Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Study Questions:

What is the value of adding information on glycated hemoglobin (HbA1c) to conventional cardiovascular risk factors in the prediction of first-onset cardiovascular disease (CVD) outcomes in middle-aged and older adults without a known history of diabetes mellitus?


This was an analysis of data from 294,998 participants (from 73 prospective cohorts and 20 countries) without a known history of diabetes or CVD at baseline. Studies were included if, among other criteria, they had assayed HbA1c, or fasting, random, or postload glucose level. The primary outcome was first-onset CVD, defined as fatal or nonfatal coronary heart disease event or any stroke. The authors developed CVD risk prediction models containing several conventional risk factors with or without a glycemia measure. Improvement in predictive ability was assessed with measures of risk discrimination (i.e., C-index) and reclassification (i.e., net reclassification improvement) across 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥7.5%) risk.


A total of 20,840 incident fatal and nonfatal CVD outcomes were recorded during a median follow-up of 9.9 years. There was a J-shaped association between each glycemia measure studied and CVD risk. The addition of HbA1c was associated with a marginal change in C-index of 0.0018 (0.0003-0.0033). The addition of information on glycemia measures did not yield significant improvement in net reclassification.


The assessment of HbA1c in individuals without known CVD or diabetes provides little incremental benefit to prediction of first-onset CVD.


This is an important study that establishes the use of HbA1c (or another measure of glycemia) is not associated with a clinically meaningful difference in assessment of risk for first-onset CVD. Such findings support the 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk, which does not recommend a measurement of glycemic index for the purposes of risk assessment. Less is more.

Keywords: Hemoglobin A, Glycosylated, Stroke, Follow-Up Studies, Blood Glucose, Middle Aged, Cardiovascular Diseases, Coronary Disease, Glycemic Index, Risk Assessment, Diabetes Mellitus

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