Added value of high-risk plaque criteria by coronary CTA for prediction of long-term outcomes


      • High-risk plaque criteria are associated with increased morbidity and mortality.
      • Stenosis severity by computed tomography angiography (CTA) predicts all-cause and cardiovascular mortality.
      • Plaque burden, low-attenuation-plaque (LAP) <60HU and napkin-ring predict major adverse cardiovascular events (MACE), but not all-cause mortality.
      • Patients with negative CTA for coronary artery disease have an excellent long-term prognosis.


      Background and aims

      Long-term data relating coronary computed tomography angiography (CTA) to coronary artery disease (CAD) prognosis including novel CTA-biomarkers (“high–risk plaque criteria”) is scarce. The aim of this study was to define predictors of long-term outcomes.


      1430 low-to-intermediate risk patients (57.9 ± 11.1 years; 44.4% females) who underwent CTA and coronary calcium scoring (CCS) were prospectively enrolled. CTAs were evaluated for (1) stenosis severity CADRADS 0–4 (minimal <25%, mild 25–50%, moderate 50–70%, severe >70%), (2) mixed plaque burden weighted for non-calcified plaque (NCP), and (3) high-risk-plaque (HRP) criteria: low-attenuation-plaque (LAP), napkin-ring-sign, spotty calcifications <3 mm or remodeling index >1.1. Endpoints were all-cause and cardiovascular mortality, composite fatal and nonfatal major adverse cardiovascular events (MACE).


      Over a mean follow-up of 10.55 years ± 1.98, 106 patients (7.4%) died, 25 from cardiovascular events (1.75%). Composite MACE occurred in 57 (3.9%) patients. In patients with negative CTA, cardiovascular mortality and MACE rates were 0% and 0.2%.
      Stenosis severity by CTA predicted all 3 endpoints (p < 0.001) while CCS >100 AU predicted only all-cause mortality (p = 0.045) but not MACE.
      The high risk plaque criteria LAP <60HU (HR: 4.00, 95%CI 95% 1.52–10.52, p = 0.005) and napkin-ring (HR 4.11, CI 95% 1.77–9.52, p = 0.001) predicted MACE but not all-cause-mortality, after adjusting for risk factors, while spotty calcification and remodeling index did not. Similarly, mixed plaque burden predicted MACE (p < 0.0001).
      HRP criteria, if added to CADRADS + CCS for prediction of MACE, were superior to CCS (c = 0.816 vs 0.716, p < 0.001). In 33.5% of CCS zero patients, non-calcified fibroatheroma were found.


      Long-term prognosis is excellent if CTA is negative for CAD. The high-risk plaque criteria LAP<60HU and napkin-ring-sign were independent predictors of MACE while HRP criteria added incremental prognostic value.

