The combined and mediating prognostic impact of inflammation and stress hyperglycemia in diabetic and nondiabetic patients with acute coronary syndrome

Background and aims The interaction between stress hyperglycemia and inflammation in patients with acute coronary syndrome (ACS) and its potential variation between diabetic and non-diabetic patients remains unclear. This study aims to investigate the combined and mediating effects of the stress hyperglycemia ratio (SHR) and high-sensitivity C-reactive protein (hsCRP) on mortality risk in diabetic and non-diabetic ACS patients. Methods Data from 6,425 ACS patients, including 3,677 with diabetes and 2,748 without, were analyzed from a large multicenter nationwide cohort. SHR was calculated as admission glucose (mmol/L) / [1.59 × HbA1c (%) − 2.59]. The primary endpoint was all-cause mortality. Results Among 6,425 ACS patients, we found that both elevated SHR and hsCRP levels were independently associated with higher mortality risks, regardless of diabetic status. Patients with both high SHR (>1.08) and high hsCRP (>4.24 mg/L) levels had the greatest all-cause mortality risk in both diabetic (HR 2.50, 95% CI 1.45-4.31) and non-diabetic groups (HR 2.33, 95% CI 1.39-3.93). However, a significant interaction effect between hsCRP and SHR for all-cause mortality risk was only observed in non-diabetic ACS patients (P=0.010), but not in diabetic individuals (P=0.376). HsCRP mediated 12.3% of the association between SHR and mortality in non-diabetic patients, compared to 3.6% in diabetic patients after full covariate adjustment. Conclusion Elevated SHR and hsCRP levels are strong predictors of mortality in ACS patients, with the interaction and mediating effects of hsCRP being more pronounced in non-diabetic patients. These findings underscore the importance of tailored risk stratification strategies based on stress hyperglycemia and inflammation profiles in diabetic and non-diabetic ACS patients.