{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:26Z","timestamp":1787894306032,"version":"build-2784847793"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between baseline total cholesterol (TC) levels and incident heart failure (HF) risk in patients with atherosclerotic cardiovascular disease (ASCVD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort analysis was based on the Kailuan Study, a prospective cohort initiated in Tangshan, China. A total of 11,479 patients with first-onset ASCVD between 2006 and 2022 and available post-ASCVD TC measurements were included. Participants were classified into five TC groups: C1 (&amp;lt;3.100\u202fmmol\/L), C2 (3.100\u2013&amp;lt;4.100\u202fmmol\/L), C3 (4.100\u2013&amp;lt;5.200\u202fmmol\/L), C4 (5.200\u2013&amp;lt;6.200\u202fmmol\/L), and C5 (\u22656.200\u202fmmol\/L), with C3 as the reference. Cox proportional hazards models were used to assess HF risk. Restricted cubic spline analyses and Fine\u2013Gray subdistribution hazard models were further performed to evaluate the nonlinear association and account for the competing risk of death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During 71,406.7 person-years of follow-up, corresponding to a mean follow-up duration of 6.22\u202fyears, 610 incident HF cases occurred, with an overall incidence proportion of 5.31% and an incidence density of 8.54 per 1,000 person-years. Incidence densities from C1 to C5 were 14.35, 8.46, 7.32, 7.89, and 12.34 per 1,000 person-years, respectively. In the most comprehensively adjusted model (Model 3), which accounted for demographic characteristics, comorbidities, smoking status, body mass index, laboratory indices, medication use, and follow-up TC-related variables, C1 and C5 were associated with higher HF risk than C3, with\n                      <jats:italic>HRs<\/jats:italic>\n                      of 1.578 (\n                      <jats:italic>95% CI<\/jats:italic>\n                      1.160\u20132.148;\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.004) and 1.509 (\n                      <jats:italic>95% CI<\/jats:italic>\n                      1.150\u20131.979;\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.003), respectively. Restricted cubic spline analysis showed a significant nonlinear, approximately U-shaped association, and competing-risk analyses yielded similar findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Baseline TC levels showed a nonlinear association with incident HF risk in patients with ASCVD. High TC may reflect persistent atherogenic risk, whereas the association between low TC and HF may partly reflect residual confounding or reverse causation related to underlying comorbidities, inflammation, nutritional depletion, frailty, or lipid-lowering treatment history. Therefore, low TC should be interpreted as a potential risk marker rather than as a causal factor for HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1884333","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:31:08Z","timestamp":1787891468000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between serum total cholesterol levels and the risk of incident heart failure in patients with atherosclerotic cardiovascular disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoxiao","family":"Wang","sequence":"first","affiliation":[{"name":"The Third Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Department of Cardiology, The Affiliated Hospital of Chengde Medical College","place":["Chengde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital","place":["Tangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital","place":["Tangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tangshan Gongren Hospital","place":["Tangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Third Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Department of Cardiology, The Affiliated Hospital of North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.jacasi.2024.01.013","article-title":"Epidemiology and burden of heart failure in Asia","volume":"4","author":"Feng","year":"2024","journal-title":"JACC Asia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1016\/j.jacc.2025.09.1503","article-title":"Trends in the prevalence, associated risk factors, and health burden of heart failure in the United States, 1988 to 2023","volume":"86","author":"Sayed","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"102217","DOI":"10.1016\/j.eclinm.2023.102217","article-title":"Changing health related quality of life and outcomes in heart failure by age, sex and subtype","volume":"64","author":"Lawson","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"336","DOI":"10.5551\/jat.65908","article-title":"Lipid Management for Secondary Prevention in atherosclerotic cardiovascular disease: a scoping review and scientific report","volume":"33","author":"Tanaka","year":"2026","journal-title":"J Atheroscler Thromb"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1002\/ehf2.14521","article-title":"Differences in predictors of incident heart failure according to atherosclerotic cardiovascular disease status","volume":"10","author":"Dawson","year":"2023","journal-title":"ESC Heart Fail"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1016\/j.cjca.2024.04.017","article-title":"Dyslipidemia and the current state of cardiovascular disease: epidemiology, risk factors, and