Nonlinear association of TyG index and METS-IR with cardiovascular mortality in cardiometabolic patients: a long-term cohort study
G Abreu, M Mendonca, M Ferreira, F Sousa, F Escorcio Silva, E Henriques, S Freitas, M Rodrigues, S Borges, A Cardoso, I Ornelas, A Drumond, A C Sousa, R Palma dos ReisAbstract
Introduction
Cardiovascular diseases with cardiometabolic conditions have a high prevalence of comorbidities and an elevated mortality risk. Insulin resistance (IR) is a significant contributor to their pathogenesis. Several assessors for IR are employed in clinical evaluations; however, their relationship with mortality is imprecise.
Objective
This study aimed to investigate the association between various markers of IR and cardiovascular (CV) mortality in patients with cardiometabolic diseases.
Methods
This cohort study included 1,720 cardiovascular patients with cardiometabolic conditions (78.8% male; mean age, 53.3±7.9 years) with extended follow-up (average, 7.6±6.7 years). The IR levels were assessed using four surrogate markers, such as: triglyceride-glucose (TyG) index, TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), and metabolic score for insulin resistance (METS-IR)=[ln(2xfasting plasma glucose +triglycerides)xBMI]/ln(HDL-C). To investigate the associations between different IR surrogates and both all-cause and CV mortalities, Cox proportional hazard models were applied. We employed restricted cubic splines (RCS) to examine nonlinear associations.
Results
Among 1,720 patients, 361 (21.0%) died from CV causes. In bivariate analysis, the four surrogate markers were significantly correlated with CV mortality (all with p<0.0001). However, Cox regression analyses of the four surrogate markers showed that only the TyG index and METS-IR were significantly and independently associated with CV mortality. The optimal threshold values for CV mortality for TyG and METS-IR were 9.3 and 48.9, respectively. Above their respective inflexion points, both markers demonstrated a positive correlation with CV mortality (HR 1.27; 95%CI: 1.01–1.61; p=0.044 and HR=1.29; 95%CI: 1.04-1.61; p=0.023, respectively). RCS analysis revealed a nonlinear relationship for both TyG and METS-IR, and CV mortality, with little risk change in at low–moderate TyG levels but a steep, progressive increase in risk at higher TyG and METS-IR values. Overall, elevated TyG and METS-IR are associated with substantially higher CV mortality.
Conclusion
TyG index and METS-IR are significantly associated with CV mortality. This study highlights the prognostic significance of these two markers, particularly in predicting CV mortality, helping guide early intervention strategies (lifestyle changes and therapeutic interventions).Surrogate index