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Comparative performance of insulin resistance-related indices in predicting adverse cardiovascular events among individuals with NAFLD and MASLD: a multi-center cohort study.

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Τίτλος: Comparative performance of insulin resistance-related indices in predicting adverse cardiovascular events among individuals with NAFLD and MASLD: a multi-center cohort study.
Συγγραφείς: Huang Y; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong, China., Xu Y; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhang C; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Gu W; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Li Y; The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China., Zhang H; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Wang T; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Su T; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Lhamu Y; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Chen Y; Pudong New District Center for Disease Control and Prevention of Shanghai, Shanghai, China.; Pudong Preventive Medicine Research Institute, Fudan University, Shanghai, China., Zhou L; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhouliang@shsmu.edu.cn., Hao L; Pudong New District Center for Disease Control and Prevention of Shanghai, Shanghai, China. hlpmail@126.com.; Pudong Preventive Medicine Research Institute, Fudan University, Shanghai, China. hlpmail@126.com., Yang Y; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yyang93@shsmu.edu.cn., Wang H; School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. huiwang@shsmu.edu.cn.
Πηγή: Cardiovascular diabetology [Cardiovasc Diabetol] 2026 Jul 04; Vol. 25 (1). Date of Electronic Publication: 2026 Jul 04.
Τύπος έκδοσης: Comparative Study; Journal Article; Multicenter Study; Observational Study
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE
Imprint Name(s): Original Publication: London : BioMed Central, [2002-
Ιατρικοί όροι (MeSH): Blood Glucose*/metabolism , Cardiovascular Diseases*/diagnosis , Cardiovascular Diseases*/epidemiology , Cardiovascular Diseases*/mortality , Metabolic Syndrome*/diagnosis , Metabolic Syndrome*/blood , Metabolic Syndrome*/epidemiology , Metabolic Syndrome*/mortality , Non-alcoholic Fatty Liver Disease*/diagnosis , Non-alcoholic Fatty Liver Disease*/blood , Non-alcoholic Fatty Liver Disease*/epidemiology , Non-alcoholic Fatty Liver Disease*/mortality , Insulin Resistance*, Biomarkers/blood ; China/epidemiology ; Inflammation Mediators/blood ; Triglycerides/blood ; United States/epidemiology ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiometabolic Risk Factors ; Nutrition Surveys ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors ; Time Factors ; UK Biobank
Περίληψη: Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and non-alcoholic fatty liver disease (NAFLD) are closely linked to insulin resistance and elevated cardiovascular risk, triglyceride-glucose (TyG)-related indices, the atherogenic index of plasma (AIP), and the cardiometabolic index (CMI) have emerged as practical surrogate markers for cardiometabolic risk assessment in these populations. However, it remains unclear whether the associations of these indices with adverse cardiovascular events remain consistent when transitioning from the NAFLD to the newly defined MASLD framework, and a comprehensive comparison of these indices across both diagnostic criteria is lacking.
Methods: This study included 4693/3266, 74,173/67,864, and 7823/10,576 individuals with MASLD/NAFLD from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKB), and China Pudong cohort, respectively. Multivariate Cox proportional hazards models, restricted cubic spline analyses, and time-dependent receiver operating characteristic curves were employed to assess associations. Linear regression models evaluated relationships between TyG-related indices and cortical/subcortical structural volumes. Mediation analyses examined the role of oxidative stress, phenotypic aging, and inflammatory markers.
Results: Most IR-related indices demonstrated nonlinear, predominantly J-shaped associations with cardiovascular disease (CVD) and related mortality, especially within the UKB. TyG-WC optimally predicted 3-year CVD mortality in MASLD/NAFLD across UKB and NHANES, as well as ischemic stroke (IS) in UKB-MASLD. TyG-WHTR was the strongest predictor for CVD mortality in the Pudong cohort and myocardial infarction (MI) in UKB-MASLD. Notably, elevated TyG-WHTR was consistently associated with heightened risks across all endpoints: CVD mortality (NAFLD: UKB: HR 1.60, 95%CI 1.38-1.84, NHANES: 1.90, 1.34-2.70, Pudong: 1.24, 1.10-1.40; MASLD: UKB: 1.59, 1.38-1.82, NHANES: 1.86, 1.36-2.54, Pudong: 1.70, 1.43-2.03), MI (NAFLD: 1.20, 1.09-1.33; MASLD: 1.22, 1.11-1.34), and IS (NAFLD: 1.41, 1.24-1.61; MASLD: 1.39, 1.23-1.57). Structural neuroimaging analyses revealed significant negative correlations between TyG-WC/TyG-WHTR and subcortical volumes (P < 1 × 10-4). Mediation analyses indicated that oxidative stress, phenotypic aging, and inflammatory markers collectively accounted for 1.4-27% of the observed associations.
Conclusions: Insulin Resistance-Related Indices demonstrate robust clinical utility in predicting CVD and mortality in NAFLD/MASLD across three distinct cohorts, with oxidative stress, inflammatory activation, and accelerated aging serving as potential mechanistic pathways.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethics approval and consent to participate: The UK Biobank received ethical approval from the North West Multi-Center Research Ethics Committee (Approved Research ID: 194423, Approval date: October 30, 2024). All participants gave written informed consent before enrollment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. The National Center for Health Statistics and Ethics Review Board approved the protocol for NHANES, and all participants provided written informed consent. Research ethics approval was obtained from the Center for Disease Control and Prevention of the Pudong New Area, Shanghai, China. Each participant provided a written consent. All participants were informed and agreed to participate in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
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Grant Information: 82403381 National Natural Science Foundation of China; 82030099 National Natural Science Foundation of China; 24YF2722700 Sailing Program of Shanghai Rising-Star Program; 2022YFD2101500 National Key R&D Program of China; 2026ZB0556800 Noncommunicable Chronic Diseases-National Science and Technology Major Project; YG2025LC14 Medical-Engineering Cross Foundation of Shanghai Jiao Tong University
Contributed Indexing: Keywords: Adverse cardiovascular events; Atherogenic index of plasma; Cardiometabolic index; Cohort study; Metabolic dysfunction-associated steatotic liver disease; Non-alcoholic fatty liver disease; Triglyceride-glucose index
Substance Nomenclature: 0 (Biomarkers)
0 (Blood Glucose)
0 (Inflammation Mediators)
0 (Triglycerides)
Entry Date(s): Date Created: 20260704 Date Completed: 20260707 Latest Revision: 20260730
Update Code: 20260731
PubMed Central ID: PMC13335360
DOI: 10.1186/s12933-026-03208-x
PMID: 42401883
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1475-2840
DOI:10.1186/s12933-026-03208-x