Associations of stress hyperglycemia ratio with rapid non-culprit lesion progression and clinical outcomes in acute coronary syndrome: a multicenter cohort study according to diabetes status

Background Rapid progression of non-culprit coronary lesions (NCLs) following acute coronary syndrome (ACS) is an important determinant of recurrent cardiovascular events, yet its clinical predictors remain incompletely defined. Stress hyperglycemia ratio (SHR), reflecting acute glycemic elevation relative to chronic glycemic status, has been associated with adverse outcomes in ACS. Its relationship with rapid NCL progression and long-term clinical events according to diabetes status remains unclear. Purpose To assess whether SHR improves risk stratification for rapid NCL progression and subsequent MACE after ACS, and whether its predictive performance differs between patients with and without diabetes. Methods In this multicenter prospective cohort study, consecutive patients with ACS undergoing percutaneous coronary intervention were enrolled. Among 682 patients with serial coronary angiography demonstrating non-culprit lesions, rapid NCL progression was assessed using prespecified criteria. SHR was calculated using fasting blood glucose and glycated hemoglobin (HbA1c). Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, and unplanned revascularization. Multivariable logistic and Cox regression analyses were performed separately in patients with and without diabetes mellitus (DM). Results Rapid NCL progression occurred in 165 patients (24.2%). In patients with DM, higher SHR was independently associated with rapid progression when modeled as both a continuous variable (adjusted odds ratio [OR] 3.28, 95% confidence interval [CI] 1.10–10.22, p=0.035) and a categorical variable (adjusted OR 1.90, 95% CI 1.01–3.57, p=0.046). No significant association was observed in patients without DM. Over a median follow-up of 2.0 years (interquartile range 1.14–2.13), 251 patients (36.8%) experienced MACE. Rapid NCL progression was strongly associated with subsequent MACE in both diabetic and non-diabetic groups. In patients with DM, the combination of rapid progression and elevated SHR was associated with increased risk of MACE (adjusted hazard ratio [HR] 3.12, 95% CI 1.77–5.49, p<0.001). In patients without DM, elevated SHR alone was independently associated with MACE (adjusted HR 1.72, 95% CI 1.12–2.65, p=0.014), and the highest risk was observed in those with both rapid progression and elevated SHR (adjusted HR 5.73, 95% CI 3.46–9.50, p<0.001). Conclusions In this multicenter ACS cohort, rapid progression of non-culprit lesions was strongly associated with adverse cardiovascular outcomes. SHR was independently related to angiographic progression among patients with diabetes and identified higher-risk individuals in both diabetic and non-diabetic populations. These findings emphasize the prognostic relevance of non-culprit lesion dynamics and support further evaluation of stress-related glycemic markers in risk stratification following ACS.