effect of lipid lowering","volume":"40","author":"Brunham","year":"2024","journal-title":"Can J Cardiol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1093\/eurjpc\/zwae102","article-title":"The role of remnant cholesterol in patients with ST-segment elevation myocardial infarction","volume":"31","author":"Zhou","year":"2024","journal-title":"Eur J Prev Cardiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.ihj.2024.10.004","article-title":"Association of non-HDL cholesterol with plaque burden and composition of culprit lesion in acute coronary syndrome. An intravascular ultrasound-virtual histology study","volume":"76","author":"Reddy","year":"2024","journal-title":"Indian Heart J"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s43556-025-00321-3","article-title":"Cholesterol metabolism: molecular mechanisms, biological functions, diseases, and therapeutic targets","volume":"6","author":"Cui","year":"2025","journal-title":"Mol Biomed"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.15420\/usc.2024.33","article-title":"Strategies for the secondary prevention of atherosclerotic cardiovascular disease","volume":"19","author":"Hurwitz","year":"2025","journal-title":"US Cardiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1016\/j.jacc.2025.04.013","article-title":"Lipoprotein(a), cholesterol, triglyceride levels, and vulnerable coronary plaques: a PROSPECT II substudy","volume":"85","author":"Erlinge","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/nu17193128","article-title":"Total cholesterol and mortality in older adults: a sex-stratified cohort study","volume":"17","author":"Iuorio","year":"2025","journal-title":"Nutrients"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.23736\/S2724-5683.24.06738-3","article-title":"Total cholesterol level decrease predicts higher mortality in chronic heart failure","volume":"73","author":"Matos","year":"2025","journal-title":"Minerva Cardiol Angiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s40119-024-00349-6","article-title":"Real-world risk of recurrent cardiovascular events in atherosclerotic cardiovascular disease patients with LDL-C above guideline-recommended threshold: a retrospective observational study","volume":"13","author":"Mackinnon","year":"2024","journal-title":"Cardiol Ther"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa2206916","article-title":"Global effect of modifiable risk factors on cardiovascular disease and mortality","volume":"389","author":"Magnussen","year":"2023","journal-title":"N Engl J Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.jacc.2023.05.035","article-title":"C-reactive protein and risk of incident heart failure in patients with cardiovascular disease","volume":"82","author":"Burger","year":"2023","journal-title":"J Am Coll Cardiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s40001-025-03825-4","article-title":"J-shaped association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and heart failure: a cross-sectional study","volume":"31","author":"Lv","year":"2026","journal-title":"Eur J Med Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.jchf.2024.03.007","article-title":"Association of high-density lipoprotein parameters and risk of heart failure: a multicohort analysis","volume":"12","author":"Pandey","year":"2024","journal-title":"JACC Heart Fail"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"105","DOI":"10.4093\/dmj.2024.0066","article-title":"Different associations between lipid levels and risk for heart failure according to diabetes progression","volume":"49","author":"Lee","year":"2025","journal-title":"Diabetes Metab J"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e034254","DOI":"10.1161\/JAHA.124.034254","article-title":"Ten-year risk equations for incident heart failure in established atherosclerotic cardiovascular disease populations","volume":"13","author":"Dawson","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e040039","DOI":"10.1161\/JAHA.124.040039","article-title":"Relationship between remnant cholesterol and risk of heart failure in a community population without cardiovascular disease: results of the China patient-Centered evaluative assessment of cardiac events million persons project","volume":"14","author":"Huang","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"247","DOI":"10.12997\/jla.2025.14.3.247","article-title":"Triglycerides, triglyceride-rich lipoproteins, and remnant cholesterol in atherosclerotic cardiovascular disease","volume":"14","author":"Jo","year":"2025","journal-title":"J Lipid Atheroscler"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111386","article-title":"Oxidized low-density lipoprotein and its role in immunometabolism","volume":"25","author":"Mosalmanzadeh","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e651","DOI":"10.1002\/mco2.651","article-title":"Endothelial dysfunction: molecular mechanisms and clinical implications","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm (2020)"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.medj.2023.12.007","article-title":"Myocardial ischemia\/reperfusion: translational pathophysiology of ischemic heart disease","volume":"5","author":"Heusch","year":"2024","journal-title":"Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3000605231202573","DOI":"10.1177\/03000605231202573","article-title":"Mechanism of heart failure after