevated risk of coronary heart disease (CHD), using a two‐sample Mendelian randomization (MR) study through integrating summarized data from genome‐wide association study. Methods: The data included in this analysis were mainly from the Genetic Investigation of ANthropometric Traits (GIANT), Consortium and Coronary Artery Disease Genome wide Replication, and Meta‐analysis plus the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) Consortium. Three statistical approaches, inverse‐variance weighted (IVW), weighted median, and MR‐Egger regression method were conducted to assess the casual relationship. The exposure was WC, measured by 46 single‐nucleotide polymorphisms from GIANT and the outcome was the risk of CHD. Then, we used the genetic data from Neale Lab and TAG to infer whether WC causally affected the established risk factors of CHD. Results: The IVW method presented that genetically predicted WC was positively casually associated with CHD (odds ratio [OR]: 1.57, 95% CI = 1.33–1.84; p = 4.81e‐08), which was consistent with the result of weighted median and MR‐Egger regression. MR‐Egger regression indicated that there was no directional horizontal pleiotropy to violate the MR assumption. Additionally, expanded WC was also associated with higher risk of hypertension and diabetes, higher cholesterol, more smoking intensity, and decreased frequency of physical activity. Conclusion: Our analysis provided strong evidence to indicate a causal relationship between WC and increased risk of CHD.

Atheroclerosis refers to a chronic inflammatory disease featured by the accumulation of fibrofatty lesions in the intima of arteries. Cardiovasular events associated with atherosclerosis remain the major causes of mortality worldwide. Recent studies have indicated that ferroptosis, a novel programmed cell death, might participate in the process of atherosclerosis. However, the ferroptosis landscape is still not clear. In this study, 59 genes associated with ferroptosis were ultimately identified in atherosclerosis in the intima. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for functional annotation. Through the construction of protein–protein interaction (PPI) network, five hub genes (TP53, MAPK1, STAT3, HMOX1, and PTGS2) were then validated histologically. The competing endogenous RNA (ceRNA) network of hub genes was ultimately constructed to explore the regulatory mechanism between lncRNAs, miRNAs, and hub genes. The findings provide more insights into the ferroptosis landscape and, potentially, the therapeutic targets of atherosclerosis.

Peripheral artery disease (PAD) is often asymptomatic but increases the risk of developing cardiovascular events. Due to the uncertainties regarding the quality of related guidelines and a lack of clear-cut evidence, we performed a systematic review and critical appraisal of these guidelines to evaluate their consistency of the recommendations in asymptomatic PAD population. Guidelines in English between January 1st, 2000 to December 31th, 2017 were screened in databases including Medline via PubMed, EMBASE, the G-I-N International Guideline Library, the National Guidelines Clearinghouse, the Canadian Medication Association Infobase and the National Library for Health. Those guidelines containing recommendations on screening and treatment for asymptomatic PAD were included, and three reviewers evaluated the quality of the guidelines using Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Related recommendations were then fully extracted and compared by two reviewers. Fourteen guidelines were included finally and the AGREE scores ranged from 39 to 73%. Most of included guidelines scored low in Rigor of development and Editorial independence, and only two guidelines (ACCF/AHA, AHA/ACC) reached the standard on Conflict of Interest from Institute of Medicine (IOM). Eight guidelines recommended screening at different strength while the others found insufficient evidence or were against screening. Conflicting recommendations on treatment were found in the target value of the lipid lowering and antiplatelet therapy. The treatment policies in three guidelines (BWG, CEVF, ESC) appeared more aggressive, but they had low transparency between guideline developer and industry or did not reach the standard of IOM. Current guidelines on asymptomatic PAD varied in the methodological quality and fell short of the standard in the rigor of development and editorial independence. Conflicting recommendations were found both on the screening and treatment. More effort is needed to provide clear-cut evidences with high quality and transparency among guideline developer and industry.

The singular forms of programmed cell death (PCD), including pyroptosis, apoptosis, and necroptosis, are inadequate for comprehensively elucidating the complex pathological mechanisms underlying ischemic diseases. PANoptosis is a unique lytic, innate immune, and inflammatory cell death pathway, initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. In diseases like cerebral ischemia, retinal ischemia, myocardial ischemia, renal ischemia, and spinal cord ischemia, targeting key regulatory factors of PANoptosis can help mitigate tissue damage. Therefore, the therapeutic potential of PANoptosis in ischemic diseases—from molecular mechanisms to clinical applications—merits further investigation. However, effectively regulating PANoptosis to achieve therapeutic outcomes remains a critical scientific challenge that must be addressed. This review focuses on the molecular mechanisms of PANoptosis in ischemic diseases and its potential therapeutic implications, aiming to provide new insights and a theoretical foundation for precision treatment in these conditions.

Lower-limb ischemia–reperfusion injury (LL-IRI) is a frequent and serious complication following reperfusion therapy for lower-limb arterial occlusion. It can be caused by trauma, arterial stenosis, thrombotic occlusion, and atherosclerosis. As a prevalent peripheral vascular disease, LL-IRI results in local tissue damage and triggers systemic inflammatory responses that can lead to multiple-organ dysfunction syndrome, as well as multiorgan failure and death in severe cases. Despite its clinical significance, the mechanisms underlying IRI remain poorly understood, and no specific targeted drugs or effective emergency interventions are currently available. Therefore, this review provides a comprehensive analysis of the domestic and international literature published over the past decade regarding the disease definition, pathogenesis, and therapeutic advances in LL-IRI. It summarizes current pharmacological and non-pharmacological interventions, including antioxidant stress management, anti-inflammatory approaches, and oxidative stress reduction strategies. This review aims to advance the exploration of LL-IRI pathogenesis and proposes novel therapeutic perspectives for innovative drug development.