{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:30:53Z","timestamp":1786336253490,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cardiometabolic multimorbidity (CMM) has become a major global public health challenge. Although dyslipidemia and chronic low-grade inflammation are known to contribute to cardiometabolic diseases, their long-term cumulative combined effects on the risk of CMM remain poorly understood. This study aimed to evaluate the associations of cumulative lipid-inflammatory indices with incident CMM in a large prospective cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 25,376 participants from the Kailuan cohort were included and followed up until December 31, 2023. Nine cumulative lipid-inflammatory exposure indices were constructed via trapezoidal area-under-the-curve calculation using repeated measurements from 2006 to 2010. The primary outcome was incident CMM, defined as the concurrence of at least two cardiometabolic diseases including type 2 diabetes, ischemic heart disease and stroke. Multivariable Cox regression, restricted cubic spline analyses, competing-risk models, and subgroup analyses were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During a median follow-up of 13.0 years, 481 incident CMM events were documented. All nine cumulative lipid-inflammatory indices were independently and positively associated with an elevated risk of CMM in a dose-response manner. Incorporating these indices into conventional risk model improved risk reclassification and discriminatory ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated cumulative lipid-inflammatory indices are associated with a higher risk of incident CMM. These composite markers may serve as auxiliary indicators for preliminary risk stratification, while causal relationships cannot be confirmed based on this observational cohort alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1909025","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:21:35Z","timestamp":1786335695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cumulative lipid\u2013inflammatory indices and the risk of cardiometabolic multimorbidity: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Lijun","family":"Meng","sequence":"first","affiliation":[{"name":"Graduate School, Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Affiliated Hospital of North China University of Science and Technology","place":["Tangshan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tangshan Gongren Hospital","place":["Tangshan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital","place":["Tangshan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital","place":["Tangshan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kailuan General Hospital","place":["Tangshan, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Affiliated Hospital of North China University of Science and Technology","place":["Tangshan, Hebei, China"]},{"name":"The Third Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-01858-9","article-title":"Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants","volume":"22","author":"Han","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.puhe.2024.12.041","article-title":"Trends in the prevalence of cardiometabolic diseases in US adults with newly diagnosed and undiagnosed diabetes, 1988\u20132020","volume":"239","author":"Shi","year":"2025","journal-title":"Public Health"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114790","article-title":"Long-term exposure to PM2.5 and O3 with cardiometabolic multimorbidity: evidence among Chinese elderly population from 462 cities","volume":"255","author":"Su","year":"2023","journal-title":"Ecotoxicology Environ Saf"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-7216-0284-4.50012-9","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2009.166017","article-title":"Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis is associated with necrotic core plaques","volume":"95","author":"Lavi","year":"2009","journal-title":"Heart"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.22.1_supplement.471.11","article-title":"Endothelial cell dysfunction and the pathobiology of atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s41043-026-01289-8","article-title":"Cumulative inflammatory index and the risk of cardiometabolic multimorbidity: a prospective cohort study among middle-aged and older adults in China","volume":"45","author":"Li","year":"2026","journal-title":"J Health Popul Nutr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0340098","article-title":"C-reactive protein-triglyceride-glucose index versus triglyceride-glucose index in predicting cardiovascular metabolic multimorbidity risk: a cohort study","volume":"21","author":"Chu","year":"2026","journal-title":"PloS One"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000065636.15310.9c","article-title":"C-reactive protein is independently associated with fasting insulin in nondiabetic women","volume":"23","author":"Pradhan","year":"2003","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12944-025-02850-w","article-title":"Cumulative average remnant cholesterol inflammatory index and risk of cardiometabolic multimorbidity: evidence from a prospective nationwide cohort study in China","volume":"25","author":"Zhang","year":"2026","journal-title":"Lipids Health Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.4758","article-title":"Association of trajectory of cardiovascular health score and incident cardiovascular disease","volume":"2","author":"Wu","year":"2019","journal-title":"JAMA Netw