Interpreting Hemoglobin A1C in Combination With Conventional Risk Factors for Prediction of Cardiovascular Risk

BACKGROUND: Hemoglobin A1C (HbA1C) is associated with increased risk of cardiovascular events, but its use for prediction of cardiovascular disease (CVD) events in combination with conventional risk factors has not been well defined. METHODS AND RESULTS: To understand the effect of HbA1C on CVD risk in the context of other CVD risk factors, we analyzed HbA1C and other CVD risk factor measurements in 2000 individuals aged 40 to 79 years without pre-existing diabetes mellitus or CVD from the 2011 to 2012 National Health and Nutrition Examination Surveys survey. The resulting regression model was used to predict the HbA1C distribution based on individual patient characteristics. We then calculated post-test 10-year atherosclerotic CVD risk incorporating the actual versus predicted HbA1C, according to established methods, for a set of example scenarios. Age, sex, race/ethnicity, and traditional cardiovascular risk factors were significant predictors of HbA1C in our model, with the expected HbA1C distribution being significantly higher in non-Hispanic black, non-Hispanic Asian, and Hispanic individuals than that in non-Hispanic white/other individuals. Incorporating the expected HbA1C distribution into pretest atherosclerotic CVD risk has a modest effect on post-test atherosclerotic CVD risk. In the patient examples, we assessed that having an HbA1C of <5.7% reduced post-test risk by 0.4% to 2.0% points, whereas having an HbA1C of ≥6.5% increased post-test risk by 1.0% to 2.5% points, depending on the scenario. The post-test risk increase from having an HbA1C of ≥6.5% tends to approximate the risk increase from being 5 years older. CONCLUSIONS: HbA1C has modest effects on predicted atherosclerotic CVD risk when considered in the context of conventional risk factors.