{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:16:08Z","timestamp":1781050568449,"version":"3.54.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Cardiovascular-kidney-metabolic (CKM) syndrome, driven by metabolic risk factors like obesity, type 2 diabetes (DM-2), chronic kidney disease (CKD), and cardiovascular disease (CVD), leads to poorer health outcomes. Despite its rising prevalence and promising new therapies, trends and demographic disparities in CKM-related mortality among adults in the United States remain underexplored.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methodology<\/jats:title>\n<jats:p>The study examined CDC WONDER death certificates for individuals aged 25+ who died from 1999 to 2022, with CVD as the main cause, while CKD and DM-2 as contributing factors. Age-adjusted mortality rates (AAMRs) and annual percent change (APC) were calculated by year, sex, age, race\/ethnicity, region, and urbanization status.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>From 1999 to 2022, 25,980 CKM-related deaths were recorded, with the AAMR decreasing from 5.3 to 0.4 per 1,000,000 population. AAMR rose significantly from 1999 to 2012 (APC: 7.03; p&lt;0.001), sharply declined from 2012 to 2015 (APC: -65.55; p&lt;0.001), and then increased from 2015 to 2022 (APC: 15.98; p = 0.101). Men had higher AAMRs than women (6.9 vs. 4.3), and older adults (65+) had the highest AAMR (23.3), followed by middle-aged adults (2.2). Among racial groups, non-Hispanic (NH) American Indian\/Alaska Native had the highest AAMR (11.2), followed by NH Black (8.6), Hispanic (6.6), NH White (4.8), and NH Asian\/Pacific Islander (4.7). Rural areas showed the highest AAMRs (6.8), compared to medium-small metro (6.1) and large metro areas (4.4).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>CKM-related mortality trends have varied widely over the past two decades, with men, older adults, American Indian\/Alaska Native, and non-metropolitan populations experiencing the highest AAMRs, underscoring the need for targeted interventions.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0320670","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T17:23:59Z","timestamp":1746465839000},"page":"e0320670","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Emerging trends and disparities in cardiovascular, kidney, and diabetes-related mortality: A retrospective analysis of the wide-ranging online data for epidemiologic research database"],"prefix":"10.1371","volume":"20","author":[{"given":"Aman","family":"Goyal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humza","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia Aziz","family":"Sulaiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wania","family":"Sultan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momina Riaz","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-153X","authenticated-orcid":true,"given":"Mah I.","family":"Kan Changez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Qamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarju","family":"Ganatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourbha S.","family":"Dani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"20","key":"pone.0320670.ref001","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000001186","article-title":"A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American heart association","volume":"148","author":"CE Ndumele","year":"2023","journal-title":"Circulation"},{"issue":"1","key":"pone.0320670.ref002","doi-asserted-by":"crossref","first-page":"15770","DOI":"10.1038\/s41598-024-66655-0","article-title":"Impact of chronic kidney disease and end-stage renal disease on the mid-term adverse outcomes in diabetic patients with cardiovascular diseases","volume":"14","author":"C-L Chou","year":"2024","journal-title":"Sci Rep"},{"issue":"21","key":"pone.0320670.ref003","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1001\/jama.2024.6892","article-title":"Prevalence of cardiovascular-kidney-metabolic syndrome stages in US adults, 2011-2020","volume":"331","author":"R Aggarwal","year":"2024","journal-title":"JAMA"},{"key":"pone.0320670.ref004","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","article-title":"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global burden of disease study 2013","volume":"385","author":"GBD 2013 Mortality and Causes of Death Collaborators.","year":"2015","journal-title":"Lancet"},{"issue":"1","key":"pone.0320670.ref005","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1053\/j.ajkd.2011.09.017","article-title":"Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database","volume":"59","author":"DK Packham","year":"2012","journal-title":"Am J Kidney Dis"},{"issue":"11","key":"pone.0320670.ref006","doi-asserted-by":"crossref","first-page":"412","DOI":"10.15585\/mmwr.mm7111a3","article-title":"Reported cases of end-stage kidney disease - 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