medwireNews: The risk for subclinical atherosclerosis (SCA) among people at low risk for cardiovascular (CV) death increases with increasing glycated hemoglobin (HbA1c) levels and is raised even at levels below the prediabetes threshold, research shows.
Valentin Fuster (Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain) and co-investigators say their findings are “clinically relevant” because 21.2% of the 3973 participants they studied had an HbA1c level of 5.5% to 5.6% (37– 38 mmol/mol), ie the band below prediabetes according to the American Diabetes Association definition (5.7–6.4% [39–46 mmol/mol]), and would therefore not normally be considered at risk.
They add that “this subset of asymptomatic individuals [could be] a potential target for interventions aimed at preventing progression of subclinical disease to clinical events.”
Overall, the median 10-year CV mortality risk, calculated using the Systematic Coronary Risk Estimation (SCORE) equation, was 0.35% among the Progression of Early Subclinical Atherosclerosis study participants (mean age 46 years, 38% women, mean HbA1c 5.4% [36 mmol/mol]).
However, as HbA1c increased in 0.1% categories from at or below 4.8% (29 mmol/mol) to 6.1% (43 mmol/mol) and higher, the prevalence of multiterritorial SCA, as measured by 2D vascular ultrasound and noncontrast cardiac computed tomography, increased significantly from 46.0% to 82.0% overall, with that of generalized disease increasing from 4.9% to 33.1%.
After adjustment for potential confounders, including CV risk factors, the researchers found that individuals with an HbA1c of 5.5–5.6% had a significant 36% higher risk for SCA than those with an HbA1c at or below 4.8%. The risk increases were a significant 80%, 87%, and 147% for people with HbA1c of 5.7–5.8% (39–40 mmol/mol), 5.9–6.0% (41–42 mmol/mol), and 6.1–6.4% (43–46 mmol/mol), respectively.
By contrast, there was no significant association between fasting plasma glucose (FPG) and SCA, “indicating that HbA1c a is a more useful biomarker of [SCA] in people without diabetes,” the authors write in the Journal of the American College of Cardiology.
Further analysis revealed that HbA1c was associated with SCA risk in people with low CV risk (SCORE <1%) but not in those with moderate CV risk (SCORE 1–5%) and HbA1c only improved the discriminatory power of SCORE to predict CV in the low-risk population.
Specifically, SCORE alone discriminated CV risk with 73.2% accuracy in the full cohort, which increased significantly to 75.1% with the addition of HbA1c. In the low-risk population the accuracy of SCORE plus HbA1c was also 75.1%, whereas it was significantly lower, at 73.6%, in the moderate-risk population.
Commenting on these findings, editorialists Raul Santos (University of São Paulo Medical School, Brazil) et al say: “The major takeaway from this analysis is that HbA1c, and not FPG, can potentially be used as a tool to gain insight into risk of the presence and extent of SCA, and by proxy, CV [disease] risk, in individuals below the [type 2 diabetes] threshold in those considered at low CV [disease] risk.”
They add: “The observations from this study and others may provide a rationale for a clinical trial testing novel diabetes therapies focused more on presence and extent of SCA rather than an elevated HbA1c per se.”
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J Am Coll Cardiol 2021; 77: 2777–2791
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