Rossello · Journal of the American College of Cardiology 2021 · Cross-sectional cohort study · n=3,973

Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes.

Cited 113 times in the scientific literature.

Level 3 - non-randomized controlled study

Cross-sectional analysis within an observational cohort

PubMed 34082907 · doi:10.1016/j.jacc.2021.03.335 · record verified 2026-08-27

What was done

A cohort of 3,973 middle-aged individuals from the PESA study with no history of cardiovascular disease and HbA1c in the non-diabetic range were assessed for the presence and extent of subclinical atherosclerosis (SA) using 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography. The association between HbA1c categories and SA extent was analyzed after adjusting for established cardiovascular risk factors.

What was found

Adjusted for cardiovascular risk factors, HbA1c showed a significant association with multiterritorial SA (p < 0.001). Compared to the reference group (HbA1c <=4.8%), odds ratios were 1.05 for HbA1c 4.9% to 5.0%, 1.27 for 5.1% to 5.2%, 1.27 for 5.3% to 5.4%, 1.36 (95% CI: 1.03 to 1.80; p = 0.033) for 5.5% to 5.6%, 1.80 for 5.7% to 5.8%, 1.87 for 5.9% to 6.0%, and 2.47 for 6.1% to 6.4%. High HbA1c was associated with increased SA risk in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335).

Why it matters

This study shows that glycemic atherogenesis is detectable at HbA1c concentrations below standard pre-diabetes cutoffs. Adding HbA1c to conventional risk factors may improve early subclinical cardiovascular risk identification in non-diabetic individuals.

Limits

The cross-sectional design cannot determine temporality or causality. The cohort was limited to middle-aged individuals without cardiovascular disease, and clinical cardiovascular event outcomes were not evaluated.

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