Predictors and characterization of non-calcified plaques among patients with a zero coronary calcium score.
Level 3 - non-randomized controlled study
Cross-sectional analysis of a prospective cohort with propensity score matching
PubMed 42632772 · doi:10.1016/j.jcct.2026.07.013
What was done
From a prospective registry of 860 adults undergoing coronary CT angiography (CCTA) for suspected coronary artery disease, 418 individuals with a coronary artery calcium (CAC) score of zero were analyzed. Researchers evaluated clinical risk factors and biomarkers (including HbA1c, LDL-C, HDL-C, triglycerides, ApoA-I, ApoB, ApoB/ApoA-I ratio, Lp(a), hs-CRP, and creatine kinase) for associations with non-calcified coronary plaque. Propensity score matching was used to balance baseline clinical characteristics between patients with and without plaque (n = 86; 43 matched pairs).
What was found
Non-calcified plaque was present in 10.3% of individuals with CAC = 0. After propensity score matching, HbA1c was significantly higher in individuals with plaque compared to those without (39.76 ± 5.36 vs 37.60 ± 3.65 mmol/mol; p = 0.026), while other biomarkers were not significantly different. In exploratory analysis, Lp(a) ≥ 50 mg/dL was associated with total plaque volume ≥ 70 mm³ (OR 4.89, 95% CI 1.17–20.41; p = 0.03), and higher Lp(a) levels were found in patients with low-attenuation plaque.
Why it matters
A CAC score of zero does not rule out coronary atherosclerosis, as roughly 1 in 10 symptomatic patients had non-calcified plaque. Higher HbA1c and elevated Lp(a) may help identify individuals with subclinical non-calcified atherosclerosis and greater plaque volume despite a zero calcium score.
Limits
The cohort consisted of patients referred for CCTA due to suspected CAD, limiting generalizability to asymptomatic populations. The propensity-matched subset was small (43 pairs), resulting in wide confidence intervals for subgroup estimates, and the cross-sectional analysis cannot establish clinical cardiovascular outcome risk or causality.
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