Predictors and characterization of non-calcified plaques among patients with a zero coronary calcium score
Sara Alsubai 1, Foziyah Alqahtani 2, Sara Sgreva 3, Emiliano Bianchini 4, Aduba Chukwunwike 5, Ruth Sharif 6, Hesham Elzomor 7, Naeif Almagal 8, Shahad Almotairi 9, Muhammad Yusha Malik 10, Aoife Joyce 11, Nicola Glynn 12, Michael G Madden 13, Faisal Sharif 14
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- PMID: 42632772
- DOI: 10.1016/j.jcct.2026.07.013
Free article
Abstract
Background: Non-calcified coronary atherosclerosis may be present despite a coronary artery calcium (CAC) score of zero, but its metabolic determinants are not well defined. This study investigated biomarker associations with non-calcified plaque and quantitative plaque characteristics in individuals with CAC = 0.
Methods: From a prospective registry of 860 adults underwent coronary CT angiography (CCTA) for suspected coronary artery disease, 418 individuals with CAC = 0 were analyzed. Clinical risk factors and biomarkers-including HbA1c, LDL-C, HDL-C, triglycerides, ApoA-I, ApoB, the ApoB/ApoA-I ratio, lipoprotein(a) [Lp(a)], hs-CRP, and creatine kinase-were assessed. Propensity score matching (PSM) balanced clinical risk factors (age, sex, body mass index, hypertension, hyperlipidaemia, diabetes, smoking, statin therapy, and glucose-lowering therapy) between patients with and without plaque.
Results: Non-calcified plaque was detected in 10.3% of CAC-zero individuals. Before matching, those with plaque were older (55.2 ± 10.3 vs 51.9 ± 10.5 yrs; p = 0.055) and had higher rates of hypertension, hyperlipidaemia, and diabetes, as well as higher HbA1c and Lp(a) levels. After PSM (n = 86; 43 with plaque and 43 without plaque), HbA1c remained significantly higher in individuals with plaque (39.76 ± 5.36 vs 37.60 ± 3.65 mmol/mol; p = 0.026), while other biomarkers were not significant. In exploratory analysis, elevated Lp(a) ≥50 mg/dL may be associated with greater total plaque volume (≥70 mm3) (OR 4.89, 95% CI 1.17-20.41; p = 0.03), and higher Lp(a) levels were observed in patients with low-attenuation plaque compared with those without low-attenuation plaque.
Conclusion: Among individuals with CAC = 0, higher HbA1c was associated with non-calcified coronary plaque. Elevated Lp(a) may be associated with greater plaque burden and plaque characteristics. These findings suggest a potential role for metabolic factors and CCTA in detecting subclinical atherosclerosis beyond CAC scoring.
Keywords: Cardiometabolic risk; Coronary artery calcium score; Coronary computed tomography angiography; Glycated hemoglobin; Subclinical atherosclerosis.
Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:F. Sharif is supported by the Science Foundation Ireland. The other authors have no conflict of interests to declare.
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