Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank

Abstract Background Cardiovascular–kidney–metabolic (CKM) syndrome, proposed by the American Heart Association, is strongly linked to cardiovascular disease (CVD) incidence and mortality. Triglyceride-glucose (TyG)-related indices are established predictors of CVD risk, but their associations with C...

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Main Authors: Kun Liu, Jinling Hu, Yueqing Huang, Dingliu He, Jing Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cardiovascular Diabetology
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Online Access:https://doi.org/10.1186/s12933-025-02842-1
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author Kun Liu
Jinling Hu
Yueqing Huang
Dingliu He
Jing Zhang
author_facet Kun Liu
Jinling Hu
Yueqing Huang
Dingliu He
Jing Zhang
author_sort Kun Liu
collection DOAJ
description Abstract Background Cardiovascular–kidney–metabolic (CKM) syndrome, proposed by the American Heart Association, is strongly linked to cardiovascular disease (CVD) incidence and mortality. Triglyceride-glucose (TyG)-related indices are established predictors of CVD risk, but their associations with CVD and mortality in individuals with CKM syndrome remain understudied. Methods This prospective study analyzed 282,920 UK Biobank participants with CKM syndrome stages 0–3, free of CVD at baseline. Four TyG-related indices were evaluated: TyG index, TyG-body mass index (BMI), TyG-waist circumference (TyG-WC), and TyG-waist-to-height ratio (TyG-WHtR). Outcomes, including overall CVD, coronary heart disease (CHD), stroke, all-cause mortality, and cardiovascular mortality, were identified via electronic medical records and death registries. Associations were analyzed via Cox proportional hazards and restricted cubic spline (RCS) models, with incremental predictive performance evaluated by the net reclassification index (NRI), integrated discrimination improvement (IDI), and area under the curve (AUC). Results During a median follow-up of 13.6 years, 27,134 overall CVD cases, 21,658 CHD, 6,717 strokes, 19,381 all-cause deaths, and 3,466 cardiovascular deaths occurred. Compared with the lowest quartile, the fully adjusted hazard ratios (HRs) for participants in the highest TyG quartile were 1.30 (95% CI 1.25–1.35) for overall CVD. Consistent positive associations were observed for TyG-BMI (HR: 1.49, 95% CI 1.43–1.55), TyG-WC (HR: 1.58, 95% CI 1.51–1.65), and TyG-WHtR (HR: 1.58, 95% CI 1.51–1.65). For all-cause mortality, HRs (95% CIs) in the highest versus the lowest quartile were 1.11 (1.06–1.16) for TyG-BMI, 1.24 (1.18–1.31) for TyG-WC, and 1.18 (1.13–1.24) for TyG-WHtR. Similar patterns were seen for cardiovascular mortality: TyG-BMI (HR: 1.42, 95% CI 1.27–1.59); TyG-WC(HR: 1.51, 95% CI 1.33–1.72); TyG-WHtR (HR: 1.48, 95% CI 1.31–1.67). RCS analyses revealed nonlinear associations between TyG-related indices and overall CVD (all P values for nonlinearity < 0.05), except for the TyG index, which showed a linear trend. Associations with cardiovascular mortality were predominantly linear. Furthermore, TyG-WHtR, TyG-WC, and TyG-BMI exhibited significantly higher NRI, IDI, and AUC values. Conclusion Higher TyG-related indices, especially TyG-BMI, TyG-WC, and TyG-WHtR, were significantly associated with a higher risk of incident CVD and mortality in individuals with CKM syndrome stage 0 to 3. Integrating TyG indices with obesity measures could enhance the incremental predictive performance for prognostic outcomes in CKM syndrome patients. Graphical abstract
