Abstract
BACKGROUND: Glycated hemoglobin (HbA1c) is a well-established biomarker for diagnosing and managing diabetes. However, its prognostic significance in patients without diagnosed diabetes undergoing percutaneous coronary intervention (PCI) remains uncertain. This systematic review and meta-analysis evaluates the association between elevated HbA1c levels in the prediabetic range (≥ 5.7%) and adverse cardiovascular outcomes in this population. AIM: To investigate the association between elevated HbA1c levels in the prediabetic range and adverse outcomes in patients without diagnosed diabetes undergoing PCI. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Central through April 2025 for studies comparing clinical outcomes in coronary artery disease (CAD) patients without a prior diabetes diagnosis, stratified by HbA1c levels (≥ 5.7% vs < 5.7%). Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model. Statistical analysis was performed using R software (version 4.3.2). Primary outcomes were long-term all-cause mortality and major adverse cardiovascular events (MACE); secondary outcomes included short-term mortality and cardiac death. RESULTS: Ten studies involving 32403 patients (mean age: 60 years; 29% female) were included. Elevated HbA1c levels in patients without diagnosed diabetes were significantly associated with increased risk of long-term all-cause mortality (RR: 1.30; 95%CI: 1.10-1.54; P < 0.01; I (2) = 41%) and MACEs (RR: 1.31; 95%CI: 1.01-1.69; P = 0.04; I (2) = 61%). Although the risks of short-term all-cause mortality (RR: 1.16; 95%CI: 0.88-1.53; P = 0.29; I (2) = 1%) and cardiac mortality (RR: 1.76; 95%CI: 0.85-3.67; P = 0.13; I (2) = 94%) were elevated, they did not reach statistical significance. Sensitivity analyses confirmed the robustness of the findings despite moderate to high heterogeneity in some outcomes. CONCLUSION: Among CAD patients without diagnosed diabetes, elevated HbA1c levels in the prediabetic range (≥ 5.7%) are independently associated with worse long-term outcomes following PCI. HbA1c may serve as a valuable biomarker for post-PCI risk stratification in this metabolically at-risk group.