The combined effect of visit-to-visit variability in HbA1c and systolic blood pressure on the incidence of cardiovascular events in patients with type 2 diabetes

Objective: To investigate the association between long-term visit-to-visit variability in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) and the incidence of cardiovascular disease (CVD) in patients with type 2 diabetes. Methods: We retrospectively enrolled 632 patients with type 2 diabetes and no history of CVD who first visited our hospital between 1995 and 1996, were followed-up for >= 1 year, attended at least 4 clinic visits and had at least 1 visit per year. Patients were followed until June 2012 at the latest, and mailed questionnaires. Results: During the median follow-up period (15.4 years), 81 patients developed CVD. Multivariate analysis revealed that the coefficient of variation (CV) and the variation independent of mean (VIM) for HbA1c and SBP were significant predictors of CVD incidence independent of mean HbA1c and SBP. Patients were classified into 4 groups by median HbA1cCV and SBPCV values and by median HbA1cVIM and SBPVIM values. Among these groups, the HRs were highest in the high-HbA1cCV/high-SBPCV and high-HbA1cVIM/high-SBPVIM groups and were significantly higher compared with those in the low-HbA1cCV/low-SBPCV and low-HbA1cVIM/low-SBPVIM groups, respectively. Among patients with mean SBP >= 130 mm Hg, the HRs associated with HbA1cCV and HbA1cVIM were drastically elevated compared with those with mean SBP<130 mm Hg ( interaction p<0.05). Conclusions: Long-term visit-to-visit variability in HbA1c and SBP represented a combined and additive risk for CVD incidence in patients with type 2 diabetes. It is suggested that a synergistic effect exists between HbA1c variability and mean SBP levels for CVD incidence.