{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:00Z","timestamp":1787026320124,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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. Cardiovasc. Med."],"abstract":"\n Objective<\/jats:title>\n YKL-40, previously known as chitinase-3-like protein 1 (CHI3L1), is an inflammation-related glycoprotein that promotes atherosclerosis, but its application and optimal cut-off value as a prognostic biomarker in coronary heart disease (CHD) require more clinical evidence. Thus, this prospective study aimed to evaluate the linkage of serum YKL-40 with disease features, inflammatory cytokines, and major adverse cardiovascular events (MACEs) in CHD patients.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A total of 410 CHD patients were enrolled for serum YKL-40 determination via enzyme-linked immunosorbent assay. Meanwhile, serum YKL-40 levels in 100 healthy controls (HCs) were also quantified.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n YKL-40 level was higher in CHD patients compared with that in HCs (\n P\u2009<\/jats:italic>\n &lt;\u20090.001). YKL-40 was positively linked with hyperlipidemia (\n P\u2009<\/jats:italic>\n =\u20090.014), diabetes mellitus (\n P\u2009<\/jats:italic>\n =\u20090.001), fasting blood glucose (\n P\u2009<\/jats:italic>\n =\u20090.045), C-reactive protein (\n P\u2009<\/jats:italic>\n &lt;\u20090.001), the Gensini score (\n P\u2009<\/jats:italic>\n &lt;\u20090.001), and stenosis degree (graded by the Gensini score) (\n P\u2009<\/jats:italic>\n &lt;\u20090.001) in CHD patients. In addition, an elevated YKL-40 level was associated with increased levels of tumor necrosis factor alpha (\n P\u2009<\/jats:italic>\n =\u20090.001), interleukin (IL)-1\u03b2 (\n P\u2009<\/jats:italic>\n =\u20090.001), IL-6 (\n P\u2009<\/jats:italic>\n &lt;\u20090.001), and IL-17A (\n P\u2009<\/jats:italic>\n =\u20090.002) in CHD patients. The 1-\/2-\/3-year cumulative MACE rates of CHD patients were 5.5%, 14.4%, and 25.0%, respectively. Regarding the prognostic capability, YKL-40 \u2265100\u2005ng\/ml (the median cut-off value) (\n P\u2009<\/jats:italic>\n =\u20090.003) and YKL-40 \u2265150\u2005ng\/ml (the third interquartile cut-off value) (\n P\u2009<\/jats:italic>\n =\u20090.021) reflected an elevated accumulating MACE rate, whereas accumulating MACE was not different between CHD patients with YKL-40 \u226580 and &lt;80\u2005ng\/ml (the first interquartile cut-off value) (\n P\u2009<\/jats:italic>\n =\u20090.083).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Serum YKL-40 is positively linked with inflammatory cytokines and the Gensini score, whose high expression cut-off by 100 and 150\u2005ng\/ml estimates a higher MACE risk in CHD patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcvm.2023.1242339","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T06:25:18Z","timestamp":1698733518000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Serum YKL-40 in coronary heart disease: linkage with inflammatory cytokines, artery stenosis, and optimal cut-off value for estimating major adverse cardiovascular events"],"prefix":"10.3389","volume":"10","author":[{"given":"Mowei","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erjun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e185","DOI":"10.1161\/ATVBAHA.120.313608","article-title":"Coronary artery disease","volume":"40","author":"Agrawal","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.2991\/jegh.k.201217.001","article-title":"Epidemiology and the magnitude of coronary artery disease and acute coronary syndrome: a narrative review","volume":"11","author":"Ralapanawa","year":"2021","journal-title":"J Epidemiol Glob Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-981-15-2517-9_1","article-title":"Coronary artery disease: from mechanism to clinical practice","volume":"1177","author":"Shao","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1093\/cvr\/cvab303","article-title":"Inflammation during the life cycle of the atherosclerotic plaque","volume":"117","author":"Libby","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3850","DOI":"10.3390\/ijms22083850","article-title":"Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches","volume":"22","author":"Medina-Leyte","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1161\/CIRCULATIONAHA.120.049755","article-title":"Outcomes in the ISCHEMIA trial based on coronary artery disease and ischemia severity","volume":"144","author":"Reynolds","year":"2021","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1001\/jamainternmed.2013.12855","article-title":"Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials","volume":"174","author":"Stergiopoulos","year":"2014","journal-title":"JAMA