{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:03:54Z","timestamp":1784783034402,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cardiovascular-kidney-metabolic (CKM) syndrome represents an interconnected disease continuum linking metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease. Serum zinc deficiency (SZD) has been associated with adverse cardiovascular and renal outcomes; however, its association with CKM progression remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study was conducted using the TriNetX. Adults with CKM stage 1 or 2 were enrolled in the study. SZD was defined as a serum zinc concentration &amp;lt; 70 \u03bcg\/dL, while individuals with zinc concentrations between 70 and 120 \u03bcg\/dL served as controls. After 1:1 matching, 74,245 patients were included in each group. The primary outcome was operational progression from CKM stage 1\u20132 to stage 3\u20134. Secondary outcomes included major adverse cardiovascular events, coronary artery disease, peripheral artery disease, atrial fibrillation, ischemic stroke, heart failure, advanced CKD, and all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 148,490 matching individuals, SZD was associated with a significantly increased risk of operational progression to CKM stage 3\u20134 compared with normal zinc status (HR, 1.36; 95% CI, 1.30\u20131.41;\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). SZD was also associated with increased risks of other secondary outcomes (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.0056 after Bonferroni correction).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with CKM stage 1\u20132, SZD was associated with a significantly increased risk of operational progression to CKM stage 3\u20134 and a broad spectrum of adverse cardiovascular, renal, and mortality outcomes. These findings suggest that SZD may represent an important marker of adverse CKM health and may help identify individuals at increased risk for CKM progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1910233","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:28:00Z","timestamp":1784780880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum zinc deficiency and progression of cardiovascular- kidney-metabolic syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Kuan-Chieh","family":"Tu","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chi Mei Hospital","place":["Chiali, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"Department of Nutrition and Health Sciences, Chang Jung Christian University","place":["Tainan, Taiwan"]},{"name":"Department of Hospitality Management, Southern Taiwan University of Science and Technology","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chuan","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chen","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]},{"name":"Department of Intensive Care Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Min","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jheng-Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"Department of Public Health, College of Medicine, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","first-page":"e1889","DOI":"10.1016\/j.jacc.2026.03.056","article-title":"2026 AHA\/ACC\/ADA\/ASN guideline for the prevention, detection, evaluation, and management of cardiovascular-kidney-metabolic syndrome: a report of the American college of cardiology\/American heart association joint committee on clinical practice guidelines.","volume":"87","author":"Ndumele","year":"2026","journal-title":"J Am Coll Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"809","DOI":"10.17179\/excli2023-6335","article-title":"Multifunctional role of zinc in human health: an update.","volume":"22","author":"Kiouri","year":"2023","journal-title":"EXCLI J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4822","DOI":"10.3390\/ijms24054822","article-title":"Zinc: from biological functions to therapeutic potential.","volume":"24","author":"Costa","year":"2023","journal-title":"Int J Mol Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1653151","DOI":"10.3389\/fnut.2025.1653151","article-title":"Zinc deficiency predicts new-onset diabetic kidney disease in type 2 diabetes: a retrospective cohort study.","volume":"12","author":"Hung","year":"2025","journal-title":"Front Nutr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.3390\/nu17132191","article-title":"Zinc deficiency in chronic kidney disease and hemodialysis: insights from basic research to clinical implications.","volume":"17","author":"Nakatani","year":"2025","journal-title":"Nutrients."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e71609","DOI":"10.7759\/cureus.71609","article-title":"Zinc deficiency and post-acute outcomes in patients with COVID-19: a six-month retrospective cohort analysis of 3,726 patients.","volume":"16","author":"Hung","year":"2024","journal-title":"Cureus."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e63","DOI":"10.1016\/j.jinf.2023.06.021","article-title":"The association between zinc deficiency, and clinical outcomes of COVID-19.","volume":"87","author":"Wu","year":"2023","journal-title":"J Infect."},{"key":"B9","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1161\/CIRCRESAHA.123.321752","article-title":"Endothelial cell dysfunction and increased cardiovascular risk in patients with chronic kidney disease.","volume":"132","author":"Baaten","year":"2023","journal-title":"Circ Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.clnesp.2025.08.023","article-title":"The association between cardiovascular outcomes and zinc deficiency among patients with type 2 diabetes: a retrospective cohort study.","volume":"69","author":"Lin","year":"2025","journal-title":"Clin Nutr ESPEN."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e778","DOI":"10.1093\/nutrit\/nuae072","article-title":"Methods of assessment of zinc status in humans: an updated review and meta-analysis.","volume":"83","author":"Ceballos-Rasgado","year":"2025","journal-title":"Nutr Rev."