Open"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-0591-1_12","article-title":"Association of age of onset of hypertension with cardiovascular diseases and mortality","volume":"75","author":"Wang","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/circoutcomes.111.963694","article-title":"Prevalence of ideal cardiovascular health and its relationship with the 4-year cardiovascular events in a northern Chinese industrial city","volume":"5","author":"Wu","year":"2012","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.16439\/j.issn.1673-7245.2022.03.008","article-title":"Impact of cumulative exposure to fasting plasma glucose on cardiovascular and cerebrovascular events","volume":"30","author":"Liu","year":"2022","journal-title":"Chin J Hypertens"},{"key":"B16","article-title":"Effect of non-high-density lipoprotein cholesterol on cardiovascular disease in postmenopausal women","volume":"39","author":"Zhang","year":"2024","journal-title":"Chin Circ J"},{"key":"B17","article-title":"Chinese expert consensus on medical nutrition therapy for overweight\/obesity (2016 edition)","volume":"8","year":"2016","journal-title":"Chin J Diabetes"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.2007.s133","article-title":"Chinese guidelines for the prevention and treatment of type 2 diabetes (2020 edition)","volume":"37","year":"2021","journal-title":"Chin J Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","first-page":"603","DOI":"10.16439\/j.issn.1673-7245.2024.07.002","article-title":"Chinese hypertension guideline (2024 revision)","volume":"32","year":"2024","journal-title":"Chin J Hypertens"},{"key":"B20","article-title":"Chinese guidelines for lipid management (primary care edition 2024)","volume":"52","year":"2024","journal-title":"Chin J Cardiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.11.029","article-title":"Non-traditional lipid-inflammatory parameters estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study","author":"Huang","year":"2025","journal-title":"J Adv Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12916-024-03536-3","article-title":"The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999-2018","volume":"22","author":"Yu","year":"2024","journal-title":"BMC Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14343","article-title":"A novel index for diagnosis of type 2 diabetes mellitus: cholesterol, high density lipoprotein, and glucose (CHG) index","volume":"16","author":"Mansoori","year":"2024","journal-title":"J Diabetes Invest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-025-02650-2","article-title":"Remnant cholesterol inflammatory index, calculated from residual cholesterol to C-reactive protein ratio, and stroke outcomes: a retrospective study using the National Institutes of Health Stroke Scale and modified Rankin scale","volume":"24","author":"Yu","year":"2025","journal-title":"Lipids Health Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-025-02742-z","article-title":"Evaluation of a new TyG indicator, TyHGB, in predicting non-alcoholic fatty liver disease: evidence from two independent populations","volume":"24","author":"Zhao","year":"2025","journal-title":"Lipids Health Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-52488-6","article-title":"C-reactive protein-triglyceride-glucose index (CTI) as a predictor of chronic liver disease in adults with macrocytic anemia","author":"Shang","year":"2026","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2026.1836149","article-title":"Association of the hs-CRP-TyG index with coronary artery disease risk and angiographic severity: a retrospective comparative study with the TyG index","volume":"17","author":"Yang","year":"2026","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-026-03208-x","article-title":"Comparative performance of insulin resistance-related indices in predicting adverse cardiovascular events among individuals with NAFLD and MASLD: a multi-center cohort study","volume":"25","author":"Huang","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-026-03260-7","article-title":"Associations between the C-reactive protein-triglyceride-glucose index and its derived indices and the incidence and progression of cardiometabolic multimorbidity in participants with metabolic dysfunction-associated steatotic liver disease: a large-scale prospective cohort study","author":"Tian","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1186\/s12933-025-02960-w","article-title":"The relationship between C-reactive protein-triglyceride-glucose index and cardiovascular disease: insights from the China health and retirement longitudinal study (CHARLS)","volume":"24","author":"Zhang","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s12933-025-02928-w","article-title":"Associations of six insulin resistance-related indices with the risk and progression of cardio-renal-metabolic multimorbidity: evidence from the UK biobank","volume":"24","author":"Liu","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-026-00309-0","article-title":"Decoding the lipid etiology of atherogenic index of plasma and gout: establishing the causal role of triglycerides through NHANES, Mendelian randomization, and network pharmacology","volume":"12","author":"Tian","year":"2026","journal-title":"Cardiovasc Diabetol Endocrinol Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae034","article-title":"Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials","volume":"120","author":"Xie","year":"2024","journal-title":"Cardiovasc Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1280185","article-title":"Serum\/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis","volume":"11","author":"Jin","year":"2023","journal-title":"Front