{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:36:48Z","timestamp":1770813408434,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Helicobacter pylori (\n                      <jats:italic>H.pylori<\/jats:italic>\n                      ) has been implicated in peripheral atherosclerosis (PA); however, its predictive value for PA risk in large population-based cohorts remains insufficiently characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study aimed to evaluate assess the predictive contribution of\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection to PA risk, in combination with traditional clinical factors, using interpretable machine learning (ML) models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective cohort of 5,862 individuals undergoing routine health check-ups was analyzed. Demographic data, laboratory indices, and lower-extremity vascular ultrasound findings were collected to determine PA status and\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection. Key risk factors were identified through univariate and multivariate logistic regressions. Subgroup and restricted cubic spline (RCS) analyses were applied to evaluate effect modification and nonlinear associations. Fourteen ML algorithms were developed and evaluated using the area-under-curve (AUC), sensitivity, accuracy, specificity, positive-predictive-value (PPV), negative-predictive-value (NPV), F1-score, Youden\u2019s index, and calibration. Models were subsequently retrained using regression-identified variables to assess stability. SHapley Additive exPlanations (SHAP) analysis was employed to interpret feature importance from across models. Longitudinal and mediation analyses were conducted to explore temporal relationships and the potential mediating role of the triglyceride-glucose (TyG) index.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection was independently associated with PA (odds ratio (OR)=5.27, 95%CI=4.27-6.54,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;0.001), alongside male (OR = 5.88, 95%CI=4.22-8.29,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;0.001), smoking (OR = 2.11, 95%CI=1.67-2.67,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;0.001), and elevated low-density lipoprotein levels (OR = 2.10, 95%CI=1.47-3.04,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;0.001). Subgroup and RCS analyses demonstrated consistent and nonlinear associations with PA outcomes. ML models using all variables achieved excellent predictive performance, including AUC = 0.993, accuracy=0.981, sensitivity=0.954, specificity=0.990, PPV = 0.966, NPV = 0.986, F1-score=0.960 and Youden\u2019s index=0.944. After restricting predictors to regression-identified variables, the CatBoost model maintained acceptable discrimination, with an AUC = 0.754, accuracy=0.785, sensitivity=0.342, specificity=0.925, PPV = 0.621, NPV = 0.823, F1-score =0.441 and Youden\u2019s index=0.279. SHAP analysis consistently ranked\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection as the top predictor. Longitudinal analysis revealed a higher proportion of persistent\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection in emerging PA cases. Mediation analysis indicated a negligible indirect effect of the TyG index (1.11%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.124).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>H.pylori<\/jats:italic>\n                      infection is independently associated with PA and represents a critical contributor to PA risk stratification. The integration of epidemiological analysis with interpretable ML provides a robust framework for identifying high-risk individuals and supports the potential value of incorporating infectious markers into vascular risk assessment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1693262","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:37:07Z","timestamp":1770795427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interpretable machine learning analysis for relationships between Helicobacter pylori infection and peripheral atherosclerosis: a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Chenlu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Affiliated Yueqing Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingshi","family":"Lin","sequence":"additional","affiliation":[{"name":"Interventional therapy Department, Affiliated Yueqing Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liaoliao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Yueqing Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.3390\/s25051410","article-title":"A review of machine learning and deep learning methods for person detection, tracking and identification, and face recognition with applications","volume":"25","author":"Amirgaliyev","year":"2025","journal-title":"Sensors (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13098-021-00765-x","article-title":"Association of Helicobacter pylori infection with the risk of metabolic syndrome and insulin resistance: an updated systematic review and meta-analysis","volume":"13","author":"Azami","year":"2021","journal-title":"Diabetol. Metab. Syndr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-62703-748-8_7","article-title":"Introduction to machine learning","volume":"1107","author":"Bastanlar","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1470993","article-title":"Serum high sensitive C-reactive protein level and its correlation with lipid profile among dyspeptic patients with or without Helicobacter pylori infection in East Gojjam zone, Ethiopia","volume":"11","author":"Baye","year":"2024","journal-title":"Front. Cardiovasc. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3889\/oamjms.2020.3199","article-title":"Interleukin-6, tumor necrosis factor-\u03b1, and high-sensitivity C-reactive protein in diabetic patients with helicobacter pylori in Kosovo","volume":"8","author":"Begolli-Stavileci","year":"2020","journal-title":"Open Access Macedonian J. Med. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s13167-019-00196-9","article-title":"Evaluation of machine learning methodology for the prediction of healthcare resource utilization and healthcare costs in patients with critical limb ischemia-is preventive and personalized approach on the horizon","volume":"11","author":"Berger","year":"2020","journal-title":"EPMA J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.3390\/biomedicines13061291","article-title":"Atherosclerosis and insulin resistance: is there a link between them","volume":"13","author":"Brie","year":"2025","journal-title":"Biomedicines."},{"key":"B8","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jss.2020.02.012","article-title":"Deep learning-based risk model for best management of closed groin incisions after vascular surgery","volume":"254","author":"Chang","year":"2020","journal-title":"J. Surg. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1093\/cvr\/cvad106","article-title":"A machine learning based approach to identify carotid subclinical atherosclerosis endotypes","volume":"119","author":"Chen","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3325\/cmj.2016.57.141","article-title":"Helicobacter pylori in sedentary men is linked to higher heart rate, sympathetic activity, and insulin resistance but not inflammation or oxidative stress","volume":"57","author":"Cherkas","year":"2016","journal-title":"Croat Med. J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1136\/gut.32.12.1473","article-title":"Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis","volume":"32","author":"Crabtree","year":"1991","journal-title":"Gut."},{"key":"B12","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2174\/157016112799959305","article-title":"Insulin- and growth factor-resistance impairs vascular regeneration in diabetes mellitus","volume":"10","author":"Cubbon","year":"2012","journal-title":"Curr. Vasc. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1080\/0954898X.2024.2331506","article-title":"Comparative performance analysis of Boruta, SHAP, and Borutashap for disease diagnosis: A study with multiple machine learning algorithms","volume":"36","author":"Ejiyi","year":"2025","journal-title":"Network."},{"key":"B14","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jacl.2020.11.005","article-title":"Impaired cholesterol efflux capacity in patients with Helicobacter pylori infection and its relation with inflammation","volume":"15","author":"Fallah","year":"2021","journal-title":"J. Clin. Lipidol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"429","DOI":"10.3238\/arztebl.2018.0429","article-title":"Helicobacter pylori infection","volume":"115","author":"Fischbach","year":"2018","journal-title":"Dtsch Arztebl Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1210\/jc.2010-0288","article-title":"The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp","volume":"95","author":"Guerrero-Romero","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1016\/j.amjmed.2008.10.014","article-title":"Diagnosis of atherosclerosis by imaging","volume":"122","author":"Iba\u00f1ez","year":"2009","journal-title":"Am. J. Med."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.925923","article-title":"Mechanisms of oxidized LDL-mediated endothelial dysfunction and its consequences for the development of atherosclerosis","volume":"9","author":"Jiang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1001\/archinte.165.16.1896","article-title":"Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study","volume":"165","author":"Kennedy","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2471\/BLT.19.237198","article-title":"Artificial intelligence and the ongoing need for empathy, compassion and trust in healthcare","volume":"98","author":"Kerasidou","year":"2020","journal-title":"Bull. World Health Organ."},{"key":"B21","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13098-018-0376-8","article-title":"Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance","volume":"10","author":"Khan","year":"2018","journal-title":"Diabetol. Metab. Syndr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.3390\/jcm9061856","article-title":"Chronic gastritis is associated with a decreased high-density lipid level: histological features of gastritis based on the updated sydney system","volume":"9","author":"Kim","year":"2020","journal-title":"J. Clin. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1177\/1358863X19894055","article-title":"Statin therapy for reduction of cardiovascular and limb-related events in critical limb ischemia: A systematic review and meta-analysis","volume":"25","author":"Kokkinidis","year":"2020","journal-title":"Vasc. Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1320335","article-title":"Predictive model and risk analysis for peripheral vascular disease in type 2 diabetes mellitus patients using machine learning and shapley additive explanation","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"B25","article-title":"A unified approach to interpreting model predictions","volume":"30","author":"Lundberg","year":"2017","journal-title":"Adv. Neural Inf. Process. Syst."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1016\/j.jacc.2019.10.009","article-title":"The global burden of cardiovascular diseases and risk factors: 2020 and beyond","volume":"74","author":"Mensah","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1196\/annals.1366.032","article-title":"Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections","volume":"1088","author":"Moutsopoulos","year":"2006","journal-title":"Ann. N Y Acad. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"011505","DOI":"10.1063\/5.0028986","article-title":"Application of machine learning in understanding atherosclerosis: Emerging insights","volume":"5","author":"Munger","year":"2021","journal-title":"APL Bioeng."},{"key":"B29","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/hel.12182","article-title":"Effects of Helicobacter pylori infection and its eradication on lipid profiles and cardiovascular diseases","volume":"20","author":"Nam","year":"2015","journal-title":"Helicobacter."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1016\/j.jacc.2018.08.002","article-title":"Pathology of peripheral artery disease in patients with critical limb ischemia","volume":"72","author":"Narula","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/j.jacc.2005.01.019","article-title":"Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects","volume":"45","author":"Oshima","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.ahj.2005.06.041","article-title":"Virulent strains of Helicobacter pylori and vascular diseases: a meta-analysis","volume":"151","author":"Pasceri","year":"2006","journal-title":"Am. Heart J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2174\/187153012803832602","article-title":"Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst","volume":"12","author":"Peluso","year":"2012","journal-title":"Endocr. Metab. Immune Disord. Drug Targets."},{"key":"B34","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s43044-021-00185-2","article-title":"Association of Helicobacter pylori infection with coronary artery disease: is it an independent risk factor","volume":"73","author":"Riad","year":"2021","journal-title":"Egypt Heart J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1160\/TH11-06-0392","article-title":"Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis","volume":"106","author":"Rosenfeld","year":"2011","journal-title":"Thromb. Haemost."},{"key":"B36","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/s10156-008-0613-4","article-title":"Chronic Helicobacter pylori infection is associated with peripheral arterial disease","volume":"14","author":"Sawayama","year":"2008","journal-title":"J. Infect. Chemother."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12865","article-title":"Helicobacter pylori infection and the progression of atherosclerosis: A systematic review and meta-analysis","volume":"27","author":"Shi","year":"2022","journal-title":"Helicobacter."},{"key":"B38","first-page":"6785","article-title":"Attend and predict: understanding gene regulation by selective attention on chromatin","volume":"30","author":"Singh","year":"2017","journal-title":"Adv. Neural Inf Process Syst."},{"key":"B39","doi-asserted-by":"publisher","first-page":"010601","DOI":"10.7189\/jogh.09.010601","article-title":"National and subnational estimation of the prevalence of peripheral artery disease (PAD) in China: a systematic review and meta-analysis","volume":"9","author":"Song","year":"2019","journal-title":"J. Glob Health"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e1020","DOI":"10.1016\/S2214-109X(19)30255-4","article-title":"Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis","volume":"7","author":"Song","year":"2019","journal-title":"Lancet Glob Health"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e12967","DOI":"10.1111\/hel.12967","article-title":"Helicobacter pylori infection and risk of cardiovascular disease","volume":"28","author":"Sun","year":"2023","journal-title":"Helicobacter."},{"key":"B42","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2147\/IJGM.S345649","article-title":"Evaluation of lipid profile and inflammatory marker in patients with gastric Helicobacter pylori infection, Ethiopia","volume":"12","author":"Temesgen","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart disease and stroke statistics-2022 update: A report from the american heart association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12761","article-title":"A meta-analysis of the association between Helicobacter pylori infection and risk of atherosclerotic cardiovascular disease","volume":"25","author":"Wang","year":"2020","journal-title":"Helicobacter"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1007\/s10096-017-3054-0","article-title":"Helicobacter pylori infection and atherosclerosis: is there a causal relationship","volume":"36","author":"Xu","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/hel.13030","article-title":"Interactions between Helicobacter pylori infection and host metabolic homeostasis: A comprehensive review","volume":"28","author":"Ye","year":"2023","journal-title":"Helicobacter."},{"key":"B47","doi-asserted-by":"publisher","first-page":"6799","DOI":"10.1038\/s41598-025-90919-y","article-title":"Machine learning for early diagnosis of Kawasaki disease in acute febrile children: retrospective cross-sectional study in China","volume":"15","author":"Zheng","year":"2025","journal-title":"Sci. Rep."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e35586","article-title":"Data-driven rapid detection of Helicobacter pylori infection through machine learning with limited laboratory parameters in Chinese primary clinics","volume":"10","author":"Zhu","year":"2024","journal-title":"Heliyon."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1693262\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:37:08Z","timestamp":1770795428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1693262\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":48,"alternative-id":["10.3389\/fcimb.2026.1693262"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1693262","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"article-number":"1693262"}}