myocardial infarction","volume":"51","author":"Jiang","year":"2023","journal-title":"J Int Med Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1093\/cvr\/cvad100","article-title":"Cardiac lipid metabolism, mitochondrial function, and heart failure","volume":"119","author":"Da Dalt","year":"2023","journal-title":"Cardiovasc Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"167158","DOI":"10.1016\/j.bbadis.2024.167158","article-title":"Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity","volume":"1870","author":"Zhang","year":"2024","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3390\/cells12071042","article-title":"Palmitate-induced cardiac lipotoxicity is relieved by the redox-active motif of SELENOT through improving mitochondrial function and regulating metabolic state","volume":"12","author":"Rocca","year":"2023","journal-title":"Cells"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010858","article-title":"Canagliflozin attenuates lipotoxicity in cardiomyocytes by inhibiting inflammation and ferroptosis through activating AMPK pathway","volume":"24","author":"Zhang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s12933-024-02204-3","article-title":"Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA\/p47PHOX mediated ferroptosis","volume":"23","author":"Ni","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s10020-024-01019-y","article-title":"The interplay of factors in metabolic syndrome: understanding its roots and complexity","volume":"30","author":"Islam","year":"2024","journal-title":"Mol Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1038\/s41598-023-29276-7","article-title":"Obesity and risk for its comorbidities diabetes, hypertension, and dyslipidemia in Japanese individuals aged 65 years","volume":"13","author":"Yamada","year":"2023","journal-title":"Sci Rep"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1152\/physiol.00004.2023","article-title":"Inflammatory mechanisms in heart failure with preserved ejection fraction","volume":"38","author":"Daou","year":"2023","journal-title":"Physiology (Bethesda)"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"40939","DOI":"10.1038\/s41598-025-24832-9","article-title":"LDL cholesterol and clinical outcomes in heart failure with reduced ejection fraction: a competing risk analysis","volume":"15","author":"Wang","year":"2025","journal-title":"Sci Rep"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1002\/ehf2.15315","article-title":"Prognostic value of lipid parameters among patients with heart failure: a systematic review and meta-analysis","volume":"12","author":"Sayed","year":"2025","journal-title":"ESC Heart Fail"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/j.jchf.2024.03.003","article-title":"Controversies and conundrums in cardiac Cachexia: key questions about wasting in patients with HFrEF","volume":"12","author":"Ilonze","year":"2024","journal-title":"JACC Heart Fail"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11897-025-00711-2","article-title":"When the heart, kidneys, and body waste away: a review of Cachexia in cardiorenal syndrome","volume":"22","author":"Sarnaik","year":"2025","journal-title":"Curr Heart Fail Rep"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e89488","DOI":"10.7759\/cureus.89488","article-title":"Inflammation-driven lipid suppression in hospitalized patients: insights into the inflammatory lipid paradox from a retrospective study","volume":"17","author":"Thurmann","year":"2025","journal-title":"Cureus"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e0860","DOI":"10.1097\/CCE.0000000000000860","article-title":"Association between Hypocholesterolemia and mortality in critically ill patients with Sepsis: a systematic review and Meta-analysis","volume":"5","author":"Hofmaenner","year":"2023","journal-title":"Crit Care Explor"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s13054-025-05638-7","article-title":"Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness","volume":"29","author":"Kleyman","year":"2025","journal-title":"Crit Care"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00011-023-01845-6","article-title":"Inflammation in heart failure: pathophysiology and therapeutic strategies","volume":"73","author":"Boulet","year":"2024","journal-title":"Inflamm Res"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.3390\/nu17101736","article-title":"CONUT score as a predictor of mortality risk in acute and chronic heart failure: a Meta-analytic review","volume":"17","author":"F\u0103rca\u0219","year":"2025","journal-title":"Nutrients"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1504031","DOI":"10.3389\/fnut.2024.1504031","article-title":"Energy intake insufficiency due to underestimated energy requirement by common predictive formulas can be identified by urinary amino acid levels in advanced heart failure","volume":"11","author":"Sakamoto","year":"2025","journal-title":"Front Nutr"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1884333\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:31:13Z","timestamp":1787891473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1884333\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":45,"alternative-id":["10.3389\/fmed.2026.1884333"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1884333","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"article-number":"1884333"}}