{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:13:24Z","timestamp":1793578404356,"version":"4.5.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dysregulation of glucolipid metabolism is a central pathological mechanism underlying acute decompensated heart failure (ADHF) and significantly impacts its poor prognosis. This study aims to investigate the association between the high-density lipoprotein cholesterol-modified triglyceride-glucose index (defined as TyG\/HDL-C) and their interaction with 30-day mortality in patients with ADHF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From 2018 to 2024, 2,329 ADHF patients enrolled in the Jiangxi-ADHF II cohort were included. Multivariable Cox regression models were utilized to evaluate the association between TyG\/HDL-C ratio and 30-day all-cause\/cardiovascular mortality risk. A 3-dimensional interaction model was employed to examine the dose-response relationships of TyG and HDL-C with mortality risk. Additionally, exploratory mediation models were constructed to investigate potential mediating effects of inflammation, oxidative stress, and nutritional metabolism in the association between TyG\/HDL-C ratio and mortality risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 30-day follow-up, 150 deaths occurred, 115 of which were cardiovascular. Multivariable Cox regression showed that each standard deviation increase in TyG\/HDL-C ratio increased 30-day all-cause mortality by 24% and cardiovascular mortality by 20%. These findings demonstrated robustness across sensitivity analyses conducted from four dimensions: model adjustment, causal timing, population heterogeneity, and data integrity. Notably, the subsequent 3-dimensional interaction model analysis revealed a complex U-shaped association \u2014 resembling a concave surface of a radio telescope \u2014 between the combined effects of TyG index and HDL-C on mortality risk. Specifically, both excessively low and high combinations of TyG index and HDL-C were associated with elevated 30-day mortality risk in ADHF patients, while the lowest mortality risk interval occurred when the TyG index remained within 7.5\u20139.0 and HDL-C levels were maintained at 1.0\u20131.5 mmol\/L. Mediation analysis further suggested that inflammatory and nutritional pathways might serve as significant mediators of mortality risk related to TyG\/HDL-C ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The TyG\/HDL-C ratio emerged as an independent predictor of short-term all-cause and cardiovascular mortality in ADHF patients, demonstrating significant enhancement in predictive performance for these outcomes. Most notably, the concave-shaped interaction pattern revealed by 3-dimensional interaction analysis provided an evidence-based threshold framework for metabolic management in ADHF patients, which may hold substantial clinical significance for reducing future mortality risks in this population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1629066","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T04:10:34Z","timestamp":1753762234000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Independent and combined associations of high-density lipoprotein cholesterol-modified triglyceride-glucose index with all-cause and cardiovascular mortality in patients with acute decompensated heart failure"],"prefix":"10.3389","volume":"16","author":[{"given":"Shiming","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoan","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengcheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guotai","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengli","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2115","article-title":"Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association","volume":"23","author":"Bozkurt","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2874","article-title":"Worsening of chronic heart failure: definition, epidemiology, management and prevention. 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