Blood fat and sugar-related measures linked to heart disease and death risk in people with early to moderate cardiovascular, kidney, and metabolic problems
During a median follow-up of 13.6 years, 27,134 overall cardiovascular disease (CVD) cases were recorded among 282,920 participants with cardiovascular-kidney-metabolic () syndrome.
Higher quartiles of triglyceride-glucose ()-related indices are associated with an increased risk of overall CVD, with hazard ratios ranging from 1.30 to 1.58 for the highest quartile compared to the lowest.
The TyG-body mass index (BMI), TyG-waist circumference (WC), and TyG-waist-to-height ratio (WHtR) show consistent positive associations with all-cause and cardiovascular mortality.
For all-cause mortality, hazard ratios for the highest versus lowest quartiles of TyG-BMI, TyG-WC, and TyG-WHtR were 1.11, 1.24, and 1.18, respectively.
Nonlinear associations between TyG-related indices and overall CVD were observed, particularly for TyG-WC and TyG-BMI, while cardiovascular mortality showed predominantly linear associations.
Integrating TyG indices with obesity measures may enhance predictive performance for prognostic outcomes in CKM syndrome patients.
Simplified
BACKGROUND: Cardiovascular-kidney-metabolic () syndrome, proposed by the American Heart Association, is strongly linked to cardiovascular disease (CVD) incidence and mortality. Triglyceride-glucose ()-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.
Key numbers
1.58×
Increase in CVD risk
Hazard ratio for overall CVD in highest vs. lowest -WC quartile.
1.24
Increase in all-cause mortality risk
Hazard ratio for all-cause mortality in highest vs. lowest -WC quartile.
282,920
Study population size
Total number of participants analyzed in the study.
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Declarations. Ethics approval and consent to participate: The Northwest Multi-center Research Ethics Committee (MREC reference: 21/NW/0157) provided ethical approval for the UK Biobank project. All participants gave informed consent before being recruited. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
