The association between novel metabolic parameters and all-cause/cardiovascular mortality in patients with metabolic syndrome is modified by age

Cardiovasc Diabetol. 2025 Feb 28;24(1):96. doi: 10.1186/s12933-025-02587-x.

Abstract

Background: Triglyceride glucose index (TyG) serves as an effective parameter for assessing metabolic status. However, it remains uncertain whether TyG and other metabolic parameters can predict clinical outcomes in people with metabolic syndrome (MetS). We investigated the association of TyG, triglyceride glucose-waist to height ratio (TyG-WHtR), and metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular mortality in the MetS cohort and determined whether this association changes with age.

Method: Participants enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018 were selected and categorized into two groups: younger individuals (age < 65 years) and older individuals (age ≥ 65 years). Three new metabolic indices of TyG, TyG-WHtR, and METS-IR were constructed. The weighted Cox proportional hazards model and restricted cubic spline (RCS) models were employed to evaluate the relation between three indices and mortality outcomes. The time-dependent receiver operating characteristic (ROC) curve assessed the ability of different indices to predict mortality. Sensitivity analysis was conducted to evaluate the robustness and reliability of the findings.

Results: The study comprised a total of 8271 participants, including 5456 younger participants and 2815 older participants, and 1407 deaths were observed over a median follow-up period of 8.3 years. Compared with the first quartile (Q1), the fourth quartile's (Q4) TyG, TyG-WHtR, and METS-IR were linked to an increased risk of all-cause mortality (HR 1.63, 95% CI 1.12-2.39; HR 2.78, 95% CI 1.68-4.61; HR 1.36, 95% CI 1.12-2.02, respectively) and cardiovascular mortality (HR 2.04, 95% CI 1.15-4.90; HR 4.99, 95% CI 1.76-14.11; HR 2.69, 95% CI 1.89-8.15, respectively) in the younger group but not in the older group. The RCS results showed no significant non-linear associations between TyG, TyG-WHtR, METS-IR, and all-cause (P = 0.082; P = 0.712; P = 0.062, respectively) or cardiovascular mortality (P = 0.176; P = 0.793; P = 0.482, respectively) in the older age group. TyG-WHtR demonstrated the highest area under the curve for predicting 3-year mortality in the younger age group, with values of 0.653 for all-cause mortality and 0.688 for cardiovascular mortality.

Conclusion: Our results highlight the predictive value of TyG, TyG-WHtR, and METS-IR in the MetS population, providing new evidence for medical practice and public health.

Keywords: Age; Metabolic syndrome; Mortality; Novel metabolic parameters; Triglyceride glucose index.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers / blood
  • Blood Glucose* / analysis
  • Blood Glucose* / metabolism
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / mortality
  • Cause of Death
  • Female
  • Humans
  • Insulin Resistance*
  • Male
  • Metabolic Syndrome* / blood
  • Metabolic Syndrome* / diagnosis
  • Metabolic Syndrome* / mortality
  • Middle Aged
  • Nutrition Surveys
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Triglycerides* / blood
  • United States / epidemiology

Substances

  • Biomarkers
  • Blood Glucose
  • Triglycerides