Glycated hemoglobin measurement and prediction of cardiovascular disease
, Emanuele Di Angelantonio1, Pei Gao1
1University of Cambridge, Cambridge, United Kingdom.
Insights
Measuring glycated hemoglobin (HbA1c) offers minimal additional benefit in predicting cardiovascular disease (CVD) risk for individuals without diabetes. This finding suggests current risk factors are largely sufficient for CVD event prediction.
Area of Science:
- Cardiology
- Endocrinology
- Preventive Medicine
Background:
- The predictive value of glycated hemoglobin (HbA1c) for initial cardiovascular events is not well-established.
- Conventional cardiovascular risk factors are used to estimate an individual's risk for cardiovascular disease (CVD).
Purpose of the Study:
- To evaluate if incorporating HbA1c measurements into existing cardiovascular risk assessment models improves the prediction of CVD risk.
- To determine the incremental benefit of HbA1c testing for cardiovascular event prediction.
Main Methods:
- Analysis of individual participant data from 73 prospective studies, encompassing 294,998 participants without prior diabetes or CVD.
- Assessed risk discrimination using C-index and reclassification using net reclassification improvement for 10-year CVD risk categories.
Main Results:
- An approximately J-shaped association was observed between HbA1c levels and CVD risk, with slight changes after adjusting for lipids or kidney function.
- The addition of HbA1c to conventional risk factors resulted in a small increase in the C-index (0.0018) and net reclassification improvement (0.42).
- HbA1c provided similar or better predictive improvement compared to fasting, random, or postload glucose measurements.
Conclusions:
- In individuals without diagnosed CVD or diabetes, measuring HbA1c provides little additional value for predicting future cardiovascular events.
- Current cardiovascular risk assessment models incorporating conventional factors appear largely adequate for risk stratification.
Importance:
The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain.
Objective:
To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk.
Design, Setting, And Participants:
Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment.
Main Outcomes And Measures:
Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk.
Results:
During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels.
Conclusions And Relevance:
In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
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