Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease

Abstract

Backgrounds: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD.

Methods: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices.

Results: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [_TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; _TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; _TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; _TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; _TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices.

Conclusion: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.

Keywords: All-cause mortality; Cardiovascular mortality; Insulin resistance; MASLD; TyG index; TyG-WC index; TyG-WHtR index.

Fig. 1

Scheme of the aim of the study and participants selection process. We aim to evaluate the association between varied TyG-related indices with the mortality outcomes of adults with MASLD. MASLD, metabolic dysfunction-associated steatotic liver disease; TyG, triglyceride-glucose; WC, waist circumference; WHtR, waist to height ratio; BMI, body mass index; HDL, high-density lipoprotein; TG, triglyceride. *Other potential causes of SLD: viral hepatitis, autoimmune liver disease, genetic liver diseases, drug- or medication-induced liver disease, and alcohol-related liver disease

Fig. 2

Kaplan–Meier curves show the survival patterns of MASLD adults with different quartile levels of TyG-related indices. A–C refers to the all-cause mortality of MASLD adults with different quartile levels of TyG-related indices. D–F refers to the cardiovascular mortality of MASLD adults with different quartile levels of TyG-related indices. TyG, triglyceride–glucose; MASLD, metabolic dysfunction-associated steatotic liver disease; Q, quartile

Fig. 3

Forest plots show the association between TyG-related indices with the all-cause mortality among adults with MASLD. A TyG index; B TyG-WC index; C TyG-WHtR index. MASLD, metabolic dysfunction-associated steatotic liver disease; TyG, triglyceride–glucose; WC, waist circumference; WHtR, waist to height ratio; Q, quartile. Model 1: unadjusted; Model 2: adjusted for age, gender, race; Model 3: adjusted for age, gender, race, marital status, educational level, energy intakes, poverty income ratio, smoking status, alcohol use, CVD, CKD, cancer, AST, ALT, and TC

Fig. 4

Forest plots show the association between TyG-related indices the cardiovascular mortality among adults with MASLD. A TyG index; B TyG-WC index; C TyG-WHtR index. MASLD, metabolic dysfunction-associated steatotic liver disease; TyG, triglyceride–glucose; WC, waist circumference; WHtR, waist to height ratio; Q, quartile. Model 1: unadjusted; Model 2: adjusted for age, gender, race; Model 3: adjusted for age, gender, race, marital status, educational level, energy intakes, poverty income ratio, smoking status, alcohol use, CVD, CKD, cancer, AST, ALT, and TC

Fig. 5

Restricted cubic splines reflect the dose-effect relationships between TyG-related indices with the all-cause mortality among adults with MASLD. A TyG index; B TyG-WC index; C TyG-WHtR index. MASLD, metabolic dysfunction-associated steatotic liver disease; TyG, triglyceride–glucose; WC, waist circumference; WHtR, waist to height ratio

Fig. 6

Restricted cubic splines reflect the dose-effect relationships between TyG-related indices the cardiovascular mortality among adults with MASLD. A TyG index; B TyG-WC index; C TyG-WHtR index. MASLD, metabolic dysfunction-associated steatotic liver disease; TyG, triglyceride–glucose; WC, waist circumference; WHtR, waist to height ratio