},{"key":"B12","first-page":"144","article-title":"Zinc and its importance for human health: an integrative review.","volume":"18","author":"Roohani","year":"2013","journal-title":"J Res Med Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/s12011-020-02163-2","article-title":"Plasma and nail zinc concentrations, but not hair zinc, respond positively to two different forms of preventive zinc supplementation in young laotian children: a randomized controlled trial.","volume":"199","author":"Wessells","year":"2021","journal-title":"Biol Trace Elem Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1080\/27697061.2025.2461215","article-title":"Clinical outcomes in diabetic patients with zinc deficiency: a multi-institutional population-based study.","volume":"44","author":"Wu","year":"2025","journal-title":"J Am Nutr Assoc."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1589907","DOI":"10.3389\/fnut.2025.1589907","article-title":"Mortality and cardiorenal outcomes among heart failure patients with zinc deficiency: a multicenter retrospective cohort study of 8,290 patients.","volume":"12","author":"Lin","year":"2025","journal-title":"Front Nutr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"707","DOI":"10.3390\/nu8110707","article-title":"Zinc status and risk of cardiovascular diseases and type 2 diabetes mellitus-a systematic review of prospective cohort studies.","volume":"8","author":"Chu","year":"2016","journal-title":"Nutrients."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e80115","DOI":"10.1371\/journal.pone.0080115","article-title":"Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults.","volume":"8","author":"Jung","year":"2013","journal-title":"PLoS One."},{"key":"B18","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/S2215-0366(20)30462-4","article-title":"Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA.","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry."},{"key":"B19","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.4103\/sja.SJA_543_18","article-title":"The STROBE guidelines.","volume":"13","author":"Cuschieri","year":"2019","journal-title":"Saudi J Anaesth."},{"key":"B20","doi-asserted-by":"publisher","first-page":"113273","DOI":"10.1016\/j.diabres.2026.113273","article-title":"Comparative effectiveness of tirzepatide versus GLP-1 receptor agonists on cardiovascular-kidney-metabolic stage progression: a real-world cohort study.","volume":"236","author":"Wu","year":"2026","journal-title":"Diabetes Res Clin Pract."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1666887","DOI":"10.3389\/fnut.2025.1666887","article-title":"Association of zinc deficiency and risk of new-onset dementia: a retrospective cohort study.","volume":"12","author":"Huang","year":"2025","journal-title":"Front Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1655272","DOI":"10.3389\/fnut.2025.1655272","article-title":"Impact of zinc deficiency on mortality risk in patients with chronic obstructive pulmonary disease: a retrospective analysis.","volume":"12","author":"Chen","year":"2025","journal-title":"Front Nutr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1001\/jama.2015.13480","article-title":"The propensity score.","volume":"314","author":"Haukoos","year":"2015","journal-title":"JAMA."},{"key":"B24","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-value.","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1111\/opo.12131","article-title":"When to use the Bonferroni correction.","volume":"34","author":"Armstrong","year":"2014","journal-title":"Ophthalmic Physiol Opt."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1660475","DOI":"10.3389\/fnut.2025.1660475","article-title":"Zinc deficiency and risk of intracerebral hemorrhage: a retrospective cohort study.","volume":"12","author":"Chen","year":"2025","journal-title":"Front Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1658308","DOI":"10.3389\/fnut.2025.1658308","article-title":"Zinc deficiency as a contributor to acute kidney injury in patients with chronic kidney disease: a propensity score-matched retrospective analysis.","volume":"12","author":"Lai","year":"2025","journal-title":"Front Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.3390\/nu13051680","article-title":"Association of zinc deficiency with development of CVD events in patients with CKD.","volume":"13","author":"Nakatani","year":"2021","journal-title":"Nutrients."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1007\/s12011-025-04782-z","article-title":"Causal relationship between serum zinc levels and diabetic kidney disease (DKD): a plasma proteomics mediation study.","volume":"204","author":"Zhao","year":"2026","journal-title":"Biol Trace Elem Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1038\/aps.2018.25","article-title":"Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases.","volume":"39","author":"Choi","year":"2018","journal-title":"Acta Pharmacol Sin."},{"key":"B31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3390\/antiox8060164","article-title":"Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications.","volume":"8","author":"Prasad","year":"2019","journal-title":"Antioxidants."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.3390\/biom12101358","article-title":"Investigating the role of zinc in atherosclerosis: a review.","volume":"12","author":"Shen","year":"2022","journal-title":"Biomolecules."},{"key":"B33","doi-asserted-by":"publisher","first-page":"102242","DOI":"10.1016\/j.jacadv.2025.102242","article-title":"Vascular aging, cardiovascular-kidney-metabolic syndrome, and cardiovascular risk: the Northern Shanghai study.","volume":"4","author":"Shi","year":"2025","journal-title":"JACC Adv."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6039","DOI":"10.1007\/s11010-025-05379-9","article-title":"Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.","volume":"480","author":"Xu","year":"2025","journal-title":"Mol Cell Biochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"116694","DOI":"10.1016\/j.taap.2023.116694","article-title":"Diabetic cardiomyopathy - Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways.","volume":"477","author":"Cai","year":"2023","journal-title":"Toxicol Appl Pharmacol."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1910233\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:28:01Z","timestamp":1784780881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1910233\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":35,"alternative-id":["10.3389\/fnut.2026.1910233"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1910233","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1910233"}}