Skip to main content
SpringerLink
Log in

Coronary Artery Disease Progression: Insights from Cardiac CT

  • Cardiac Computed Tomography (TC Villines, Section Editor)
  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

Coronary plaque progression is a multi-faceted process influenced by cardiovascular risk factors, as well as the presence, extent, stenosis, morphology, and vulnerability of plaque, which may ultimately result in myocardial infarction or death. Traditionally, intravascular ultrasound (IVUS) has been the primary modality to study atherosclerosis progression. However, it is invasive and impractical for screening or monitoring. While coronary artery calcium (CAC) scoring has been widely studied as a non-invasive method to measure plaque progression, it is limited to visualization of stenosis and non-calcified plaque. Coronary computed tomographic angiography (CCTA) allows for visualization of the severity of stenosis, plaque burden, plaque morphology, and ability to differentiate between plaque types. Furthermore, certain CCTA plaque features are useful in identifying vulnerable plaque including low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign. This review covers multiple aspects of plaque progression—its pathophysiology, clinical implications, and use of novel non-invasive technology for the assessment of plaque progression over time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull Jr W, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the committee on vascular lesions of the council on arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995;15:1512–31.

    Article  CAS  PubMed  Google Scholar 

  2. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull Jr W, Rosenfeld ME, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the committee on vascular lesions of the council on arteriosclerosis, American Heart Association. Circulation. 1994;89:2462–78.

    Article  CAS  PubMed  Google Scholar 

  3. Stary HC, Blankenhorn DH, Chandler AB, Glagov S, Insull Jr W, Richardson M, et al. A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the committee on vascular lesions of the council on arteriosclerosis, American Heart Association. Arterioscler Thromb. 1992;12:120–34.

    Article  CAS  PubMed  Google Scholar 

  4. Sakakura K, Nakano M, Otsuka F, Ladich E, Kolodgie FD, Virmani R. Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ. 2013;22:399–411.

    Article  PubMed  Google Scholar 

  5. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation. 1994;89:36–44.

    Article  PubMed  Google Scholar 

  6. Burke AP, Kolodgie FD, Farb A, Weber DK, Malcom GT, Smialek J, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation. 2001;103:934–40.

    Article  CAS  PubMed  Google Scholar 

  7. Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation. 1996;93:1354–63.

    Article  CAS  PubMed  Google Scholar 

  8. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13–8.

    Article  CAS  PubMed  Google Scholar 

  9. Kubo T, Maehara A, Mintz GS, Doi H, Tsujita K, Choi SY, et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol. 2010;55:1590–7.

    Article  CAS  PubMed  Google Scholar 

  10. Nicholls SJ, Wolski K, Sipahi I, Schoenhagen P, Crowe T, Kapadia SR, et al. Rate of progression of coronary atherosclerotic plaque in women. J Am Coll Cardiol. 2007;49:1546–51.

    Article  PubMed  Google Scholar 

  11. Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, et al. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol. 2008;52:255–62.

    Article  CAS  PubMed  Google Scholar 

  12. Bayturan O, Tuzcu EM, Lavoie A, Hu T, Wolski K, Schoenhagen P, et al. The metabolic syndrome, its component risk factors, and progression of coronary atherosclerosis. Arch Intern Med. 2010;170:478–84.

    Article  CAS  PubMed  Google Scholar 

  13. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226–35.

    Article  CAS  PubMed  Google Scholar 

  14. DeFilippis AP, Blaha MJ, Ndumele CE, Budoff MJ, Lloyd-Jones DM, McClelland RL, et al. The association of Framingham and Reynolds risk scores with incidence and progression of coronary artery calcification in MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2011;58:2076–83.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Bourantas CV, Garg S, Naka KK, Thury A, Hoye A, Michalis LK. Focus on the research utility of intravascular ultrasound—comparison with other invasive modalities. Cardiovasc Ultrasound. 2011;9:2.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation. 2002;106:2200–6.

    Article  PubMed  Google Scholar 

  17. Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217–25.

