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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Prognostic impact of prediabetic glycated hemoglobin levels in nondiabetic patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis
Sufyan Shahid, Furqan Ahmad Sethi, Shahzaib Ahmed, Akash Kumar, Muhammad Hamza Shahid, Hafsa Arshad Azam Raja, Muhammad Usama, Hafiz Muhammad Faizan Mughal
Sufyan Shahid, Muhammad Usama, Hafiz Muhammad Faizan Mughal, Department of Cardiology, Khawaja Muhammad Safdar Medical College, Sialkot 51310, Punjab, Pakistan
Furqan Ahmad Sethi, Department of Medicine, Khyber Medical College, Hayatabad, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
Shahzaib Ahmed, Department of Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore 54610, Punjab, Pakistan
Akash Kumar, Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro 76080, Sindh, Pakistan
Muhammad Hamza Shahid, Department of Medicine, Akhtar Saeed Medical and Dental College, Lahore 54610, Punjab, Pakistan
Hafsa Arshad Azam Raja, Department of Medicine, Rawalpindi Medical University, Rawalpindi 46000, Punjab, Pakistan
Author contributions: Shahid S designed research, conceptualization, methodology, data curation, analyzed data, and wrote the paper; Sethi FA performed research, contributed analytic tools, analyzed data, and wrote the paper; Ahmed S performed research, contributed analytic tools, analyzed data, and wrote the paper; Kumar A performed research, analyzed data, and wrote the paper; Shahid MH performed quality assessment of included studies, and wrote the paper; Raja HAA contributed data curation, performed quality assessment and writing-review and editing; Usama M supervised and contributed to writing-review and editing; Mughal HMF supervised and contributed to writing-review and editing.
Conflict-of-interest statement: The authors have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Sufyan Shahid, MBBS, Post Doctoral Researcher, Department of Cardiology, Khawaja Muhammad Safdar Medical College, Islamia College Road, Sialkot 51300, Punjab, Pakistan.
sufyanshahid09@gmail.com
Received: June 10, 2025
Revised: July 13, 2025
Accepted: October 13, 2025
Published online: November 26, 2025
Processing time: 165 Days and 20.9 Hours
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.
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.
