Delta-glycated hemoglobin: A novel independent risk factor for cardiovascular events in patients without diabetes mellitus

Background: A single measurement of glycated hemoglobin (HbA1c) is a weak predictor for cardiovascular events in patients without Type 2 diabetes mellitus. We hypothesized that dynamic changes in HbA1c (Delta-HbA1c) would better predict cardiovascular outcome than a single value. Methods: In 99 consecutive patients with stable coronary artery disease (CAD) and without diabetes mellitus who were seen twice in our outpatient clinic (4–6 months apart) in 1998, Delta-HbA1c (follow-up HbA1c–baseline HbA1c) was assessed. Between August and September 2007 (mean observation period 9.1 yr), patients and their physicians were contacted by telephone to evaluate the incidence of cardiovascular endpoints. The combined primary endpoint of our study was defined as the incidence of myocardial infarction, stroke or death from any cause. The endpoints were validated by chart review. Results: Multivariate analysis demonstrated that the change of HbA1c between first and second examination in 1998 was the most powerful parameter for prediction of the combined primary endpoint in the next 9 yr. The hazard ratio was 5.03 [95% confidence interval (CI) 1.4–17.9] for any increase in HbA1c and 1.99 (95%CI 1.3–3.0) for an HbA1c increase of 0.3%. In addition, Kaplan-Meier survival analysis showed a significant association between endpoint-free survival and dynamic changes in HbA1c. Conclusions: Hence, changes in the glucometabolic milieu within 4–6 months calculated by the difference of two values of HbA1c affect the long-term prognosis of patients with CAD but without diabetes mellitus.