{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:29:00Z","timestamp":1793647740322,"version":"4.5.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"42","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Endothelial dysfunction is prevalent in type 2 diabetes mellitus (T2DM) with coronary heart disease (CHD), increasing cardiovascular risk. The Endothelial Activation and Stress Index (EASIX) is a novel composite biomarker, yet its prognostic value in this comorbid population remains unclear. In this prospective cohort study, we analyzed 909 participants with T2DM and CHD from National Health and Nutrition Examination Survey 1999 to 2010, followed until 2019. EASIX was calculated using lactate dehydrogenase, creatinine, and platelet count. Multivariable Cox regression and Fine-Gray competing-risk models assessed associations between EASIX and all-cause and cardiovascular mortality, respectively. Time-dependent\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      -statistic, net reclassification improvement, and integrated discrimination improvement evaluated the incremental prognostic value of EASIX beyond established risk factors. During a median follow-up of 111 months, 617 all-cause and 251 cardiovascular deaths occurred. Higher EASIX levels were significantly associated with increased mortality risks. In fully adjusted models, the highest quartile had a hazard ratio of 1.93 (95% confidence interval\u2005=\u20051.48\u20132.50) for all-cause mortality and a subdistribution hazard ratio of 1.56 (95% confidence interval\u2005=\u20051.05\u20132.33) for cardiovascular mortality compared with the lowest quartile. Restricted cubic spline analysis revealed a significant nonlinear positive relationship. Adding EASIX to a base model (age, HbA1c, and estimated glomerular filtration rate) significantly improved the\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      -statistic, net reclassification improvement, and integrated discrimination improvement for both outcomes (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005&lt;\u2005.001). Elevated EASIX levels are independently associated with higher all-cause and cardiovascular mortality in patients with T2DM and CHD. In this population, its inclusion in risk assessment protocols enhances the predictive value for long-term clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/md.0000000000051166","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:00:52Z","timestamp":1792173652000},"page":"e51166","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Association of Endothelial Activation and Stress Index (EASIX) with long-term mortality in type 2 diabetes patients with coronary heart disease"],"prefix":"10.1097","volume":"105","author":[{"given":"Cancan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2013-030X","authenticated-orcid":false,"given":"Kuanlu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20261102","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12933-023-01875-8","article-title":"Intensified glycemic control by HbA1c for patients with coronary heart disease and type 2 diabetes: a review of findings and conclusions.","volume":"22","author":"Chen","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"R2-20261102","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.tcm.2021.04.002","article-title":"Coronary heart disease risk: low-density lipoprotein and beyond.","volume":"32","author":"Shaya","year":"2022","journal-title":"Trends Cardiovasc Med"},{"key":"R3-20261102","doi-asserted-by":"crossref","first-page":"6118","DOI":"10.3390\/ijms22116118","article-title":"The emerging roles of chromogranins and derived polypeptides in atherosclerosis, diabetes, and coronary heart disease.","volume":"22","author":"Watanabe","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R4-20261102","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/j.jcin.2023.08.035","article-title":"Another piece in the diabetes and multivessel coronary disease puzzle.","volume":"16","author":"Farkouh","year":"2023","journal-title":"JACC Cardiovasc Interv"},{"key":"R5-20261102","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00125-020-05319-w","article-title":"Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.","volume":"64","author":"Nanayakkara","year":"2021","journal-title":"Diabetologia"},{"key":"R6-20261102","doi-asserted-by":"crossref","first-page":"107832","DOI":"10.1016\/j.pharmthera.2021.107832","article-title":"Endothelial function and dysfunction: impact of sodium-glucose cotransporter 2 inhibitors.","volume":"224","author":"Ugusman","year":"2021","journal-title":"Pharmacol Ther"},{"key":"R7-20261102","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1124\/pharmrev.120.000096","article-title":"Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies.","volume":"73","author":"Xu","year":"2021","journal-title":"Pharmacol Rev"},{"key":"R8-20261102","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.tem.2024.11.004","article-title":"Intracellular endothelial cell metabolism in vascular function and dysfunction.","volume":"36","author":"Citrin","year":"2025","journal-title":"Trends Endocrinol Metab"},{"key":"R9-20261102","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41409-024-02270-x","article-title":"EASIX and cardiac adverse events after allogeneic hematopoietic cell transplantation.","volume":"59","author":"Tolosa-Ridao","year":"2024","journal-title":"Bone Marrow Transplant"},{"key":"R10-20261102","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.3390\/cancers15225443","article-title":"Population-based external validation of the EASIX scores to predict CAR T-cell-related toxicities.","volume":"15","author":"de Boer","year":"2023","journal-title":"Cancers (Basel)"},{"key":"R11-20261102","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.3390\/jpm12071022","article-title":"EASIX, modified EASIX and simplified EASIX as an early predictor for intensive care unit admission and mortality in severe COVID-19 patients.","volume":"12","author":"Zi\u0144czuk","year":"2022","journal-title":"J Pers