Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2021 Jun 8;77(22):2777-2791.
doi: 10.1016/j.jacc.2021.03.335.

Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes

Xavier Rossello  1 , Sergio Raposeiras-Roubin  2 , Belén Oliva  3 , Fátima Sánchez-Cabo  3 , José M García-Ruíz  4 , Francisca Caimari  5 , José M Mendiguren  6 , Enrique Lara-Pezzi  4 , Héctor Bueno  7 , Leticia Fernández-Friera  8 , Antonio Fernández-Ortiz  9 , Javier Sanz  10 , Borja Ibanez  11 , Valentin Fuster  12
Affiliations
Free article
Observational Study

Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes

Xavier Rossello et al. J Am Coll Cardiol. .
Free article

Abstract

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.

Keywords: diabetes; glycated hemoglobin (HbA1c); pre-diabetes; subclinical atherosclerosis.

PubMed Disclaimer

Conflict of interest statement

Funding Support and Author Disclosures The PESA study is funded by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Banco Santander. The study also receives funding from the Instituto de Salud Carlos III (ISCIII, PI15/02019, PI17/00590, and PI20/00819) and the European Regional Development Fund (ERDF) “A way to make Europe.” The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation. Dr. Bueno has received grants from the Instituto de Salud Carlos III; has received consultancy fees from Bayer, Novartis, Ferrer, MEDSCAPE-the Heart-org, and Janssen; has received grants, consultancy fees, and nonfinancial support from AstraZeneca; and has received grants and consultancy fees from Bristol Myers Squibb-Pfizer, all unrelated to the present study. Dr. Ibanez is supported by the European Commission (ERC-CoG grant Nº 819775), the Spanish Ministry of Science and Innovation (MCN, ‘RETOS 2019’ grant Nº PID2019-107332RB-I00), and the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Comment in

Publication types