Prognostic impact of prediabetic glycated hemoglobin levels in nondiabetic patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis

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; I² = 41%) and MACEs (RR: 1.31; 95%CI: 1.01-1.69; P = 0.04; I² = 61%). Although the risks of short-term all-cause mortality (RR: 1.16; 95%CI: 0.88-1.53; P = 0.29; I² = 1%) and cardiac mortality (RR: 1.76; 95%CI: 0.85-3.67; P = 0.13; I² = 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.

Keywords: Glycated hemoglobin; Percutaneous coronary intervention; Coronary artery disease; Non-diabetic patients; Major adverse cardiovascular events

Core Tip: Patients without a formal diabetes diagnosis may still exhibit elevated glycated hemoglobin (HbA1c) levels in the prediabetic range (5.7%-6.4%), which may contribute to worse cardiovascular outcomes. This systematic review and meta-analysis examined the prognostic impact of elevated HbA1c in non-diabetic patients undergoing percutaneous coronary intervention (PCI). We found that HbA1c ≥ 5.7% is independently associated with increased long-term all-cause mortality and major adverse cardiovascular events. These findings highlight the potential value of HbA1c as a simple, cost-effective marker for post-PCI risk stratification and emphasize the need for early intervention in this high-risk group.