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. 2025 Jul 1;15(1):21464.
doi: 10.1038/s41598-025-06770-8.

Combined association of triglyceride-glucose index and systemic inflammation index on all-cause and cardiovascular mortality

Guanglei Liu #  1 , Rise Zheng #  2 , Qingyue Zeng #  2 , Shuangqing Li  3 , Zhenmei An  4
Affiliations

Combined association of triglyceride-glucose index and systemic inflammation index on all-cause and cardiovascular mortality

Guanglei Liu et al. Sci Rep. .

Abstract

The triglyceride-glucose and systemic inflammation index have been linked to mortality outcomes. However, their combined impact on all-cause and cardiovascular mortality remains unclear. This study aimed to evaluate the individual and combined associations of the TyG index and SII with mortality using data from NHANES. Associations between TyG, SII, and mortality were assessed using multivariable Cox proportional hazards models and restricted cubic spline (RCS) regression models. Subgroup and sensitivity analyses were also conducted. Compared to individuals with low TyG and low SII, those with high TyG and high SII had a hazard ratio (HR) of 1.29 (95% CI, 1.16-1.44) for all-cause mortality, 1.54 (95% CI, 1.23-1.94) for cardiovascular mortality, 1.56 (95% CI, 1.20-2.04) for cardiac mortality, and 1.60 (95% CI, 0.83-3.08) for cerebrovascular mortality after full adjustment. The ROC curve analysis indicated that the combination of TyG and SII had an AUC of 0.599 for predicting all-cause mortality and 0.613 for cardiovascular mortality. Subgroup and sensitivity analyses yielded consistent findings. In conclusion, these results underscore the significant combined association of the TyG index and SII on all-cause and cardiovascular mortality, highlighting the importance of jointly assessing these indices to better predict mortality outcomes.

Keywords: Inflammation; Insulin resistance; Mortality; Systemic inflammation index; Triglyceride–glucose index.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was performed according to the guidelines of the Helsinki Declaration. Consent to participate was obtained and the National Center for Health Statistics ethics committee approved the protocol of the NHANES study. The data is publicly available, therefore, the ethical approval statement and the requirement for informed consent were waived for this study.

Figures

Fig. 1
Fig. 1
Flowchart of the selection strategy. TyG triglyceride–glucose index, SII Systemic Inflammation Index, DM diabetes, CVD cardiovascular disease.
Fig. 2
Fig. 2
Forest plot showing the association of TyG and SII with mortality. This forest plot presents the HRs with 95% CIs for mortality according to TyG and SII levels, using Q1 as the reference group. HR hazard ratio, CI confdence interval, TyG triglyceride–glucose index, SII Systemic Inflammation Index. (A) Association of TyG with the risk of mortality; (B) association of SII with the risk of mortality. The event column represents the number of individuals with positive outcomes.
Fig. 3
Fig. 3
Forest plot showing the association of joint effect with mortality. This forest plot presents the HRs with 95% CIs for mortality,according to the Combined associations of TyG and SII, using the low TyG & low SII group as a reference. HR hazard ratio, CI confdence interval, TyG triglyceride–glucose index, SII Systemic Inflammation Index. The event column represents the number of individuals with positive outcomes.
Fig. 4
Fig. 4
Association of TyG and SII with All-Cause and CVD Mortality using RCS. Restricted cubic spline analysis has four knots. In the RCS analysis, adjustments were made for age, sex, ethnicity, marital status, education level, family income, BMI, smoking status, current alcohol consumption, dyslipidemia, hypertension, and CVD. TyG triglyceride–glucose index, SII Systemic Inflammation Index, BMI body mass index, CVD cardiovascular disease. (A) Association of TyG with the risk of mortality; (B) association of SII with the risk of mortality.
Fig. 5
Fig. 5
Predictive performance of the combined TyG and SII for mortality. The receiver operating characteristic (ROC) curve evaluating the discriminative capabilities by calculating the AUC. AUC area under curve, TyG triglyceride–glucose index, SII Systemic Inflammation Index, CVD cardiovascular disease. (A) Combined association with the All-Cause mortality; (B) Combined association with the CVD mortality.
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