Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

Abstract

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.

CD247, a Novel T Cell–Derived Diagnostic and Prognostic Biomarker for Detecting Disease Progression and Severity in Patients With Type 2 Diabetes

“…Currently, commonly used biomarkers for disease progression and outcome, such as A1C, assess the glycemic exposure but reveal little as to the actual pathologic inflammatory process underlying the progression of microand macrovascular complications (16). This has been recently highlighted by evidence from megatrials such as ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), suggesting a dissociation between changes in A1C upon implementation of intensive antihyperglycemic therapy and progression of macrovascular outcomes (17,18).…”

“…This has been recently highlighted by evidence from megatrials such as ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), suggesting a dissociation between changes in A1C upon implementation of intensive antihyperglycemic therapy and progression of macrovascular outcomes (17,18). Likewise, a recent study showed that assessment of A1C values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk (16).…”

“…Currently, the widely used biomarkers for disease severity and progression in diabetes rely on metabolic parameters and are limited in their ability to improve risk stratification with regards to disease-related outcomes (16). Identifying a more mechanistically relevant biomarker that is linked not only to the metabolic processes but also to the underlying inflammatory process may provide an invaluable clinical tool to predict disease progression and effectiveness of therapeutic interventions.…”

Classical and emergent cardiovascular disease risk factors in type 2 diabetics from the Vallecas area (DICARIVA study)

“…The prevalence of T2DM patients with HbA1c ≥ 6.5% was 85%, suggesting a bad diabetes control and increased CVD risk (4,25) in a very high percentage of volunteers. HbA1c is considered a better indicator of future CVD event than fasting glycemia (25).…”

“…In Spain 30% of mortality is due to CVD (2), being DM considered as an independent CVD risk factor (3). A recent study estimated that for every point increase in glycated haemoglobin (HbA1c), the relative risk of CVD increases by 18% (4).…”