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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

Kun Liu, Jin-Lin Hu, Yueqing Huang, Dingliu He, Jing Zhang

Cardiovascular Diabetology, 2025

282,920 participants · 66 citations

Abstract

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. 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). 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),…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 282,920 participants or records.

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