Intern Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41392-020-00303-7","article-title":"Chitinase-3 like-protein-1 function and its role in diseases","volume":"5","author":"Zhao","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1007\/s00380-019-01434-w","article-title":"YKL-40 promotes the progress of atherosclerosis independent of lipid metabolism in apolipoprotein E(\u2212\/\u2212) mice fed a high-fat diet","volume":"34","author":"Chen","year":"2019","journal-title":"Heart Vessels"},{"key":"B10","doi-asserted-by":"publisher","first-page":"749","DOI":"10.7150\/thno.20183","article-title":"Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice","volume":"8","author":"Jung","year":"2018","journal-title":"Theranostics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/jcla.21804","article-title":"Diagnostic value of serum YKL-40 level for coronary artery disease: a meta-analysis","volume":"30","author":"Song","year":"2016","journal-title":"J Clin Lab Anal"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4905954","DOI":"10.1155\/2022\/4905954","article-title":"The value of serum YKL-40 and TNF-alpha in the diagnosis of acute ST-segment elevation myocardial infarction","volume":"2022","author":"Fang","year":"2022","journal-title":"Cardiol Res Pract"},{"key":"B13","doi-asserted-by":"publisher","first-page":"644","DOI":"10.20452\/pamw.4345","article-title":"Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score","volume":"128","author":"Sciborski","year":"2018","journal-title":"Pol Arch Intern Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2217\/bmm-2016-0240","article-title":"High serum YKL-40 level positively correlates with coronary artery disease","volume":"11","author":"Jin","year":"2017","journal-title":"Biomark Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e014634","DOI":"10.1161\/JAHA.119.014634","article-title":"Prognosis and reclassification by YKL-40 in stable coronary artery disease","volume":"9","author":"Schroder","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B16","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/s00059-012-3671-4","article-title":"Elevated serum YKL-40 level predicts myocardial reperfusion and in-hospital MACE in patients with STEMI","volume":"38","author":"Cetin","year":"2013","journal-title":"Herz"},{"key":"B17","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.imbio.2012.10.015","article-title":"Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: a prognostic study within the CLARICOR trial","volume":"218","author":"Harutyunyan","year":"2013","journal-title":"Immunobiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/S0002-9149(83)80105-2","article-title":"A more meaningful scoring system for determining the severity of coronary heart disease","volume":"51","author":"Gensini","year":"1983","journal-title":"Am J Cardiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1001\/jama.2016.12680","article-title":"Effect of care guided by cardiovascular magnetic resonance, myocardial perfusion scintigraphy, or NICE guidelines on subsequent unnecessary angiography rates: the CE-MARC 2 randomized clinical trial","volume":"316","author":"Greenwood","year":"2016","journal-title":"JAMA"},{"key":"B20","first-page":"953","article-title":"Increased serum YKL-40 level is associated with the presence and severity of metabolic syndrome","volume":"16","author":"Akboga","year":"2016","journal-title":"Anatol J Cardiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"108384","DOI":"10.1016\/j.jdiacomp.2022.108384","article-title":"Triglyceride content of lipoprotein subclasses and kidney hemodynamic function and injury in adolescents with type 1 diabetes","volume":"37","author":"Pauley","year":"2023","journal-title":"J Diabetes Complications"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.3390\/ijms21051835","article-title":"The diabetes mellitus-atherosclerosis connection: the role of lipid and glucose metabolism and chronic inflammation","volume":"21","author":"Poznyak","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1111\/jocd.13124","article-title":"Serum YKL40: a novel potential link between inflammation and dyslipidemia in acne vulgaris","volume":"19","author":"Ebrahim","year":"2020","journal-title":"J Cosmet Dermatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1159\/000444855","article-title":"Chitinase 3 like-1: an emerging molecule involved in diabetes and diabetic complications","volume":"83","author":"Di Rosa","year":"2016","journal-title":"Pathobiology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3390\/cells10020201","article-title":"Role of chitinase 3-like 1 protein in the pathogenesis of hepatic insulin resistance in nonalcoholic fatty liver