    Article  CAS  PubMed  Google Scholar 

  18. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.

    Article  CAS  PubMed  Google Scholar 

  19. Nissen SE, Tuzcu EM, Brewer HB, Sipahi I, Nicholls SJ, Ganz P, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006;354:1253–63.

    Article  CAS  PubMed  Google Scholar 

  20. Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.

    Article  CAS  PubMed  Google Scholar 

  21. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356:1304–16.

    Article  CAS  PubMed  Google Scholar 

  22. Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299:1561–73.

    Article  CAS  PubMed  Google Scholar 

  23. Nissen SE, Nicholls SJ, Wolski K, Rodes-Cabau J, Cannon CP, Deanfield JE, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA. 2008;299:1547–60.

    Article  CAS  PubMed  Google Scholar 

  24. Guagliumi G, Virmani R. The race to achieve the gold standard in coronary imaging. Rev Esp Cardiol. 2009;62:599–602.

    Article  PubMed  Google Scholar 

  25. Terashima M, Kaneda H, Suzuki T. The role of optical coherence tomography in coronary intervention. Korean J Intern Med. 2012;27:1–12.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI. Intracoronary optical coherence tomography: a comprehensive review clinical and research applications. JACC Cardiovasc Interv. 2009;2:1035–46.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol. 1998;31:126–33.

    Article  CAS  PubMed  Google Scholar 

  28. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49:1860–70.

    Article  PubMed  Google Scholar 

  29. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336–45.

    Article  CAS  PubMed  Google Scholar 

  30. Blaha M, Budoff MJ, Shaw LJ, Khosa F, Rumberger JA, Berman D, et al. Absence of coronary artery calcification and all-cause mortality. JACC Cardiovasc Imaging. 2009;2:692–700.

    Article  PubMed  Google Scholar 

  31. Min JK, Lin FY, Gidseg DS, Weinsaft JW, Berman DS, Shaw LJ, et al. Determinants of coronary calcium conversion among patients with a normal coronary calcium scan: what is the “warranty period” for remaining normal? J Am Coll Cardiol. 2010;55:1110–7.

    Article  PubMed  Google Scholar 

  32. Erbel R, Lehmann N, Churzidse S, Rauwolf M, Mahabadi AA, Mohlenkamp S, et al. Progression of coronary artery calcification seems to be inevitable, but predictable—results of the Heinz Nixdorf Recall (HNR) study. Eur Heart J. 2014;35:2960–71. In this study, Erbel et al. developed a mathematical model to predict CAC progression, demonstrating that CAC progression is nearly inevitable and cardiovascular risk factors had only a limited influence on progression.  

  33. Budoff MJ, Hokanson JE, Nasir K, Shaw LJ, Kinney GL, Chow D, et al. Progression of coronary artery calcium predicts all-cause mortality. JACC Cardiovasc Imaging. 2010;3:1229–36.

    Article  PubMed  Google Scholar 

  34. Budoff MJ, Young R, Lopez VA, Kronmal RA, Nasir K, Blumenthal RS, et al. Progression of coronary calcium and incident coronary heart disease events: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2013;61:1231–9. In this study, Budoff et al. demonstrated that progression of CAC is associated with increased risk of future myocardial infarction and fatal coronary heart disease. 

  35. Haberl R, Becker A, Leber A, Knez A, Becker C, Lang C, et al. Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients. J Am Coll Cardiol. 2001;37:451–7.

    Article  CAS  PubMed  Google Scholar 

  36. van Velzen JE, de Graaf FR, Jukema JW, de Grooth GJ, Pundziute G, Kroft LJ, et al. Comparison of the relation between the calcium score and plaque characteristics in patients with acute coronary syndrome versus patients with stable coronary artery disease, assessed by computed tomography angiography and virtual histology intravascular ultrasound. Am J Cardiol. 2011;108:658–64.

    Article  PubMed  Google Scholar 

  37. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009;54:49–57.

