Jonas · AJR. American journal of roentgenology 2025 · nested case-control study · n=216

CTA-Derived Plaque Characteristics and Risk of Acute Coronary Syndrome in Patients With Coronary Artery Calcium Score of Zero: Insights From the ICONIC Trial.

Cited 4 times in the scientific literature.

Level 3 - non-randomized controlled study

Nested case-control analysis within a prospective multicenter registry with propensity matching

PubMed 40304673 · doi:10.2214/AJR.24.31476 · record verified 2026-08-27

What was done

This was a retrospective substudy of the prospective multicenter CONFIRM registry and its nested ICONIC cohort (data collected 2004–2010). Researchers evaluated symptomatic patients without known coronary artery disease who underwent coronary CTA and had documented coronary artery calcium (CAC) scores. Patients who subsequently developed acute coronary syndrome (ACS; n = 108) were propensity-matched 1:1 by cardiovascular risk factors and CTA disease severity to controls who did not develop ACS (n = 108). CTA datasets were analyzed using artificial intelligence software for automated quantitative plaque volume characterization, and culprit lesions were identified by invasive angiography.

What was found

Among the 216 matched patients (mean age 55.6 years; 91 women, 125 men), 23% (n = 25) of the ACS group had a CAC score of 0. In patients with ACS, culprit lesion plaque volumes (fibrous, fibrofatty, and necrotic core) did not differ significantly between those with CAC = 0 and CAC > 0 (p > .05). Within the CAC = 0 subset, patients who experienced ACS had significantly higher mean (± SD) plaque volumes than controls for fibrous plaque (29.4 ± 42.0 vs 5.5 ± 15.2 mm³, p < .001), fibrofatty plaque (27.3 ± 52.2 vs 1.3 ± 3.7 mm³, p < .001), and necrotic core (2.8 ± 6.4 vs 0.0 ± 0.1 mm³, p < .001).

Why it matters

A CAC score of zero does not preclude high-risk noncalcified coronary plaque or subsequent ACS, highlighting the potential diagnostic value of quantitative CTA plaque characterization in symptomatic patients.

Limits

The overall sample size was modest (216 patients) and the CAC = 0 ACS subgroup was small (n = 25). Plaque volume standard deviations were wide, indicating high variance. The study evaluated symptomatic patients scanned between 2004 and 2010, which may limit generalizability to asymptomatic screening populations or modern CT acquisition protocols.

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