Abstract / Summary
Abstract Background Coronary Heart Disease (CHD) is a leading cause of death among adults, incurring high socio-economic burdens. Prediabetes is highly prevalent in patients with CHD and may be associated with an increased risk of major adverse cardiovascular events (MACE). This study aims to systematically evaluate the effects of prediabetes on the risk of MACE in patients with established CHD and to explore variations in this association across different prediabetes diagnostic criteria. Methods Six bibliographic databases (Embase, PubMed, Web of Science, CNKI, Wanfang Data, and VIP Chinese Journals Database) were systematically searched to 1 January 2026 for prospective and retrospective cohort studies investigating the association between prediabetes (defined by the ADA, WHO or IEC criteria) and MACE in adult patients with CHD. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The risk of bias was assessed by ROBINS-E tool. Subgroup and sensitivity analyses were conducted to explore potential sources of statistical heterogeneity. Results Twenty cohort studies involving a total of 63,425 patients with a median of 3 years follow-up were included. Compared with normoglycemic group, coexisting prediabetes was significantly associated with higher risk of MACE in patients with CHD (pooled HR = 1.22, 95% Cl = 1.12–1.33, I 2 = 44.0%). Consistently, elevated risks were observed for all-cause death: HR = 1.30 (95% CI: 1.12–1.50, I 2 = 0.0%) and cardiac death: HR = 1.24 (95% CI: 1.08–1.42, I 2 = 1.4%). Subgroup analysis by prediabetes diagnostic criteria showed consistent risk elevation across ADA, WHO, and IEC criteria, and suggested that these criteria contributed to the observed statistical heterogeneity. The pooled HRs of glycated hemoglobin (HbA1c) were: ADA-HbA1c: HR = 1.28 (95% Cl: 1.17–1.41, I 2 = 0.0%); IEC-HbA1c: HR = 1.41 (95% Cl: 1.21–1.65, I 2 = 0.0%). The ADA composite criteria (HbA1c + FPG): HR = 1.19 (95% Cl: 1.07–1.33, I 2 = 51.0%); WHO and IEC composite criteria (WHO-FPG, IEC-HbA1c): HR = 1.53 (95% Cl: 1.26–1.85, I 2 = 0.0%). No statistical differences ( P > 0.05) were found across a range of population and study characteristics. Conclusions This meta-analysis of cohort evidence indicates that prediabetes is associated with an increased risk of MACE in patients with coronary heart disease, and the magnitude of risk differs by prediabetes diagnostic criteria. However, pooled estimates for 2h-OGTT were unavailable due to insufficient data. Future studies with more diverse CHD populations and complete outcome reporting are needed to confirm these findings.