Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis最新文献

{"title":"Association of Neutrophil-To-Lymphocyte Ratio and Atherogenic Index of Plasma With Angiographically Confirmed Coronary Artery Disease.","authors":"Xuexue Yang, Xiaofang Xiong, Dongsheng Li","doi":"10.1177/10760296261497036","DOIUrl":"https://doi.org/10.1177/10760296261497036","url":null,"abstract":"<p><p>BackgroundThe neutrophil-to-lymphocyte ratio (NLR) and atherogenic index of plasma (AIP) have been associated with coronary artery disease (CAD). We investigated their associations with angiographically confirmed CAD and lesion severity.MethodsThis retrospective study included 2,933 patients undergoing coronary angiography for suspected CAD at Wuhan Third Hospital. CAD was defined as ≥50% luminal stenosis in at least one major coronary artery or branch. Lesion severity was assessed using the Gensini score. Multivariable logistic regression and receiver operating characteristic analyses were performed.ResultsAmong 2,933 patients, 1,615 had CAD and 1,318 had no significant stenosis. NLR and AIP were higher in patients with CAD and increased across Gensini score categories (all P<0.05). After adjustment, AIP remained independently associated with CAD (OR=1.557, P=0.042), whereas NLR did not (OR=1.019, P=0.581). AIP alone showed limited discrimination (AUC=0.537). A multivariable model including age, blood pressure, fasting blood glucose, and AIP showed an AUC of 0.779. Adding AIP did not significantly improve AUC (DeLong P=0.153) or NRI (0.071, P=0.106), although IDI improvement was significant (0.002, P<0.05).ConclusionsIn patients undergoing coronary angiography for suspected CAD, NLR and AIP were associated with CAD and angiographic disease burden. AIP remained independently associated with CAD, whereas NLR did not. However, AIP showed limited discrimination and no clear incremental improvement beyond conventional variables. These findings do not support population screening or routine clinical implementation.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261497036"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Direct Oral Anticoagulants versus Aspirin in Patients with Non-Valvular Atrial Fibrillation and Intermediate Stroke Risk.","authors":"Susin Park, Nam Kyung Je","doi":"10.1177/10760296261416892","DOIUrl":"10.1177/10760296261416892","url":null,"abstract":"<p><p>AimsThis study compared the effectiveness and safety of direct oral anticoagulants (DOACs) versus aspirin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) and intermediate stroke risk, defined by a CHA₂DS₂-VASc score of 1 in men and 2 in women.MethodThis retrospective cohort study used Korean Health Insurance Review and Assessment Service claims data. Patients diagnosed with NVAF between January 1, 2017, and December 31, 2019, who initiated DOACs or aspirin, were included. Eligibility was restricted by CHA₂DS₂-VASc score, and patients were matched by age and sex to reduce confounding. The observation period extended until November 30, 2021. The primary outcomes were the incidence of ischemic stroke (effectiveness) and major bleeding events (safety).ResultsOf the 2234 patients included, 977 (43.7%) were treated with DOACs, and 1257 (56.3%) received aspirin. After matching, no statistically significant differences were observed between the DOAC and aspirin groups in ischemic stroke incidence (1.46 vs 0.92 per 100 person-years, <i>P</i> = .060) or major bleeding events (2.26 vs 2.10 per 100 person-years, <i>P</i> = .100). Notably, rheumatic disease was associated with an increased risk of ischemic stroke, while liver disease was linked to a higher risk of major bleeding.ConclusionIn NVAF patients with intermediate stroke risk, no statistically significant differences were observed in ischemic stroke or major bleeding between DOACs and aspirin. These results should not be interpreted as therapeutic equivalence but highlight the need for further real-world research, particularly in Asian populations, to inform optimal antithrombotic strategies in this subgroup.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261416892"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Exosomal MicroRNAs as Potential Biomarkers for Pulmonary Embolism.","authors":"Chongyu Zhang, Bulent Kantarcioglu, Prakasha Kempaiah, Srdjan Nikolovski, Fakiha Siddiqui, Ahmed Kouta, Fabio Lievano, Thao Doan, Simon Kaja, Amir Darki, Jawed Fareed, W Keith Jones","doi":"10.1177/10760296251407689","DOIUrl":"10.1177/10760296251407689","url":null,"abstract":"<p><p>Pulmonary embolism (PE) is difficult to diagnose due to nonspecific symptomatology and lack of accurate diagnostic tools. PE can be categorized into low-risk, submassive, and massive based on severity. Changes in several plasma and serum microRNAs (miRNA) are associated with PE, but most lack appropriate specificity for diagnostic utility. Given the emerging role of small extracellular vesicles (sEVs) in PE pathogenesis, we hypothesized that the microRNAs (miRs) circulating within these sEVs can be sampled to gain new information for biomarker studies and disease mechanisms. To address current technical limitations, we developed a novel high-yield size-exclusion chromatography (SEC) method for sEV isolation from small clinical plasma samples, and employed a non-biased method, RNA-Seq, to gain new information for RNA markers that have not been previously studied in the disease. Our goal was to establish the feasibility of the approach in a pilot study with pooled samples from a stratified (AHA criteria) patient population. We present information from sEV characterization studies of individual patient samples, and RNA-Seq data from the pools. PE patients had larger sEVs than healthy subjects. Small RNA sequencing of the sEV samples revealed differential miRNA expression patterns that correlated with PE severity and were predicted to be involved in PE pathology-related processes. Our data offer a first step toward identifying miRNA targets that may have utility in a miRNA biomarker panel for PE diagnosis, prediction of severity, treatment responses and adverse outcomes. This strategy can be extended to the detection of adverse effects and drug-drug interactions as well.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296251407689"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13208706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Value of miR-1225-5p in Acute Coronary Syndrome and its Mechanism in ox-LDL Induced Human Coronary Artery Endothelial Cells Injury.","authors":"Han Ju, Pengxian Si, Sheng Li, Dengkui Yang","doi":"10.1177/10760296251414428","DOIUrl":"10.1177/10760296251414428","url":null,"abstract":"<p><p>BackgroundAcute coronary syndrome (ACS), a life-threatening cardiovascular emergency, faces challenges in early diagnosis and risk stratification. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases.ObjectivesTo investigate the diagnostic/predictive significance of miR-1225-5p in ACS and its mechanism of regulating human coronary artery endothelial cells (HCAECs) injury induced by ox-LDL via targeting FAS.MethodsmiR-1225-5p levels in serum were determined by RT-qPCR in 99 ACS patients and controls, with correlation analysis to clinical indicators. HCAECs were used to assess viability, apoptosis, and inflammation/oxidative stress (IL-6, TNF-α, MDA, SOD) via CCK-8, flow cytometry, and ELISA. Target binding between FAS and miR-1225-5p was validated by dual-luciferase reporter and RIP assays, with functional validation experiments.ResultsmiR-1225-5p was significantly downregulated in ACS (<i>P</i> < 0.001), with subtype-specific patterns (UA > NSTEMI > STEMI). ROC analysis showed high diagnostic accuracy (AUC = 0.885 for ACS; 0.790-0.964 for subtypes). miR-1225-5p (HR = 5.409, 95% CI = 1.281-22.837) and Gensini score (HR = 3.524, 95% CI = 1.066-11.646) acted as a predictive factor in ACS, and downregulated miR-1225-5p is linked to MACEs in ACS patients. Overexpression of miR-1225-5p alleviated ox-LDL-induced HCAECs injury (enhanced viability, suppressed apoptosis, reduced inflammation/oxidative stress). FAS acted as a specific target of miR-1225-5p and is negatively associated with miR-1225-5p (r = -0.721). Overexpression of FAS reversed miR-1225-5p-mediated protective effects on HCAECs.ConclusionmiR-1225-5p is a potential diagnostic indicator for ACS and alleviates HCAECs injury by targeting FAS.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296251414428"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rotational Thromboelastometry and Bleeding Risk in Child-Pugh C Cirrhosis: Methodological Considerations.","authors":"Güney Sarıoğlu","doi":"10.1177/10760296261486179","DOIUrl":"10.1177/10760296261486179","url":null,"abstract":"","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261486179"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing Beats and Bleeding: The Evolving Landscape of Atrial Fibrillation and Anticoagulation in the Past Two Decades.","authors":"Boshui Huang, Chenhao Ouyang, Kaiyan Fan, Yifan Wu, Ran Mo, Wenli Gu, Jing Zhang, Jun Zhang, Xiang Gu, Wengen Zhu, Yuling Zhang, Jingfeng Wang, Yangxin Chen, Wenting Wang, Xiao Liu","doi":"10.1177/10760296261468526","DOIUrl":"10.1177/10760296261468526","url":null,"abstract":"<p><p>BackgroundAnticoagulation has been the cornerstone for stroke prevention in patients with atrial fibrillation (AF). This study aims to describe the research trends and research hotspots in anticoagulation and AF.MethodsPublications on AF and anticoagulation were retrieved from the Web of Science Core Collection from 2004 to 2024 for bibliometric analyses.ResultsA total of 12,551 articles were retrieved. The number of publications increased each year, reaching its peak in 2021. The United States has the largest number of published articles (country appearances, 18,181), followed by Italy (6525) and Japan (6,235). The most productive institutions were Harvard University (658), McMaster University (570), and the University of Birmingham (550). LIP GYH was the most prolific author, with 707 articles published. 