    Article  PubMed  Google Scholar 

  38. Maurovich-Horvat P, Schlett CL, Alkadhi H, Nakano M, Otsuka F, Stolzmann P, et al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc Imaging. 2012;5:1243–52. This study improved the diagnostic accuracy of CCTA in advancing atherosclerotic lesions by showing that a ringlike attenuation pattern of plaque known as the “napkin-ring” sign was found in patients who had acute coronary syndrome. 

  39. Voros S, Rinehart S, Qian Z, Joshi P, Vazquez G, Fischer C, et al. Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc Imaging. 2011;4:537–48.

    Article  PubMed  Google Scholar 

  40. Motoyama S, Kondo T, Anno H, Sugiura A, Ito Y, Mori K, et al. Atherosclerotic plaque characterization by 0.5-mm-slice multislice computed tomographic imaging. Circ J. 2007;71:363–6.

    Article  PubMed  Google Scholar 

  41. Voros S, Rivera JJ, Berman DS, Blankstein R, Budoff MJ, Cury RC, et al. Guideline for minimizing radiation exposure during acquisition of coronary artery calcium scans with the use of multidetector computed tomography: a report by the society for atherosclerosis imaging and prevention tomographic imaging and prevention councils in collaboration with the society of cardiovascular computed tomography. J Cardiovasc Comput Tomogr. 2011;5:75–83.

    Article  PubMed  Google Scholar 

  42. Halliburton SS, Abbara S, Chen MY, Gentry R, Mahesh M, Raff GL, et al. SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT. J Cardiovasc Comput Tomogr. 2011;5:198–224.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Lehman SJ, Schlett CL, Bamberg F, Lee H, Donnelly P, Shturman L, et al. Assessment of coronary plaque progression in coronary computed tomography angiography using a semiquantitative score. JACC Cardiovasc Imaging. 2009;2:1262–70.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Papadopoulou SL, Neefjes LA, Garcia-Garcia HM, Flu WJ, Rossi A, Dharampal AS, et al. Natural history of coronary atherosclerosis by multislice computed tomography. JACC Cardiovasc Imaging. 2012;5:S28–37. This study demonstrated the use of CCTA in following the natural history of plaque by quantifying the progression and regression of plaque. 

  45. Ito H, Motoyama S, Sarai M, Kawai H, Harigaya H, Kan S, et al. Characteristics of plaque progression detected by serial coronary computed tomography angiography. Heart Vessel. 2014;29:743–9. This study investigated variables associated with plaque progression in patients undergoing seral CCTA, showing that only LDL cholesterol at follow-up was associated with plaque progression with no specific baseline characteristics that were predictive of progression, suggesting that serial CCTA may provide insight in guiding medical treatment. 

  46. Dey D, Cheng VY, Slomka PJ, Nakazato R, Ramesh A, Gurudevan S, et al. Automated 3-dimensional quantification of noncalcified and calcified coronary plaque from coronary CT angiography. J Cardiovasc Comput Tomogr. 2009;3:372–82.

    Article  PubMed  Google Scholar 

  47. Dey D, Schepis T, Marwan M, Slomka PJ, Berman DS, Achenbach S. Automated three-dimensional quantification of noncalcified coronary plaque from coronary CT angiography: comparison with intravascular US. Radiology. 2010;257:516–22.

    Article  PubMed  Google Scholar 

  48. Schuhbaeck A, Dey D, Otaki Y, Slomka P, Kral BG, Achenbach S, et al. Interscan reproducibility of quantitative coronary plaque volume and composition from CT coronary angiography using an automated method. Eur Radiol. 2014;24:2300–8. This study confirmed the reliable interscan reproducibility of quantitative plaque measurements using AUTOPLAQ by comparing total plaque volume, volume of calcified and non-calcified plaque, and maximal remodeling index in CTAs done twice in consecutive patients.

