Association of triglyceride-glucose (TyG)-Derived inflammatory indices with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: A retrospective cohort study based on NHANES 1999–2018
It is suggested that TyG-derived inflammatory indices may hold clinical value in predicting mortality risk among patients with CKD, and in the first systematic comparison of multiple such indices, TyG-MLR emerged as the best-performing indicator, although its discriminative performance was moderate.
Abstract
Objective The triglyceride-glucose (TyG) index has been explored as a prognostic marker in chronic kidney disease (CKD), but it does not capture the complex interplay of metabolic dysfunction and chronic inflammation inherent to CKD pathogenesis. This study aimed to explore the associations between TyG-derived inflammatory indices and the risks of all-cause and cardiovascular disease (CVD) mortality in patients with CKD. Methods This retrospective cohort study included adults with CKD from the National Health and Nutrition Examination Survey (NHANES) 1999–2018, with mortality follow-up through December 2019. The associations of the TyG index and five TyG-derived inflammatory indices (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI) with mortality risk were evaluated using receiver operating characteristic (ROC) curves and survey-weighted Cox proportional hazards regression models. Results A total of 3,534 patients with CKD were included. TyG-MLR showed the highest area under the ROC curve (AUC) among the evaluated indices, with an AUC of 0.66 for all-cause mortality and 0.68 for CVD mortality. After stratification by TyG-MLR quartiles (Q1–Q4), patients in the Q4 group had an estimated 3.3-year reduction in life expectancy at the age of 45 compared with the Q1 group. Conclusions This study suggests that TyG-derived inflammatory indices may hold clinical value in predicting mortality risk among patients with CKD. In the first systematic comparison of multiple such indices, TyG-MLR emerged as the best-performing indicator, although its discriminative performance was moderate. Prospective validation in independent cohorts is warranted.
Background Cardiovascular disease (CVD) is more common in those with metabolic dysfunction-associated steatotic liver disease (MASLD). Although the triglyceride-glucose index (TyG) and its composite indices are straightforward indicators of insulin resistance, it is yet unknown how they relate to the risk of CVD in the MASLD population. Objectives To explore the correlation of TyG and TyG-waist-to-height ratio (TyG-WHtR) with cardiovascular disease risk in the MASLD population. Design This was a population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2023. Methods Adults with MASLD were included using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). ROC curve assessments, subgroup analyses, smooth curve fitting, and multivariate logistic regression were carried out. Results Among 1,860 participants, TyG (OR=1.27) and TyG-WHtR (OR=1.20) were independently associated with elevated CVD risk after full covariate adjustment (all P<0.05). TyG exhibited a nonlinear association with CVD risk, with an inflection point at 9.28: below this cutoff, higher TyG was strongly linked to greater CVD risk (OR=2.23, 95% CI: 1.56–3.19), whereas no significant association was detected above the threshold. TyG-WHtR also presented a potential inflection point at 5.54. Stratified analyses revealed stronger associations between both indices and CVD among participants without diabetes, and the magnitude of associations varied across racial subgroups. ROC curve analyses indicated that both markers only achieved modest discriminatory performance for identifying prevalent CVD (AUC: 0.606 for TyG; 0.613 for TyG-WHtR). Conclusion TyG and TyG-WHtR showed positive associations with CVD in patients with MASLD, with a remarkable threshold effect observed for TyG. Both indices are simple auxiliary markers to screen high-risk subgroups during population epidemiological surveys.
Song-Shan Li, Shu-Ling Rong, Bin Yang et al.· Therapeutic Advances in Endo...· 0 citations
The observational findings suggest that CTI is associated with long-term all-cause and cardiovascular mortality in MASLD and advanced fibrosis and may help refine early risk stratification in high-risk MASLD populations.