'Circulation' has the highest H-index (77), followed by the 'Thrombosis and Hemostasis' (73), 'Journal of the American College of Cardiology' (72). The keyword analysis revealed that the research focused on warfarin, stroke, dabigatran, direct oral anticoagulants, rivaroxaban, antithrombotic therapy, prevention, safety, apixaban, and venous thromboembolism.ConclusionsResearch in AF and anticoagulation has expanded rapidly. Coagulation contact phase (such as coagulation factor XI and XII) inhibitors have emerged as a promising future therapeutic target, and there is a critical need for global collaboration to validate these strategies across diverse populations.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261468526"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explore the Causal Effect of SGLT2 Inhibition on Venous Thromboembolism Events: A Drug-Target Mendelian Randomization Study With Pharmacovigilance Analysis.","authors":"Jing Liu, Zipei Ma, Piaoran Liu, Tiezhu Yao, Jing He, Tenghui Wang, Mengjia Li, Sihan Liu, Jingtao Ma, Zhenli Li","doi":"10.1177/10760296261457239","DOIUrl":"10.1177/10760296261457239","url":null,"abstract":"<p><p>BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antidiabetic agents with established cardiorenal benefits, yet their genetic causal association with venous thromboembolism (VTE) remains uncertain.MethodsWe employed a multifaceted approach to investigate the causal relationship between SGLT2 inhibition and VTE, as well as deep vein thrombosis (DVT) and pulmonary embolism (PE). Drug-target Mendelian randomization (MR) and summary-data-based MR (SMR) analyses were conducted using genetic variants proxying SGLT2 inhibition, derived from <i>SLC5A2</i> expression quantitative trait loci and glycemic traits. Positive control analyses confirmed validity using type 2 diabetes outcomes. Meta-analyses were performed across multiple independent genome-wide association study datasets. Complementary pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System (FAERS) to assess disproportionality of SGLT2 inhibitor-related VTE reports.ResultsGenetically proxied SGLT2 inhibition was significantly associated with reduced risk of type 2 diabetes (P < 0.05), validating its robustness. Most MR analyses showed no consistent causal association with VTE, DVT, or PE across datasets, and meta-analyses yielded non-significant pooled estimates (all P > 0.05). SMR analyses revealed no association between <i>SLC5A2</i> expression and VTE-related outcomes (all P_SMR > 0.05). FAERS disproportionality analysis also identified no safety signals for PE (reporting odds ratio [ROR] = 0.51; 95% CI: 0.42-0.64) or DVT (ROR = 0.54; 95% CI: 0.45-0.64).ConclusionsThis integrative study provides consistent evidence that SGLT2 inhibition is not causally associated with VTE, DVT, or PE, supporting its thrombotic safety. However, generalizability to non-European populations requires future validation in diverse cohorts.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261457239"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Causal Effects of Inflammation and Coagulation-Related Biomarkers on Sepsis-Related Complications: A Mendelian Randomization Study.","authors":"Qi Yao, Yiran Yao, Zhe Liao, Jing Wang, Mengmeng Yu","doi":"10.1177/10760296261438237","DOIUrl":"10.1177/10760296261438237","url":null,"abstract":"<p><p>BackgroundSepsis and its complications pose a major global health burden. Mendelian randomization (MR) provides a genetic approach to assess causality.MethodsWe conducted a two-sample Mendelian randomization (MR) study using data from large-scale genome-wide association studies (GWAS). This study aimed to assess the causal effects of six key biomarkers (D-dimer, Galectin-3, activated protein C, tumor necrosis factor receptor 2, interleukin-6 receptor subunit alpha, and thrombomodulin) on six sepsis-related complications, including acute respiratory distress syndrome (ARDS) and acute renal failure. The primary analysis utilized the inverse-variance weighted (IVW) method, with comprehensive sensitivity analyses to assess for heterogeneity and pleiotropy. A False Discovery Rate (FDR) was applied to correct for multiple testing.ResultsThe primary IVW analysis suggested several potential causal associations. Genetically predicted D-dimer was associated with a lower risk of ARDS (OR = 0.63, <i>P</i> = 0.025), IL-6Rα with a reduced risk of acute renal failure (OR = 0.85, <i>P</i> = 0.035), and Galectin-3 with a lower risk of streptococcal septicaemia (OR = 0.95, <i>P</i> = 0.039). Reverse MR analysis suggested that genetic liability to sepsis (critical care) was associated with lower D-dimer levels. However, after FDR correction, none of these associations remained statistically significant. Sensitivity analyses did not indicate the presence of significant horizontal pleiotropy.ConclusionThis study did not find robust genetic evidence to support a causal relationship between the six selected biomarkers and the risk of sepsis-related complications after correction for multiple testing. The suggestive associations observed prior to correction warrant further investigation.