Abstract
Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Dysregulation of glucose metabolism and inflammation are key factors in the development of atherosclerosis. The glucose-to-lymphocyte ratio (GLR) is a comprehensive marker for assessing glucose metabolism and inflammation. This study aims to evaluate the association between GLR and all-cause as well as cardiovascular disease (CVD) mortality in patients with ASCVD within the U.S. population. This retrospective cohort study recruited 1,753 ASCVD patients from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) with a median follow-up of 6.25 years. Mortality outcomes were determined by linkage to the National Death Index (NDI) records up to December 31, 2019. Weighted Cox proportional hazard models were used to assess the independent association between GLR and mortality risk. Restricted cubic spline (RCS) curves were used to display the relationship between GLR and all-cause mortality visually, and two-segment Cox proportional hazards models were constructed on either side of the inflection points. Kaplan-Meier survival curves were further used to assess the relationship between GLR and mortality, and further subgroup analyses were performed. Receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive ability of GLR for survival. During a median follow-up of 6.25 years, 624 deaths from various causes were observed, with 254 deaths from CVD. Cox regression analysis revealed a positive association between GLR and both all-cause and CVD mortality. Based on RCS, a J-shaped nonlinear relationship was observed between GLR and all-cause mortality in ASCVD patients, with an inflection point at 3.13. When the GLR < 3.13, it showed a significant negative association with all-cause mortality (HR 0.65, 95% CI 0.47-0.89). When GLR ≥ 3.13 for all-cause mortality, there was a significant positive correlation with all-cause mortality (HR 1.13, 95% CI 1.09-1.17). Subgroup analysis revealed a positive association between GLR and CVD mortality across most subgroups, but the correlation between GLR and CVD mortality was weaker compared to its association with all-cause mortality. In addition, an interaction was detected between GLR and age in relation to all-cause mortality. Moreover, the predictive performance of GLR on all-cause and CVD mortality seemed superior to that of glucose or lymphocytes. Our findings indicate that elevated GLR was closely associated with an increased risk of all-cause mortality and CVD mortality in ASCVD patients. Notably, the relationship between GLR and all-cause mortality exhibited a J-shaped nonlinear pattern, with an inflection point at 3.13.