Insulin resistance metric and risk of all-cause mortality: a comparative population-based study in Portugal

Introduction Atherosclerotic 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. METS-IR assessors for IR are employed in clinical evaluations; however, their relationship with all-cause mortality is poorly understood. Objective To investigate the association between the METS-IR, a marker of Insulin resistance, and all-cause mortality in patients with atherosclerotic cardiovascular disease. Methods A cohort study was conducted with 1,720 cardiovascular patients (78.8% male; mean age 53.3±7.9 years) with cardiometabolic conditions, with an extended follow-up (average 7.6±6.7 years). The IR levels were assessed using a surrogate marker METS-IR=[ln[2xfasting plasma glucose (FPG)+ triglycerides (TG)]x body mass index (BMI)]/ln[HDL-cholesterol (HDL-C)]. To investigate the associations between this marker and all-cause mortality, multivariable Cox proportional hazards models were applied. We employed restricted cubic splines (RCS) to examine non-linear associations. Results Of the 1,720 patients with cardiovascular disease, 550 deaths from all causes were registered during follow-up time. The METS-IR threshold value for all-cause mortality was 49.4. When values exceeded this threshold, it demonstrated a positive correlation with all-cause mortality (HR 1.222; 95% CI: 1.020–1.465; p=0.030), along with age (HR=1.040; p<0.0001), smoking (HR=1.416; p<0.0001) and diabetes (HR=1.256; p=0.012). The RCS graph showed a non-linear association between METS-IR and all-cause mortality, with lower risk at lower METS-IR levels, followed by a gradual increase that becomes pronounced at higher METS-IR levels. Conclusion METS-IR was significantly associated with all-cause mortality, highlighting its value as a prognostic marker for identifying high-risk individuals within cardiometabolic populations. Identifying a threshold METS-IR may serve as a target for preventive interventions reducing the risk of premature death.