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261438237"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dilemma of Providing Advanced Hemophilia Treatments in Developing Countries - For Whom, by Whom and Where?","authors":"Kaan Kavaklı, Canan Albayrak, Bulent Antmen, Selin Aytac, Can Balkan, Zuhre Kaya, Alphan Kupesiz, Vahap Okan, Mehmet Sonmez, Fahri Sahin, Ekrem Unal, Bulent Zulfikar","doi":"10.1177/10760296261459710","DOIUrl":"10.1177/10760296261459710","url":null,"abstract":"<p><p>Hemophilia, a congenital deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B), leads to recurrent bleeding episodes that may cause progressive joint damage and long-term disability. Traditional management relies on intravenous factor replacement therapy; however, limited half-life, immunogenicity, venous access challenges, and the burden of frequent infusions have prompted the development of extended half-life (EHL) factor products. Although EHL therapies represent an important advancement, they only partially reduce treatment burden and do not fully meet expectations for improved convenience and sustained bleed protection. Recent innovations are reshaping the therapeutic landscape. Nonfactor subcutaneous therapies such as anti-TFPI molecules, antithrombin reducing agents, and anti-protein C agents offer simplified administration with the potential for improved adherence. Gene therapy provides the prospect of a long-term therapeutic effect in selected patients. In Türkiye, hemophilia care remains largely factor-based; however, clinical trial participation and recent regulatory approvals for selected novel therapies have begun to expand real-world experience with these emerging treatment options. As global practice shifts toward individualized, less invasive treatment approaches, expanding availability of novel therapies and optimizing patient-specific treatment strategies will be essential. This review examines current and evolving treatment options, key challenges, and future opportunities shaping the trajectory of hemophilia management.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261459710"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13260973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HbA1c as an Independent Predictor of Peripheral Artery Disease: Nonlinear Threshold and Causal Evidence from NHANES and Mendelian Randomization.","authors":"Xixi Guo, Jianke Wang, Qiang Guo, Kai Zheng, Bin Ni, Xueqiang Fan, Qiangqiang Nie","doi":"10.1177/10760296261437047","DOIUrl":"10.1177/10760296261437047","url":null,"abstract":"<p><p>BackgroundPeripheral artery disease (PAD) is a major contributor to cardiovascular morbidity and mortality, yet reliable biomarkers for early detection remain limited. Glycated hemoglobin (HbA1c) reflects long-term glycemia, but its relationship with PAD in the general population remains incompletely understood.MethodsWe analyzed 6284 adults aged ≥40 years from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). PAD was defined as an ankle-brachial index ≤0.90. Weighted logistic regression, restricted cubic spline, and threshold models evaluated associations between HbA1c and PAD. To further examine causality, a two-sample Mendelian randomization (MR) using genome-wide association data on HbA1c (n = 389,889) and PAD (7098 cases, 206541 controls) was conducted.ResultsIn NHANES, each 1% increment in HbA1c was linked to a higher likelihood of PAD (fully adjusted OR 1.18, 95% CI 1.04-1.34). Participants in the highest HbA1c tertile had more than a twofold greater risk compared with those in the lowest (OR 2.30, 95% CI 1.68-3.15). Restricted cubic spline analysis revealed a nonlinear relationship with a threshold at 6.11%, below which PAD risk rose steeply. In MR analysis, genetically predicted HbA1c was positively associated with PAD risk, showing that genetically predicted HbA1c was positively associated with PAD (IVW OR 1.23, 95% CI 1.10-1.37, p = 0.0002), with consistent results across sensitivity analyses.ConclusionElevated HbA1c is independently and causally linked to PAD risk, with a nonlinear dose-response pattern. These findings support HbA1c as a potential tool for identifying individuals at higher PAD risk.</p>","PeriodicalId":520590,"journal":{"name":"Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis","volume":"32 ","pages":"10760296261437047"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13080148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}