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spelling doaj-art-fda8620d6cbb4d20bcd42760ce4e13ba2025-08-20T03:45:44ZengBMCCardiovascular Diabetology1475-28402025-07-0124111710.1186/s12933-025-02842-1Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK BiobankKun Liu0Jinling Hu1Yueqing Huang2Dingliu He3Jing Zhang4Department of Anesthesiology, Shengjing Hospital of China Medical UniversityDepartment of Ultrasound, Shengjing Hospital of China Medical UniversityDepartments of General Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical UniversityDepartment of Clinical Nutrition, Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of YanchengDepartment of Ultrasound, Shengjing Hospital of China Medical UniversityAbstract Background Cardiovascular–kidney–metabolic (CKM) syndrome, proposed by the American Heart Association, is strongly linked to cardiovascular disease (CVD) incidence and mortality. Triglyceride-glucose (TyG)-related indices are established predictors of CVD risk, but their associations with CVD and mortality in individuals with CKM syndrome remain understudied. Methods This prospective study analyzed 282,920 UK Biobank participants with CKM syndrome stages 0–3, free of CVD at baseline. Four TyG-related indices were evaluated: TyG index, TyG-body mass index (BMI), TyG-waist circumference (TyG-WC), and TyG-waist-to-height ratio (TyG-WHtR). Outcomes, including overall CVD, coronary heart disease (CHD), stroke, all-cause mortality, and cardiovascular mortality, were identified via electronic medical records and death registries. Associations were analyzed via Cox proportional hazards and restricted cubic spline (RCS) models, with incremental predictive performance evaluated by the net reclassification index (NRI), integrated discrimination improvement (IDI), and area under the curve (AUC). Results During a median follow-up of 13.6 years, 27,134 overall CVD cases, 21,658 CHD, 6,717 strokes, 19,381 all-cause deaths, and 3,466 cardiovascular deaths occurred. Compared with the lowest quartile, the fully adjusted hazard ratios (HRs) for participants in the highest TyG quartile were 1.30 (95% CI 1.25–1.35) for overall CVD. Consistent positive associations were observed for TyG-BMI (HR: 1.49, 95% CI 1.43–1.55), TyG-WC (HR: 1.58, 95% CI 1.51–1.65), and TyG-WHtR (HR: 1.58, 95% CI 1.51–1.65). For all-cause mortality, HRs (95% CIs) in the highest versus the lowest quartile were 1.11 (1.06–1.16) for TyG-BMI, 1.24 (1.18–1.31) for TyG-WC, and 1.18 (1.13–1.24) for TyG-WHtR. Similar patterns were seen for cardiovascular mortality: TyG-BMI (HR: 1.42, 95% CI 1.27–1.59); TyG-WC(HR: 1.51, 95% CI 1.33–1.72); TyG-WHtR (HR: 1.48, 95% CI 1.31–1.67). RCS analyses revealed nonlinear associations between TyG-related indices and overall CVD (all P values for nonlinearity < 0.05), except for the TyG index, which showed a linear trend. Associations with cardiovascular mortality were predominantly linear. Furthermore, TyG-WHtR, TyG-WC, and TyG-BMI exhibited significantly higher NRI, IDI, and AUC values. Conclusion Higher TyG-related indices, especially TyG-BMI, TyG-WC, and TyG-WHtR, were significantly associated with a higher risk of incident CVD and mortality in individuals with CKM syndrome stage 0 to 3. Integrating TyG indices with obesity measures could enhance the incremental predictive performance for prognostic outcomes in CKM syndrome patients. Graphical abstracthttps://doi.org/10.1186/s12933-025-02842-1Cardiovascular–kidney–metabolic syndromeTriglyceride-glucose indexWaist-to-height ratioWaist circumferenceBody mass indexCardiovascular disease
spellingShingle Kun Liu
Jinling Hu
Yueqing Huang
Dingliu He
Jing Zhang
Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
Cardiovascular Diabetology
Cardiovascular–kidney–metabolic syndrome
Triglyceride-glucose index
Waist-to-height ratio
Waist circumference
Body mass index
Cardiovascular disease
title Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
title_full Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
title_fullStr Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
title_full_unstemmed Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
title_short Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3: a prospective cohort study of 282,920 participants in the UK Biobank
title_sort triglyceride glucose related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular kidney metabolic ckm syndrome stages 0 3 a prospective cohort study of 282 920 participants in the uk biobank
topic Cardiovascular–kidney–metabolic syndrome
Triglyceride-glucose index
Waist-to-height ratio
Waist circumference
Body mass index
Cardiovascular disease
url https://doi.org/10.1186/s12933-025-02842-1
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