Public Health"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.768119","article-title":"Obesity and cardiovascular disease: the emerging role of inflammation","volume":"8","author":"Khafagy","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-026-02904-7","article-title":"The combined effects of cardiometabolic index and high sensitivity C-reactive protein on cardiometabolic multimorbidity risk: a prospective analysis based on CHARLS","volume":"25","author":"Hua","year":"2026","journal-title":"Lipids Health Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"54","author":"Libby","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-02115-9","article-title":"The association between triglyceride-glucose index and its combination with obesity indicators and cardiovascular disease: NHANES 2003\u20132018","volume":"23","author":"Dang","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-026-03155-7","article-title":"Associations of cumulative exposure and dynamic trajectories of the triglyceride\u2013total cholesterol\u2013body weight index with new-onset cardiometabolic multimorbidity in middle-aged and older Chinese adults: evidence from a nationwide prospective cohort study","volume":"25","author":"Chen","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02244-9","article-title":"Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study","volume":"23","author":"Cui","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/289645","article-title":"Chronic inflammation in obesity and the metabolic syndrome","volume":"2010","author":"Monteiro","year":"2010","journal-title":"Mediators Inflammation"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nm1372","article-title":"Induction of leptin resistance through direct interaction of C-reactive protein with leptin","volume":"12","author":"Chen","year":"2006","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.jacc.2013.05.016","article-title":"High-sensitivity C-reactive protein and cardiovascular disease","volume":"62","author":"Yousuf","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135846","article-title":"Macrophages, inflammation, and insulin resistance","volume":"72","author":"Olefsky","year":"2010","journal-title":"Annu Rev Physiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.123.039381","article-title":"Unsupervised learning analysis of triglycerides, inflammation, cholesterol, and the risks of incident cardiovascular disease and type 2 diabetes in the women's health study","volume":"14","author":"Duran","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2026.1822659","article-title":"Adipose tissue distribution in metabolic disease: depot-specific biology, clinical assessment, and therapeutic remodeling","volume":"17","author":"LiuLi","year":"2026","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-025-02961-9","article-title":"Insulin resistance-related indices, genetic risk, and the risk of cardiovascular disease in individuals with preclinical or clinical obesity: a large prospective cohort study in the UK biobank","volume":"24","author":"Hu","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-026-03177-1","article-title":"Cardiovascular-kidney-metabolic syndrome: a comprehensive review of pathophysiology, epidemiology, diagnosis, and management","volume":"25","author":"Jankauskas","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1618157","article-title":"Association of the atherogenic index of plasma and high-sensitivity C-reactive protein with incident cardiovascular disease: evidence from a national cohort of middle-aged and older Chinese adults","volume":"16","author":"Lian","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-026-02953-y","article-title":"Association between the triglyceride-high-density lipoprotein-glucose-body index and new-onset stroke risk: a prospective cohort study","author":"Lu","year":"2026","journal-title":"Lipids Health Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-026-03191-3","article-title":"The association between triglyceride glucose-frailty index and cardiometabolic multimorbidity among Chinese middle-aged and older adults: a national prospective cohort study","author":"Hou","year":"2026","journal-title":"Cardiovasc Diabetol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/s13690-025-01762-6","article-title":"Improving cardiometabolic multimorbidity prediction with a composite obesity-TyG index: a study of middle-aged and older adults in CHARLS","volume":"83","author":"Wang","year":"2025","journal-title":"Arch Public Health"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-026-00283-7","article-title":"Epidemiology of cardiovascular disease and diabetes in 2026: expanding prevalence, escalating costs, and the limits of contemporary prevention","volume":"12","author":"Santulli","year":"2026","journal-title":"Cardiovasc Diabetol Endocrinol Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s40842-026-00293-5","article-title":"Clinical characteristics and outcomes of diabetic ketoacidosis in patients with type 2 diabetes during acute systemic stress","volume":"12","author":"Mohamed","year":"2026","journal-title":"Cardiovasc Diabetol Endocrinol Rep"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1909025\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:21:37Z","timestamp":1786335697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1909025\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":54,"alternative-id":["10.3389\/fendo.2026.1909025"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1909025","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1909025"}}