Hemoglobin Glycation Index and Prognosis in Patients with Acute Myocardial Infarction Without Reduced Left Ventricular Ejection Fraction: A Multicenter Retrospective Cohort Study

ABSTRACT Background The prognostic value of the hemoglobin glycation index (HGI) in patients with acute myocardial infarction (AMI) without reduced left ventricular ejection fraction (LVEF) remains unclear. Methods This multicenter retrospective cohort study included 1706 patients with AMI without reduced LVEF. HGI was calculated as measured HbA1c minus predicted HbA1c. Restricted cubic spline (RCS) analysis was used to evaluate nonlinear associations between HGI and outcomes and identify the cutoff value. Piecewise Cox regression and subgroup analyses were also performed. The primary endpoint was major adverse cardiovascular events (MACEs), defined as a composite of rehospitalization for heart failure (HF), recurrent myocardial infarction (MI), and cardiovascular death. Results The median follow‐up was 3.86 (2.30–4.98) years. RCS analysis showed a non‐linear association between HGI and adverse outcomes, with a cutoff at −0.174. In patients with HGI ≤ −0.174, higher HGI was associated with lower risks of rehospitalization for HF (HR = 0.600, 95% CI: 0.464–0.776), recurrent MI (HR = 0.599, 95% CI: 0.365–0.983), cardiovascular death (HR = 0.627, 95% CI: 0.458–0.859), all‐cause death (HR = 0.552, 95% CI: 0.428–0.713), and MACEs (HR = 0.603, 95% CI: 0.483–0.753) after multivariable adjustment. In contrast, no significant associations were observed in patients with HGI > −0.174 after adjustment. Within the lower‐HGI subgroup, severely low HGI was associated with a higher risk of rehospitalization for HF and MACEs compared with mildly low HGI. Subgroup analyses were generally consistent with the main results. Conclusions In AMI patients without reduced LVEF, HGI showed a non‐linear association with adverse outcomes, mainly in the lower‐HGI range. These exploratory findings require prospective validation before clinical application. Trial Registration: ClinicalTrials.gov Identifier: NCT04485988 and NCT04564365