Hao Wang, Yi-Feng Zhou, Xiaoyu Cui et al.· Medicine· 0 citations
Background The triglyceride-glucose (TyG) index and Systemic Inflammatory Response Index (SIRI) are markers of insulin resistance and inflammation, respectively, and are each independently associated with mortality. Their combined prognostic value is not well established. This study aimed to investigate the association between combined categories of TyG and SIRI and cardiovascular (CVD) and all-cause mortality. Methods We included 11,010 participants from the NHANES 1999–2010. All analyses accounted for the complex survey design. We employed Cox models, restricted cubic splines, and time-dependent ROC analyses. The incremental predictive value of the combined categories was assessed using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results A TyG threshold of 8.64 (linear association) and an SIRI threshold of 0.63 (L-shaped association) were identified. Compared to the low-risk group (TyG ≤ 8.64 and SIRI≤0.63), participants with both TyG > 8.64 and SIRI>0.63 had a 68% higher risk of CVD mortality (HR = 1.68, 95% CI: 1.08–2.61, P = 0.021) and a 52% higher risk of all-cause mortality (HR = 1.52, 95% CI: 1.21–1.91, P < 0.0001). Adding the combined categories to a model of traditional risk factors significantly improved reclassification for CVD mortality (NRI = 0.15, P < 0.05). Subgroup and sensitivity analyses supported the robustness of the findings. Conclusions Concurrently high TyG and SIRI identifies individuals at significantly increased mortality risk. This simple, threshold-based stratification may serve as a practical tool for cardiovascular risk assessment.
Yan Liu, Juan Xu, Xiao-Yu Wu et al.· American Heart Journal Plus:...· 0 citations
Background The associations of the triglyceride-glucose (TyG) index and its derived indices with the progression of cardiovascular-kidney-metabolic (CKM) syndrome remain poorly elucidated. Methods We conducted a systematic review and dose-response meta-analysis of 80 observational studies encompassing populations within CKM stages 0–3, evaluating TyG, TyG-BMI, TyG-WC, TyG-WHtR, and CTI for all-cause mortality, cardiovascular disease (CVD) mortality, and CVD incidence (including stroke, coronary heart disease, heart failure and major adverse cardiovascular events). A one-stage mixed-effects approach was used, supplemented by subgroup, meta-regression, leave-one-out, and trim-and-fill analyses. Results In both continuous (per 1-SD increment) and categorical (highest vs. lowest) analyses, TyG-derived indices generally demonstrated stronger risk associations with target outcomes than TyG alone. Notably, CTI, TyG-WC, and TyG-WHtR exhibited higher risk associations. In the highest-category analysis, TyG-WC yielded the most pronounced risk for CVD mortality (RR = 1.52, 95% CI: 1.35–1.70, 95% PI: 1.26–1.82). CTI was associated with a 57% increase in incident CVD (RR = 1.57, 95% CI: 1.33–1.85, 95% PI: 1.00–2.46). Conversely, TyG-BMI showed non-significant associations with mortality-related outcomes (P > 0.05), though it predicted a 51% risk increase for incident CVD (RR = 1.51, 95% CI: 1.36–1.67, 95% PI: 1.05–2.16). Subgroup analysis indicated that these positive associations were pronounced in CKM stages 1–3 but entirely non-significant in stage 0 and the obesity subgroup had a significant impact on the risk of mortality. Dose-response analyses revealed a significant non-linear U-shaped association of the TyG index with all-cause mortality (Pnon-linearity < 0.0001; nadir = 8.90). For CVD mortality, the overall association was significant (Poverall = 0.005; nadir = 8.91), whereas a monotonic increasing trend was observed for CVD incidence (Poverall = 0.0014). In sensitivity analyses excluding participants with cancer or consumptive diseases at baseline, as well as those in CKM stage 0, the U-shaped patterns remained stable (mortality nadir shifted to 9.1). Conclusions TyG-derived indices, particularly TyG-WC, TyG-WHtR, and CTI, show stronger risk associations than the TyG index for cardiovascular risk assessment in CKM populations, whereas the clinical utility of TyG-BMI is relatively limited. Moderate elevations in TyG were associated with lower mortality risk within a certain range, though the non-linear association was confirmed only for all-cause mortality. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251111362, identifier CRD420251111362.
