The Association Between Different A1C-Based Measures of Glycemia and Risk of Cardiovascular Disease Hospitalization

OBJECTIVE: We tested whether average monthly glycemic burden (AMGB), a marker of hyperglycemia that is a function of the extent and duration that A1C exceeded 7%, indicated greater risk of cardiovascular disease (CVD) than traditional A1C measures. RESEARCH DESIGN AND METHODS: Using a case-control design, we studied 2,456 members of Kaiser Permanente Northwest with type 2 diabetes: 1,228 who experienced a CVD hospitalization, matched on age, sex, and duration of diabetes to 1,228 patients who were not hospitalized for CVD. We calculated AMGB from diabetes diagnosis until CVD hospitalization as a function of the difference between each actual or interpolated A1C measurement and 7%, resulting in an area under the curve estimate of hyperglycemic exposure, adjusted for number of months of observation. We used conditional logistic regression to compare the association between several A1C-based measures of glycemia and CVD, controlling for clinical characteristics and comorbidities. RESULTS: AMGB was associated with increased CVD risk of 29% (odds ratio 1.29 [95% CI 1.16–1.44]; P < 0.001), while mean A1C was associated with a 22% risk increase (1.22 [1.09–1.37]; P < 0.001). A1C ever exceeding 7% was associated with increased CVD risk of 39% (1.39 [1.08–1.79]; P = 0.010). No model with a glycemia measure provided substantially more information than an identical model without a glycemia measure. CONCLUSIONS: AMGB demonstrated somewhat greater CVD risk than mean A1C, but its clinical usefulness may be limited. A1C ever rising above 7% (53 mmol/mol) was a simple predictor of CVD risk that may have important clinical ramifications for newly diagnosed patients.