  49. Boogers MJ, Broersen A, van Velzen JE, de Graaf FR, El-Naggar HM, Kitslaar PH, et al. Automated quantification of coronary plaque with computed tomography: comparison with intravascular ultrasound using a dedicated registration algorithm for fusion-based quantification. Eur Heart J. 2012;33:1007–16. This study used a unique co-registering algorithm to compare CT and IVUS datasets in order to demonstrate the accuracy of automated plaque quantification. 

  50. Papadopoulou SL, Garcia-Garcia HM, Rossi A, Girasis C, Dharampal AS, Kitslaar PH, et al. Reproducibility of computed tomography angiography data analysis using semiautomated plaque quantification software: implications for the design of longitudinal studies. Int J Cardiovasc Imaging. 2013;29:1095–104. This study addressed the reproducibility of inter- and intra-observer measurements for lumen, vessel, plaque area, and plaque burden, demonstrating the consistency of the measurements.  However, plaque compositional values were more variable which could be a limiting factor in CCTA studies.

  51. Blackmon KN, Streck J, Thilo C, Bastarrika G, Costello P, Schoepf UJ. Reproducibility of automated noncalcified coronary artery plaque burden assessment at coronary CT angiography. J Thorac Imaging. 2009;24:96–102.

    Article  PubMed  Google Scholar 

  52. Houslay ES, Cowell SJ, Prescott RJ, Reid J, Burton J, Northridge DB, et al. Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial. Heart. 2006;92:1207–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Schmermund A, Achenbach S, Budde T, Buziashvili Y, Forster A, Friedrich G, et al. Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial. Circulation. 2006;113:427–37.

    Article  CAS  PubMed  Google Scholar 

  54. Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis heart study randomized clinical trial. J Am Coll Cardiol. 2005;46:166–72.

    Article  CAS  PubMed  Google Scholar 

  55. Saremi A, Bahn G, Reaven PD. Progression of vascular calcification is increased with statin use in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2012;35:2390–2.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Shimojima M, Kawashiri MA, Nitta Y, Yoshida T, Katsuda S, Kaku B, et al. Rapid changes in plaque composition and morphology after intensive lipid lowering therapy: study with serial coronary CT angiography. Am J Cardiovasc Dis. 2012;2:84–8. This study used CCTA to evaluate coronary plaques in patients with suspected ACS after lipid-lowering therapy, showing that significant changes could be seen in as little as three weeks.

  57. Zeb I, Li D, Nasir K, Malpeso J, Batool A, Flores F, et al. Effect of statin treatment on coronary plaque progression—a serial coronary CT angiography study. Atherosclerosis. 2013;231:198–204. This study showed that among 100 patients who had CTA to evaluate CAD, total plaque progression was significantly reduced among statin uses, with significantly reduced progression of non-calcified plaque with no significant changes in calcified plaque, demonstrating the advantage of CCTA over CAC in classifying plaque composition. 

  58. Burgstahler C, Reimann A, Beck T, Kuettner A, Baumann D, Heuschmid M, et al. Influence of a lipid-lowering therapy on calcified and noncalcified coronary plaques monitored by multislice detector computed tomography: results of the new age II pilot study. Investig Radiol. 2007;42:189–95.

    Article  CAS  Google Scholar 

  59. Inoue K, Motoyama S, Sarai M, Sato T, Harigaya H, Hara T, et al. Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention. JACC Cardiovasc Imaging. 2010;3:691–8.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

V Yeh and R Nakanishi both declare no conflicts of interest.

MJ Budoff has received research grants from General Electric.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

Author information

Authors and Affiliations

  1. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA, 90502, USA

    Victoria Yeh, Rine Nakanishi & Matthew J. Budoff

Authors
  1. Victoria Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rine Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew J. Budoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew J. Budoff.

Additional information

This article is part of the Topical Collection on Cardiac Computed Tomography

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yeh, V., Nakanishi, R. & Budoff, M.J. Coronary Artery Disease Progression: Insights from Cardiac CT. Curr Cardiovasc Imaging Rep 8, 24 (2015). https://doi.org/10.1007/s12410-015-9341-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12410-015-9341-1

Keywords

Search

Navigation