Abstract
BACKGROUND: To evaluate the independent and combined effects of mean blood glucose (MBG) and glycemic variability (GV) on 28-day mortality in older adults with acute myocardial infarction (AMI). METHODS: A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, focusing on AMI patients aged ≥ 65 years. Participants were stratified into age cohorts: 65–75, 75–85, and ≥ 85 years. MBG and GV were derived from all glucose readings throughout the ICU stay. The primary outcome was 28-day mortality, and hypoglycemia was a secondary outcome. Cox regression with risk-adjusted restricted cubic splines was applied to examine associations. RESULTS: Among 1,242 older adults (mean age 77.3 ± 7.5 years), the mean MBG was 147.1 ± 43.1 mg/dL and median GV was 33.5 (IQR 20.7–55.0) mg/dL. During follow-up, 295 participants (23.8%) died within 28 days. Multivariable analysis showed that each 10 mg/dL increase in MBG and GV was linked to a 17% (Model 3: HR = 1.17; 95% CI, 1.13–1.20) and 6% (HR = 1.06; 95% CI, 1.03–1.08) higher mortality risk, respectively (both p < 0.001). Further analysis, using the low MBG/low GV group as the reference, revealed distinct mortality risk patterns. The high MBG/low GV subgroup exhibited the strongest association with mortality, showing a 5.77-fold increased risk (HR = 5.77; 95% CI, 3.36–9.92; p < 0.001). These associations remained consistent in both diabetic and non-diabetic subgroups (p < 0.001). CONCLUSIONS: Elevated mean blood glucose and glycemic variability independently predicted 28-day mortality in older adults with acute myocardial infarction. Critically, sustained hyperglycemia demonstrated greater clinical detriment than acute glucose fluctuations, necessitating risk-stratified glycemic protocols prioritizing MBG control in this vulnerable population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-025-06499-z.