Smoking and obesity predict high-risk plaque by coronary CTA in low coronary artery calcium score (CACS)

Published:April 23, 2021DOI:



      The AHA recommends statins in patients with CACS>100 AU. However in patients with low CACS (1–99 AU), no clear statement is provided, leaving the clinician in a grey-zone. High-risk plaque (HRP) criteria by coronary CTA are novel imaging biomarkers indicating a higher a-priori cardiovascular (CV) risk, which could help for decision-making. Therefore the objective of our study was to identify which CV-risk factors predict HRP in patients with low CACS 1–99.


      1003 symptomatic patients with low-to-intermediate risk, a clinical indication for coronary computed tomography angiography (CCTA) and who had a coronary artery calcium score (CACS) between 1 and 99 AU, were enrolled. CCTA analysis included: stenosis severity and HRP-criteria: low-attenuation plaque (LAP <30HU, <60HU and <90HU) napkin-ring-sign, spotty calcification and positive remodeling. Multivariate regression models were created for predicting HRP-criteria by the major 5 cardiovascular risk factors (CVRF) (smoking, arterial hypertension, positive family history, dyslipidemia, diabetes) and obesity (BMI>25 ​kg/m2).


      304 (33.5%) were smokers. 20.4% of smokers had HRP compared with only 14.9% of non-smokers (p ​= ​0.045). Male gender was associated with HRP (p ​< ​0.001).
      Smoking but not the other 5 CVRF had the most associations with HRP-criteria (LAP<60HU/≥2 criteria:OR 1.59; 95%CI:1.07–2.35), LAP<90HU (OR 1.57; 95%CI:1.01–2.43), Napkin-Ring-Sign (OR 1.78; 95%CI:1.02–3.1) and positive remodelling (OR 1.54; 95%CI:1.09–2.19). Smoking predicted fibrofatty LAP<90HU in males only. Obesity predicted LAP<60HU in both females and males.


      In patients with low CACS 1-99AU, male gender, smoking and obesity, but not the other CVRF predict HRP. These patients would rather benefit from intensification of primary CV-prevention measures such as statins.


      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
      Full access to the journal is a member benefit for SCCT Members, Login via the SCCT website to access all journal content.


      Subscribe to Journal of Cardiovascular Computed Tomography
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Grundy S.M.
        • Stone N.J.
        • Bailey A.L.
        • et al.
        AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol.
        J Am Coll Cardiol. 2018; 73 (2019): 3168-3209
        • 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
        • 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 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
        • 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
        • Mach F.
        • Baigent C.
        • Catapano A.L.
        • et al.
        ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.
        Eur Heart J. 2019;
        • Cosentino F.
        • Grant P.J.
        • Aboyans V.
        • et al.
        ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.
        Eur Heart J. 2019;
        • 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
        • Matsumoto H.
        • Kondo T.
        • Watanabe S.
        • et al.
        ECG-edited middiastolic phase reconstruction improves image quality at 64-MDCT coronary angiography of patients with atrial fibrillation.
        AJR Am J Roentgenol. 2008; 191: 1659-1666
        • Yin W.-H.
        • Lu B.
        • Li N.
        • et al.
        Iterative reconstruction to preserve image quality and diagnostic accuracy at reduced radiation dose in coronary CT angiography.
        JACC Cardiovasc Imaging. 2013; 6: 1239-1249
        • Cury R.C.
        • Abbara S.
        • Achenbach S.
        • et al.
        CAD-RADS(TM) 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.
        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
        • 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 Hear J - Cardiovasc Imaging. 2015; 16: 373-379
        • 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
        • Cilla M.
        • Peña E.
        • Martínez M.A.
        • Kelly D.J.
        Comparison of the vulnerability risk for positive versus negative atheroma plaque morphology.
        J Biomech. 2013; 46: 1248-1254
        • Otsuka K.
        • Fukuda S.
        • Tanaka A.
        • et al.
        Napkin-ring sign on coronary CT angiography for the prediction of acute coronary syndrome.
        JACC Cardiovasc Imaging. 2013; 6: 448-457
        • Kolodgie F.D.
        • Burke A.P.
        • Farb A.
        • et al.
        Differential accumulation of proteoglycans and hyaluronan in culprit lesions.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1642-1648
        • Khan S.S.
        • Ning H.
        • Wilkins J.T.
        • et al.
        Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity.
        JAMA Cardiol. 2018; 3: 280
        • Cheezum M.K.
        • Kim A.
        • Bittencourt M.S.
        • et al.
        Association of tobacco use and cessation with coronary atherosclerosis.
        Atherosclerosis. 2017; 257: 201-207
        • Nakanishi R.
        • Berman D.S.
        • Budoff M.J.
        • et al.
        Current but not past smoking increases the risk of cardiac events: insights from coronary computed tomographic angiography.
        Eur Heart J. 2015; 36: 1031-1040
        • Messner B.
        • Bernhard D.
        Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis.
        Arterioscler Thromb Vasc Biol. 2014; 34: 509-515
        • Neufeld E.J.
        • Mietus-Snyder M.
        • Beiser A.S.
        • Baker A.L.
        • Newburger J.W.
        Passive cigarette smoking and reduced HDL cholesterol levels in children with high-risk lipid profiles.
        Circulation. 1997; 96: 1403-1407
        • Csordas A.
        • Bernhard D.
        The biology behind the atherothrombotic effects of cigarette smoke.
        Nat Rev Cardiol. 2013; 10: 219-230
        • 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: PLoS One. vol. 13. 2018e0207194 (12)
        • 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
        • Lee S.-E.
        • Chang H.-J.
        • Sung J.M.
        • et al.
        Effects of statins on coronary atherosclerotic plaques.
        JACC Cardiovasc Imaging. 2018; 11: 1475-1484
        • Williams M.C.
        • Kwiecinski J.
        • Doris M.
        • et al.
        Low-attenuation noncalcified plaque on coronary computed tomography angiography predicts myocardial infarction: results from the multicenter SCOT-heart trial (scottish computed tomography of the HEART).
        Circulation. 2020; 141: 1452-1462
        • Conte E.
        • Andreini D.
        • Magnoni M.
        • et al.
        CAPIRE investigators, steering committee; imaging core laboratory; centralized biobank and biomarker core laboratory; central ECG reading; psychologists CRF group; participating centers and investigators. Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: insight from CAPIRE study.
        J Cardiovasc Comput Tomogr. 2021; 15 (S1934-5925(20)30128-3): 73-80
        • Jang C.W.
        • Kim Y.K.
        • Kim K.H.
        • Chiara A.
        • Lee M.S.
        • Bae J.H.
        Predictors for high-risk carotid plaque in asymptomatic Korean population.
        Cardiovasc Ther. 2020 Dec 30; 2020: 6617506
        • Henzel J.
        • Kępka C.
        • Kruk M.
        • et al.
        High-risk coronary plaque regression after intensive lifestyle intervention in nonbstructive coronary disease: a randomized study.
        JACC Cardiovasc Imaging. 2020 Dec 11; (S1936-878X(20)): 30941-30944