Clinics (Sao Paulo). 2026 Sep 6;81:101089. doi: 10.1016/j.clinsp.2026.101089. Online ahead of print.
ABSTRACT
BACKGROUND AND PURPOSE: While Triglyceride-Glucose (TyG) index links to Cardiovascular and Cerebrovascular Diseases (CVDs), prior studies neglected competing risks and direct comparisons with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). We evaluated and compared their associations with CVDs mortality under competing risks among non-diabetic adults aged ≥ 45-years.
METHODS: Using NHANES data (2003‒2020), we analyzed 8735 non-diabetic participants. TyG and HOMA-IR were calculated for each participant. Mortality outcomes included all-cause, CVDs, cardiac and cerebrovascular disease. We used Cox proportional hazards regression with C-statistic comparison, along with restricted cubic splines to examine nonlinear associations. To address competing risks, Fine‑Gray models were used to evaluate cause‑specific mortality, followed by a sensitivity analysis excluding participants with baseline CVDs.
RESULTS: Among 1,804 total deaths (599 CVDs), an elevated TyG index showed linear positive associations with risks of all-cause mortality (Model 3, adjusted Hazard Ratios [HR = 1.19], p = 0.005), CVDs mortality (HR = 1.31, p = 0.02), and cerebrovascular mortality (HR = 1.92, p < 0.001). For HOMA-IR, continuous-variable analysis revealed significant linear associations with several mortality outcomes, whereas tertile and RCS analyses suggested more complex, nonlinear relationships. C-statistic comparisons showed no significant improvement in predictive discrimination with either index beyond traditional risk factors. However, in competing risk models, higher TyG remained associated with increased CVDs mortality, while HOMA-IR was associated with a lower subdistribution hazard.
CONCLUSION: Among non-diabetic older adults, the TyG index demonstrated a linear association with CVDs mortality, while HOMA-IR showed a more complex J-shaped pattern. Future research could explore interventions targeting the TyG index to potentially improve survival in the elderly.
PMID:42702103 | DOI:10.1016/j.clinsp.2026.101089