Adjustment of the GRACE score by HemoglobinA1c enables a more accurate prediction of long-term major adverse cardiac events in acute coronary syndrome without diabetes undergoing percutaneous coronary intervention

Background: The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome (ACS). Chronic hyperglycemia [hemoglobinA1c (HbA1c)] can independently predict major adverse cardiac events (MACEs) in patients with ACS. We investigated whether the prediction of MACEs with the GRACE score could be improved with the addition of HbA1c content in ACS patients without diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI). Methods: We enrolled 549 ACS patients without DM who underwent PCI. The GRACE score and HbA1c content were determined on admission. Correlation was analyzed by Spearman's rank correlation. Cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the predictive value of HbA1c content alone and combined with GRACE score was estimated by the area under the receiver-operating characteristic curve (AUC), continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: During a median of 42.3 months (interquartile range 39.3-44.2 months), 16 (2.9 %) were lost to follow-up, and patients experienced 69 (12.9 %) MACEs: 51 (9.6 %) all-cause deaths and 18 (3.4 %) nonfatal myocardial infarction cases. The GRACE score was positively associated with HbA1c content. Multivariate Cox analysis showed that both GRACE score and HbA1c content were independent predictors of MACEs (hazard ratio 1.030; 95 % CI 1.020-1.040; p < 0.001; 3.530; 95 % CI 1.927-6.466; p < 0.001, respectively). Furthermore, Kaplan-Meier analysis demonstrated increased risk of MACEs with increasing HbA1c content (log-rank 33.906, p < 0.001). Adjustment of the GRACE risk estimate by HbA1c improved the predictive value of the GRACE score [increase in AUC from 0.75 for the GRACE score to 0.80 for the GRACE score plus HbA1c, p = 0.012; IDI = 0.055, p < 0.001; NRI (> 0) = 0.70, p < 0.001]. Conclusions: HbA1c content is positively associated with GRACE risk score and their combination further improved the risk stratification for ACS patients without DM undergoing PCI.