Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes
Xavier Rossello1, Sergio Raposeiras-Roubin2, Belén Oliva3
1Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; CIBER de Enfermedades CardioVasculares, Madrid, Spain; Cardiology Department, Health Research Institute of the Balearic Islands (IdISBa), Hospital Universitari Son Espases, Palma, Spain. Electronic address: https://twitter.com/RosselloXavier.
Insights
Glycated hemoglobin (HbA1c) levels, even in the nondiabetic range, predict subclinical atherosclerosis (SA) extent. Integrating HbA1c into risk scores can improve identification of individuals at higher risk for SA.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Metabolic Health
Background:
- Protein glycation, measured by glycated hemoglobin (HbA1c), is a metabolic injury not typically included in cardiovascular risk scores.
- Existing risk scores like Systematic Coronary Risk Estimation and atherosclerotic cardiovascular disease risk scales do not account for HbA1c levels.
Purpose of the Study:
- To evaluate the association between HbA1c levels and the extent of subclinical atherosclerosis (SA).
- To determine if HbA1c can enhance the identification of individuals with extensive SA when added to established cardiovascular risk factors (CVRFs).
Main Methods:
- Analysis of a cohort of 3,973 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study.
- Participants had no history of cardiovascular disease and HbA1c within the nondiabetic range.
- Subclinical atherosclerosis (SA) was assessed using 2D vascular ultrasound and noncontrast cardiac computed tomography.
Main Results:
- Adjusted analyses revealed a significant association between HbA1c levels and the multiterritorial extent of SA (p < 0.001).
- This association was significant across all pre-diabetes groups and even below the pre-diabetes threshold (HbA1c 5.5%–5.6%, OR: 1.36).
- Elevated HbA1c increased SA risk in low-risk individuals but not in moderate-risk individuals, modifying risk predictions in most categories.
Conclusions:
- Routine measurement of HbA1c can identify asymptomatic individuals at higher risk for SA beyond traditional CVRFs.
- Consideration of lifestyle interventions and new antidiabetic medications may help lower both HbA1c and SA in non-diabetic individuals.
Background:
The metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale).
Objectives:
The purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs).
Methods:
A cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography.
Results:
After adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335). Relative risk estimations using Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease predictors confirmed that inclusion of HbA1c modified the risk of multiterritorial SA in most risk categories.
Conclusions:
Routine use of HbA1c can identify asymptomatic individuals at higher risk of SA on top of traditional CVRFs. Lifestyle interventions and novel antidiabetic medications might be considered to reduce both HbA1c levels and SA in individuals without diabetes.
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