Hemoglobin A1c and Cardiovascular Risk

Where Are We and How Did We Get Here?

Gregory A. Nichols, PhD


June 24, 2014

In This Article

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, et al
JAMA. 2014;311:1225-1233

Is There Value in Measuring A1c Levels for Cardiovascular Risk Prediction?

In the meta-analysis, the Emerging Risk Factors Collaboration (ERFC) combined individual participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes or cardiovascular disease (CVD) to determine whether adding information on glycated hemoglobin (A1c) values to conventional cardiovascular risk factors was associated with better prediction of CVD risk. A1c measurements were categorized into 0.5% increments from < 4.5% to ≥ 6.5%, and the primary outcome was first CVD event, defined as fatal or nonfatal coronary heart disease or stroke. The authors developed CVD risk prediction models containing conventional risk factors (age, sex, smoking status, systolic blood pressure, and total and high-density lipoprotein cholesterol) without or with A1c, and they calculated improvements in predictive ability using measures of risk discrimination and reclassification.

A Relationship, But Little Predictive Benefit

The mean age of study participants was 58 years, 49% were women, and the median follow-up was 10 years. An approximately J-shaped association was found between A1c and CVD risk (approximate 20% increased risk at < 4.5% and beginning at ≥5.5%, relative to the reference category of 5.0%-5.5%). Small improvements in discrimination were seen when adding A1c to predictive models, but there was no significant improvement in net reclassification.

It is important to note that this study focused on A1c levels that were mostly in the normal range and measured in participants without diabetes or CVD. The study did not account for development of diabetes over follow-up. Furthermore, at a mean age of 58 years, participants were past the point at which 65% of diabetes cases are diagnosed.[1]



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