Predictors and characterization of non-calcified plaques among patients with a zero coronary calcium score

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.

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.

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.

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.