Early relative glycemic stress trajectories identify a high-risk metabolic phenotype in critically ill patients with atherosclerotic cardiovascular disease: a dual-cohort study

Background: The stress hyperglycemia ratio (SHR) captures acute glucose elevation relative to chronic glycemic background. However, the prognostic value of early dynamic SHR patterns in critically ill patients with atherosclerotic cardiovascular disease (ASCVD) remains uncertain. Methods: We conducted a retrospective dual-cohort study using MIMIC-IV v3.1 for trajectory development and NWICU v0.1.0 for external validation. Adults with ASCVD, available HbA1c measurements, and valid SHR values in at least three of six 12-hour windows during the first 72 hours after ICU admission were included. Trajectories were derived in MIMIC-IV using group-based trajectory modeling, and NWICU patients were assigned to the closest MIMIC-IV-derived trajectory. The primary outcome was 28-day all-cause mortality. Cox models adjusted for demographic characteristics, ICU type, comorbidities, severity and functional scores, vital signs, laboratory measurements, and early interventions. Sensitivity, subgroup, and exploratory machine-learning analyses were also performed. Results: The study included 8,835 patients from MIMIC-IV and 1,705 from NWICU. Three early SHR trajectories were identified: moderate-stable, low-declining, and persistently high. The persistently high trajectory was the largest class in both cohorts and showed the poorest 28-day survival. In MIMIC-IV, the fully adjusted hazard ratio for Class 3 versus Class 1 was 1.37 (95% CI 1.15-1.64). The association was also observed in NWICU (HR 2.04, 95% CI 1.39-3.01). Findings for ICU and in-hospital mortality were directionally concordant. HbA1c and first-12-hour maximum glucose were the leading predictors of persistently high trajectory membership. Conclusions: Early SHR trajectories identified a common high-risk metabolic phenotype in critically ill patients with ASCVD. The persistently high trajectory reflected acute glycemic deviation from the HbA1c-defined background and was independently associated with short-term mortality. Dynamic SHR profiling may support metabolic risk stratification in cardiovascular critical illness.