      Graphical abstract


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Douglas P.S.
        • Hoffmann U.
        • Patel M.R.
        • et al.
        Outcomes of anatomical versus functional testing for coronary artery disease.
        N. Engl. J. Med. 2015; 372: 1291-1300
        • Newby D.E.
        • Adamson P.D.
        • et al.
        • SCOT-HEART Investigators
        Coronary CT angiography and 5-year risk of myocardial infarction.
        N. Engl. J. Med. 2018; 379: 924-933
        • Finck T.
        • Hardenberg J.
        • Will A.
        • et al.
        10-Year follow-up after coronary computed tomography angiography in patients with suspected coronary artery disease.
        JACC Cardiovasc Imaging. 2019; 12: 1330-1338
        • Halon D.A.
        • Lavi I.
        • Barnett-Griness O.
        • et al.
        Plaque morphology as predictor of late plaque events in patients with asymptomatic type 2 diabetes: a long-term observational study.
        JACC Cardiovasc Imaging. 2019; 12: 1353-1363
        • Maurovich-Horvat P.
        • Schlett C.L.
        • Alkadhi H.
        • et al.
        The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography.
        JACC Cardiovasc Imaging. 2012; 5: 1243-1252
        • Nakazato R.
        • Otake H.
        • Konishi A.
        • et al.
        Atherosclerotic plaque characterization by CT angiography for identification of high-risk coronary artery lesions: a comparison to optical coherence tomography.
        Eur Heart J Cardiovasc Imaging. 2015; 16: 373-379
        • Motoyama S.
        • Ito H.
        • Sarai M.
        • et al.
        Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up.
        J. Am. Coll. Cardiol. 2015; 66: 337-346
        • Feuchtner G.
        • Kerber J.
        • Burghard P.
        • et al.
        The high-risk criteria low-attenuation plaque <60 HU and the napkin-ring sign are the most powerful predictors of MACE: a long-term follow-up study.
        Eur Heart J Cardiovasc Imaging. 2017; 18: 772-779
        • Ferencik M.
        • Mayrhofer T.
        • Bittner D.O.
        • et al.
        Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: a secondary analysis of the PROMISE randomized clinical trial.
        JAMA Cardiol. 2018; 3: 144-152
        • Thomsen C.
        • Abdulla J.
        Characteristics of high-risk coronary plaques identified by computed tomographic angiography and associated prognosis: a systematic review and meta-analysis.
        Eur Heart J Cardiovasc Imaging. 2016; 17: 120-129
        • Goff D.C.
        • Lloyd-Jones D.M.
        • Bennett G.
        • et al.
        ACC/AHA guideline on the assessment of cardiovascular risk.
        J. Am. Coll. Cardiol. 2013; 63 (2014): 2935-2959
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • et al.
        ESC/EAS guidelines for the management of dyslipidaemias.
        Eur. Heart J. 2016; 37 (2016): 2999-3058
        • Williams B.
        • Mancia G.
        • Spiering W.
        • et al.
        ESC/ESH Guidelines for the management of arterial hypertension.
        Eur. Heart J. 2018; 39 (2018): 3021-3104
        • Anderson J.L.
        • Adams C.D.
        • Antman E.M.
        • et al.
        ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable Angina/non-ST-elevation myocardial infarction: a report of the American college of Cardiology foundation/American heart association task force on practice guidelines.
        Circulation. 2011; 123 (2011): e426-579
        • Agatston A.S.
        • Janowitz W.R.
        • Hildner F.J.
        • Zusmer N.R.
        • Viamonte M.
        • Detrano R.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J. Am. Coll. Cardiol. 1990; 15: 827-832
        • Cury R.C.
        • Abbara S.
        • Achenbach S.
        • et al.
        CAD-RADSTM coronary artery disease – reporting and data system. An expert consensus document of the society of cardiovascular computed tomography (SCCT), the American college of radiology (ACR) and the North American society for cardiovascular imaging (NASCI). Endorsed by the American college of Cardiology.
        J Cardiovasc Comput Tomogr. 2016; 10: 269-281
        • Austen W.G.
        • Edwards J.E.
        • Frye R.L.
        • et al.
        A reporting system on patients evaluated for coronary artery disease. Report of the ad hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American heart association.
        Circulation. 1975; 51: 5-40
        • Leber A.W.
        • Knez A.
        • Becker A.
        • et al.
        Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound.
        J. Am. Coll. Cardiol. 2004; 43: 1241-1247
        • Feuchtner G.M.
        • Barbieri F.
        • Langer C.
        • et al.
        Non obstructive high-risk plaque but not calcified by coronary CTA, and the G-score predict ischemia.
        J Cardiovasc Comput Tomogr. January 2019; 13: 305-314
        • Williams M.C.
        • Moss A.J.
        • Dweck M.
        • et al.
        Coronary artery plaque characteristics associated with adverse outcomes in the SCOT-heart study.
        J. Am. Coll. Cardiol. 2019; 73: 291-301
        • Cheruvu C.
        • Precious B.
        • Naoum C.
        • et al.
        Long term prognostic utility of coronary CT angiography in patients with no modifiable coronary artery disease risk factors: results from the 5 year follow-up of the CONFIRM International Multicenter Registry.
        J Cardiovasc Comput Tomogr. 2016; 10: 22-27
        • Cho Y.-K.
        • Nam C.-W.
        • Koo B.-K.
        • et al.
        Usefulness of Baseline Statin Therapy in Non-obstructive Coronary Artery Disease by Coronary Computed Tomographic Angiography: from the CONFIRM (COronary CT Angiography EvaluatioN for Clinical Outcomes: an InteRnational Multicenter) Study.
        in: Novo G. PloS One. 2018e0207194 (vol. 13(12))
        • Finck T.
        • Hardenberg J.
        • Will A.
        • et al.
        10-Year follow-up after coronary computed tomography angiography in patients with suspected coronary artery disease.
        JACC Cardiovasc Imaging. 2019; 12: 1330-1338
        • Hadamitzky M.
        • Achenbach S.
        • Al-Mallah M.
        • et al.
        Optimized prognostic score for coronary computed tomographic angiography: results from the CONFIRM registry (COronary CT Angiography EvaluatioN for Clinical Outcomes: an InteRnational Multicenter Registry).
        J. Am. Coll. Cardiol. 2013; 62: 468-476
        • Hell M.M.
        • Motwani M.
        • Otaki Y.
        • et al.
        Quantitative global plaque characteristics from coronary computed tomography angiography for the prediction of future cardiac mortality during long-term follow-up.
        Eur Heart J Cardiovasc Imaging. 2017; 18: 1331-1339
        • Ahmadi A.
        • Leipsic J.
        • Øvrehus K.A.
        • et al.
        Lesion-specific and vessel-related determinants of fractional flow reserve beyond coronary artery stenosis.
        JACC Cardiovasc Imaging. 2018; 11: 521-530
        • Senoner T.
        • Plank F.
        • Beyer C.
        • et al.
        Does coronary calcium score zero reliably rule out coronary artery disease in low-to-intermediate risk patients? A coronary CTA study.
        J Cardiovasc Comput Tomogr. September 2019;
        • Lee S.E.
        • Chang H.J.
        • Sung J.M.
        • et al.
        Effects of statins on coronary atherosclerotic plaques: the PARADIGM study.
        JACC Cardiovasc Imaging. 2018; 11: 1475-1484
        • Chhatriwalla A.K.
        • Nicholls S.J.
        • Nissen S.E.
        The ASTEROID trial: coronary plaque regression with high-dose statin therapy.
        Future Cardiol. 2006; 2: 651-654
        • Nicholls S.J.
        • Puri R.
        • Anderson T.
        • et al.
        Effect of evolocumab on progression of coronary disease in statin-treated patients.
        J. Am. Med. Assoc. 2016; 316: 2373