Does coronary calcium score zero reliably rule out coronary artery disease in low-to-intermediate risk patients? A coronary CTA study

Background: Objective was to assess if coronary calcium score (CCS) zero (<1.0AU) reliably rules out coronary artery disease (CAD) by coronary CTA; and if a difference between CCS zero and ultralow CCS (0.1-0.9AU) exists. Methods: 6439 low-to-intermediate ASCVD-risk patients (57.9 +/- 11.1 years; 44.4% females) who underwent CTA and CCS were enrolled. Coronary CTAs were evaluated for: (1) stenosis severity (CADRADS: <25%, 25-49%, 50-69%, 70-99%, and 100%), (2) mixed-plaque burden, and (3) high-risk-plaque-(HRP)-criteria. Primary endpoints were all-cause and cardiovascular (CV) mortality, secondary endpoint MACE. Results: Overall 1451 (22.5%) had CCS<1.0 AU. Among them, 1289 had CCS zero and 162 ultralow CCS (0.1-0.9AU). In CCS zero patients, 25.9% had CAD, 5.1% > 50% and 20.8% less than 50% stenosis, 6.8% had HRP with min 2 criteria, respectively. LAP<30HU, LAP<60HU, Napkin-Ring-Sign, Spotty calcification and PR were found in 1.3%, 3.7%, 2.8%, 2.3% and 8.2%. CAD prevalence was with 87.7% markedly higher in the ultralow CCS (p < 0.001) group, >50% stenosis (16.6%), total plaque burden (p < 0.001) and HRP-criteria rates were higher (up to 19.1%) (p < 0.001, respectively).All-cause mortality was similar (2.7% and 1.9%) in CCS 0 and ultralow patients (mean follow-up 6.6 +/- 4.2 years). Composite MACE (n = 7, 0.48%) was higher than CV-mortality (n = 1, 0.06%, p = 0.038, OR 1.08-1.6). More HRP were found on 128-slice-dual-source-CTA compared to 64-slice (p < 0.001). There were no differences in CTA findings between patients with and without chest pain, but more females were symptomatic. Conclusion: Early signs of CAD on CTA are frequent in CCS zero and even present in the majority of ultralow CCS (0.1-0.9AU) patients, who should not be downgraded to CCS zero patients. High-risk plaque and >50% stenosis rate is low but not negligible; and MACE rate very low.