disease","volume":"10","author":"Zhang","year":"2021","journal-title":"Cells"},{"key":"B26","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.cca.2020.09.035","article-title":"YKL-40 as a novel biomarker in cardio-metabolic disorders and inflammatory diseases","volume":"511","author":"Deng","year":"2020","journal-title":"Clin Chim Acta"},{"key":"B27","doi-asserted-by":"publisher","first-page":"752773","DOI":"10.3389\/fcell.2021.752773","article-title":"YKL-40 aggravates early-stage atherosclerosis by inhibiting macrophage apoptosis in an aven-dependent way","volume":"9","author":"Huan","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00011-006-0076-y","article-title":"YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis","volume":"55","author":"Rathcke","year":"2006","journal-title":"Inflamm Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"adv00646","DOI":"10.2340\/actadv.v101.978","article-title":"Chitinase-3-like protein 1 (YKL-40): a new biomarker of inflammation in pyoderma gangrenosum","volume":"102","author":"Jankowska-Konsur","year":"2022","journal-title":"Acta Derm Venereol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e14606","DOI":"10.1111\/dth.14606","article-title":"Serum YKL-40 and IL 17 in psoriasis: reliability as prognostic markers for disease severity and responsiveness to treatment","volume":"34","author":"Khashaba","year":"2021","journal-title":"Dermatol Ther"},{"key":"B31","doi-asserted-by":"publisher","first-page":"438","DOI":"10.4049\/jimmunol.1201827","article-title":"YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-kappaB pathways, causing bronchial smooth muscle proliferation and migration","volume":"190","author":"Tang","year":"2013","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"6989","DOI":"10.7150\/thno.75069","article-title":"Chitinase-3 like-protein-1 promotes glioma progression via the NF-kappaB signaling pathway and tumor microenvironment reprogramming","volume":"12","author":"Zhao","year":"2022","journal-title":"Theranostics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1093\/clinchem\/hvaa275","article-title":"Inflammation in atherosclerosis-no longer a theory","volume":"67","author":"Libby","year":"2021","journal-title":"Clin Chem"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1161\/CIRCRESAHA.121.319077","article-title":"Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease","volume":"128","author":"Ridker","year":"2021","journal-title":"Circ Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e006643","DOI":"10.1161\/CIRCHEARTFAILURE.119.006643","article-title":"YKL-40 (chitinase-3-like protein 1) serum levels in aortic stenosis","volume":"13","author":"Arain","year":"2020","journal-title":"Circ Heart Fail"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e1003513","DOI":"10.1371\/journal.pmed.1003513","article-title":"Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: a retrospective study","volume":"18","author":"Wallentin","year":"2021","journal-title":"PLoS Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.atherosclerosis.2018.05.006","article-title":"YKL-40 levels increase with declining ankle-brachial index and are associated with long-term cardiovascular mortality in peripheral arterial disease patients","volume":"274","author":"Hobaus","year":"2018","journal-title":"Atherosclerosis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1093\/cvr\/cvab014","article-title":"Chitinase 3 like 1 is a regulator of smooth muscle cell physiology and atherosclerotic lesion stability","volume":"117","author":"Tsantilas","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/s12883-022-03000-w","article-title":"Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke","volume":"22","author":"Zhang","year":"2022","journal-title":"BMC Neurol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2147\/CIA.S98151","article-title":"The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population","volume":"11","author":"Zhu","year":"2016","journal-title":"Clin Interv Aging"},{"key":"B41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1097\/XCE.0000000000000073","article-title":"The inflammatory biomarker YKL-40 decreases stepwise after exercise stress test","volume":"5","author":"Mygind","year":"2016","journal-title":"Cardiovasc Endocrinol"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1242339\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T06:25:21Z","timestamp":1698733521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1242339\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":41,"alternative-id":["10.3389\/fcvm.2023.1242339"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1242339","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"article-number":"1242339"}}