J. An, Xue He, Qian-Ying Hao et al.· Frontiers in Endocrinology· 0 citations
Background/Objectives: Cardiovascular–kidney–metabolic (CKM) syndrome, characterized by disturbances in glucose and lipid metabolism as its core pathophysiological feature, is a major driver of target organ damage. While early risk stratification in CKM stages 0–3 is critical to intercept renal decline, the practical utility of accessible metabolic surrogates remains poorly characterized. This study evaluated and compared the prospective capacity of the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, and C-reactive protein–triglyceride glucose index (CTI) for predicting renal deterioration in early-stage CKM. Methods: Data were extracted from the China Health and Retirement Longitudinal Study (2011–2015). In total, 4064 participants aged ≥ 45 with CKM stages 0–3 (with exclusion of participants with baseline CKM stage 4) were prospectively followed. Renal function decline was defined as an estimated glomerular filtration rate (eGFR) decrease of ≥30% over 4 years, calculated using the CKD-EPI 2012 cystatin C equation. Multivariable logistic regression, restricted cubic splines (RCSs), and receiver operating characteristic (ROC) curves were applied. Results: Overall, 122 participants developed the renal outcome. In fully adjusted models, AIP, TyG, and CTI were valid independent risk factors for renal decline, with the lipid-driven AIP exhibiting the strongest association (OR = 5.54, 95% CI: 3.30–9.29; TyG: OR = 1.97, 95% CI: 1.49–2.59; CTI: OR = 1.63, 95% CI: 1.30–2.05; all p < 0.001). RCS analysis demonstrated significant non-linear dose–response trajectories, with renal risk escalating sharply past specific exploratory inflection points (AIP = 0.97, TyG = 7.80, CTI = 8.07). ROC curves confirmed robust predictive performance (AUCs > 0.75), with AIP performing optimally (AUC = 0.773). Conclusions: AIP, TyG, and CTI are independent longitudinal predictors of renal decline in early-stage CKM, with AIP demonstrating superior discriminatory power. Monitoring these composite indices and maintaining them within observed metabolic ranges may aid in early renal risk stratification and monitoring, though the exploratory statistical inflection points identified require validation in independent cohorts before clinical application.
Shixin Yan, Hai-Yang Liu· Journal of Clinical Medicine· 0 citations
ABSTRACT Background People living with HIV (PWH) are at increased risk for metabolic and cardiovascular diseases. However, there is no structured prevention strategy for these subjects. The triglyceride‐glucose (TyG) index has shown predictive value for Type 2 diabetes mellitus (T2DM) and cardiovascular events (CVEs) in the general population, but its utility in PWH remains unclear. Methods We conducted a retrospective study including 477 PWH without baseline T2DM. TyG index was calculated as follows: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. ROC analysis was used to identify the optimal TyG threshold for T2DM, and logistic regression analysis was used to evaluate the association with T2DM. The association between TyG index and CVEs was investigated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results 477 PWH were included. Median age was 38 years and 26% were women. During a median follow‐up of 14.2 years, 38 participants developed T2DM and 45 experienced CVEs. The TyG index demonstrated fair discrimination for incident T2DM (AUC: 0.675, 95% CI 0.591–0.759), with an optimal threshold of 4.78. Participants with TyG ≥ 4.78 had a higher risk of developing T2DM (aOR 2.86, 95% CI 1.35–6.12). PWH in the highest TyG tertile had also higher risk for CVEs compared with those in the lowest tertile (aHR 3.31, 95% CI 1.10–9.97). Conclusion In PWH, a higher TyG index was independently associated with an increased risk of both T2DM and CVEs over long‐term follow‐up. The TyG index represents a practical, low‐cost tool for early metabolic risk stratification in this population.
Daniele Pastori, G. Gazzaniga, T. Brogi et al.· European Journal of Clinical...· 0 citations
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