Med"},{"key":"R12-20261102","doi-asserted-by":"crossref","first-page":"e009220","DOI":"10.1136\/jitc-2024-009220","article-title":"EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed\/refractory multiple myeloma.","volume":"12","author":"Frenking","year":"2024","journal-title":"J ImmunoTher Cancer"},{"key":"R13-20261102","doi-asserted-by":"crossref","first-page":"634416","DOI":"10.3389\/fimmu.2021.634416","article-title":"EASIX for prediction of outcome in hospitalized SARS-CoV-2 infected patients.","volume":"12","author":"Luft","year":"2021","journal-title":"Front Immunol"},{"key":"R14-20261102","doi-asserted-by":"crossref","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"147","author":"von Elm","year":"2007","journal-title":"Ann Intern Med"},{"key":"R15-20261102","doi-asserted-by":"crossref","first-page":"e414","DOI":"10.1016\/S2352-3026(17)30108-4","article-title":"EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis.","volume":"4","author":"Luft","year":"2017","journal-title":"Lancet Haematol"},{"key":"R16-20261102","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.3390\/jcm12072553","article-title":"EASIX is an accurate and easily available prognostic score in critically Ill patients with advanced liver disease.","volume":"12","author":"Schult","year":"2023","journal-title":"J Clin Med"},{"key":"R17-20261102","doi-asserted-by":"crossref","first-page":"877477","DOI":"10.3389\/fimmu.2022.877477","article-title":"EASIX and severe endothelial complications after CD19-directed CAR-T cell therapy \u2013 a cohort study.","volume":"13","author":"Korell","year":"2022","journal-title":"Front Immunol"},{"key":"R18-20261102","doi-asserted-by":"crossref","first-page":"5898","DOI":"10.1182\/bloodadvances.2022007381","article-title":"Dynamic EASIX scores closely predict nonrelapse mortality after allogeneic hematopoietic cell transplantation.","volume":"6","author":"Nawas","year":"2022","journal-title":"Blood Adv"},{"key":"R19-20261102","doi-asserted-by":"crossref","first-page":"e70057","DOI":"10.1111\/jch.70057","article-title":"Endothelial activation and stress index predicts all-cause and cardiovascular mortality in hypertensive individuals: a nationwide study.","volume":"27","author":"Dong","year":"2025","journal-title":"J Clin Hypertens (Greenwich)"},{"key":"R20-20261102","doi-asserted-by":"crossref","first-page":"23285","DOI":"10.1038\/s41598-025-06595-5","article-title":"Endothelial activation and stress index is a reliable predictor for the prevalence and mortality outcomes of stroke.","volume":"15","author":"Huang","year":"2025","journal-title":"Sci Rep"},{"key":"R21-20261102","doi-asserted-by":"crossref","first-page":"1560947","DOI":"10.3389\/fmed.2025.1560947","article-title":"Independent prognostic importance of endothelial activation and stress index (EASIX) in critically ill patients with heart failure: modulating role of inflammation.","volume":"12","author":"Yin","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"R22-20261102","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12933-018-0763-3","article-title":"Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies.","volume":"17","author":"Kaur","year":"2018","journal-title":"Cardiovasc Diabetol"},{"key":"R23-20261102","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1089\/ars.2023.0524","article-title":"Oxidative stress, endothelial dysfunction, and N-acetylcysteine in Type 2 diabetes mellitus.","volume":"40","author":"Li","year":"2024","journal-title":"Antioxid Redox Signal"},{"key":"R24-20261102","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1001\/jamacardio.2022.3926","article-title":"Fundamental pathobiology of coronary atherosclerosis and clinical implications for chronic ischemic heart disease management \u2013 the plaque hypothesis: a narrative review.","volume":"8","author":"Stone","year":"2023","journal-title":"JAMA Cardiol"},{"key":"R25-20261102","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41569-023-00877-z","article-title":"Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention.","volume":"20","author":"Wong","year":"2023","journal-title":"Nat Rev Cardiol"},{"key":"R26-20261102","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41387-024-00285-3","article-title":"Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial.","volume":"14","author":"Podadera-Herreros","year":"2024","journal-title":"Nutr Diabetes"},{"key":"R27-20261102","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s13098-023-01238-z","article-title":"Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus.","volume":"15","author":"Huang","year":"2023","journal-title":"Diabetol Metab Syndr"},{"key":"R28-20261102","doi-asserted-by":"crossref","first-page":"9985836","DOI":"10.1155\/2024\/9985836","article-title":"Sodium-glucose cotransporter-2 inhibitors and cardiovascular protection among patients with type 2 diabetes mellitus: a systematic review.","volume":"2024","author":"Yankah","year":"2024","journal-title":"J Diabetes Res"},{"key":"R29-20261102","doi-asserted-by":"crossref","first-page":"1052547","DOI":"10.3389\/fcvm.2022.1052547","article-title":"Predictive nomogram for coronary heart disease in patients with type 2 diabetes mellitus.","volume":"9","author":"Xiao","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"R30-20261102","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/s12882-024-03887-2","article-title":"Association between EASIX and acute kidney injury in critically ill cancer patients.","volume":"25","author":"Deng","year":"2024","journal-title":"BMC Nephrol"}],"container-title":["Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1097\/MD.0000000000051166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:02:06Z","timestamp":1793646126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1097\/MD.0000000000051166"}},"subtitle":["A prospective national cohort study"],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":30,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/md.0000000000051166","relation":{},"ISSN":["0025-7974","1536-5964"],"issn-type":[{"value":"0025-7974","type":"print"},{"value":"1536-5964","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-07-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}