Life's essential 8 metrics and mortality outcomes in insulin resistance: The role of inflammation, vascular aging, and gender

Background Insulin resistance (IR) elevates cardiovascular disease (CVD) and mortality risks. Insulin resistance (IR) increases the risk of cardiovascular diseases (CVD) and mortality. Recently, the American Heart Association introduced the Life's Essential 8 (LE8) framework to assess cardiovascular health (CVH). However, its impact on mortality in IR populations is unknown. Methods Analyzing 2005-2018 National Health and Nutrition Examination Survey data, we studied 5,301 IR adults (≥20 years). LE8 scores were calculated and participants were categorized into low, moderate, and high CVH groups. Systemic immune-inflammation index (SII) and heart age/vascular age (HVA) were measured as potential mediators. Cox models estimated all-cause and CVD mortality hazard ratios (HRs), stratified by LE8 score and sex, and adjusted for covariates. Mediation analyses assessed SII and HVA's indirect effects. This study is an observational cohort study. Results Over a 7.5-year median follow-up, 625 deaths occurred, including 159 CVD-related. Compared to low CVH, moderate and high CVH groups showed reduced all-cause (HR=0.72, 95% CI 0.58-0.89; HR=0.38, 95% CI 0.22-0.67) and CVD mortality (HR=0.42, 95% CI 0.26-0.69; HR=0.15, 95% CI 0.04-0.57). A 10-point LE8 increase correlated with 15% and 31% reductions in all-cause and CVD mortality, respectively. SII and HVA mediated up to 38% and 12% of these effects. The LE8's protective effect was more pronounced in men. Conclusion LE8 effectively evaluates CVH and lowers mortality risk in IR adults, partially mediated by SII and HVA. The findings inform clinical practice and public health strategies for CVD prevention in IR populations.