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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BMC
2025-07-01
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| 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 |
| format | Article |
| id | doaj-art-fda8620d6cbb4d20bcd42760ce4e13ba |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| 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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