Regression of Atherosclerosis in Man: Current Data and Their Methodological Limitations

  • B. Greg Brown
  • Edward L. Bolson
  • Cynthia D. Pierce
  • Robert B. Peterson
  • Harold T. Dodge


The current technology with greatest precision and statistical efficiency for studying the natural course of coronary atherosclerosis is the quantitative analysis of lesion change from serial arteriograms. We have performed serial computer-assisted measurements of virtually all atherosclerotic lesions in 47 patients who were prospectively enrolled and electively recatheterized 18 months after the initial, clinically indicated, arteriogram. There were 629 coronary segments analyzed, representing the entire spectrum of minimal-to-severe atherosclerosis. The frequency distribution of change in the “percent stenosis” parameter was a bell-shaped curve centered at 1.6% (average progression in 18 months), with a standard deviation of ± 8%. Using three standard deviations of the shortterm variability of the method as a criterion for “true” lesion change, we found that 12% of all lesions progressed and 4% regressed (improved by at least 10.2% in percent stenosis). The probability of lesion change is most strongly affected by initial lesion severity and, to a lesser extent, by patient age and by hyperlipidemia. Regression thus occurred about one-third as frequently and was of lesser magnitude than progression.


Quantitative Coronary Angiography Leave Anterior Oblique Proximal Left Anterior Descend Arterial Narrowing Lesion Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. R. Malinow, P. McLaughlin, H. K. Naito, L. A. Lewis, and W. P. McNulty, Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys, Atherosclerosis 30: 37 (1978).CrossRefGoogle Scholar
  2. 2.
    D. Vesselinovitch, R. W. Wissler, R. Hughes, and J. Borensztajn, Renewal of advanced atherosclerosis in rhesus monkeys, 1: Light microscopic studies, Atherosclerosis 23: 155 (1976).CrossRefGoogle Scholar
  3. 3.
    E. B. Smith, R. S. Slater, Relationship between low-density lipoprotein in aortic intima and serum-lipid levels, Lancet 1: 463 (1972).CrossRefGoogle Scholar
  4. 4.
    M. L. Armstrong, E. D. Warner, and W. E. Conner, Regression of coronary atheromatosis in rhesus monkeys, Circ. Res. 27: 59 (1970).CrossRefGoogle Scholar
  5. 5.
    M. L. Armstrong and M. B. Megan, Lipid depletion in atheromatous coronary arteries in rhesus monkeys after regression diets, Circ. Res. 30: 675 (1972).CrossRefGoogle Scholar
  6. 6.
    M. L. Armstrong and M. B. Megan, Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets, Circ. Res. 36: 256 (1975).CrossRefGoogle Scholar
  7. 7.
    B. G. Brown and D. L. Fry, the fate and fibrogenic potential of subintimal implants oc crystalline lipid in the canine arota: Quantitative histological and autoradiographic studies, Circ. Res. 43: 261 (1978).CrossRefGoogle Scholar
  8. 8.
    H. B. Lofland and T. B. Clarkson, Bi-directional transfer of cholesterol in normal aorta, fatty streaks and atheromatous plaques. Proc. Soc. Exp. Biol. Med. 133: 1 (1970).Google Scholar
  9. 9.
    R. A. Bruce, F. Kusumi, and D. Hosmer, Maximal oxygen uptake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am. Heart J. 85: 546 (1973).CrossRefGoogle Scholar
  10. 10.
    W. B. Kannel, and P. D. Sorlie, Remission of clinical angian pectoris: The Framingham study, Am. J. Cardiol. 42: 119 (1978).CrossRefGoogle Scholar
  11. 11.
    S. Severi, G. Davies, A. Maseri, P. Marzullo, and A. l’Abbate, Long-term prognosis of “varient” angina with medical treatment, Am. J. Cardiol. 46: 226 (1980).CrossRefGoogle Scholar
  12. 12.
    The Persantine-Aspirin Reinfarction study group: Persantine and aspirin in coronary heart disease. Circulation 62: 449 (1980).CrossRefGoogle Scholar
  13. 13.
    The Norwegian Multicentre Study Group: Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N. Engl. J. Med. 304: 801 (1981).CrossRefGoogle Scholar
  14. 14.
    S. H. Taylor, B. Silke, A. Ebbutt, G. C. Sutton, B. J. Prout, and D. M. Burley. A long-term prevention study with Oxprenolol in coronary heart disease, N. Engl. J. Med. 307: 1298 (1982).Google Scholar
  15. 15.
    L. M. Zir, S. W. Miller, R. E. Dinsmore, J. P. Gilbert, and J. W. Harthorne, Interobserver variability in coronary angiography, Circulation 53: 627 (1976).CrossRefGoogle Scholar
  16. 16.
    K. M. Detre, E. Wright, M. L. Murphy, and T. Takaro, Observer agreement in evaluating coronary angiograms, Circulation 52: 979 (1975).CrossRefGoogle Scholar
  17. 17.
    R. A. Derouen, J. A. Murray, and W. Owen, Variability in the analysis of coronary arteriograms, Circulation 55: 324 (1977).CrossRefGoogle Scholar
  18. 18.
    D. Koh, S. Mitten, D. Stewart, E. Bolson, and H. T. Dodge, Comparison between computerized quantitative coronary angiography and clinical interpretation. Circulation 60 (Suppl II): 11 (1979).Google Scholar
  19. 19.
    D. P. Scoblionko, B. G. Brown, S. Mitten, J. H. Caldwell, J. W. Kennedy, E. L. Bolson, and H. T. Dodge, A new digital electronic calipier for measurement of cornary arterial stenosis: Comparison with visual estimates and computer-assisted measurements, Am. J. Cardiol., in press.Google Scholar
  20. 20.
    M. M. McMahon, B. G. Brown, R. Cukingnan, et al.: Quantitative coronary angiography: Measurement of the “critical” stenosis in patients with unstable angina and single-vessel disease without collaterals. Circulation 60: 106 (1979).CrossRefGoogle Scholar
  21. 21.
    G. G. Gensini, A. E. Kelly, B. C. B. DaCosta, and P. P. Huntington, Quantitative angiography: The measurement of coronary vasomobility in the intact animal and man, Chest 60: 522 (1971).CrossRefGoogle Scholar
  22. 22.
    R. N. MacAlphin, A. S. Abbasi, J. R. Grollman Jr., and L. Eber, Human coronary artery size during life, Radiology 108: 567 (1973).Google Scholar
  23. 23.
    D. H. Blankenhorn, S. W. Brooks, R. H. Selzer, D. W. Crawford, and H. P. Chin, Assessment of atherosclerosis from angiographic images, Proc. Soc. Exp. Biol. Med. 145: 1298 (1974).Google Scholar
  24. 24.
    W. Rafflebeul, R. Helm, M. Dzulba, B. Henkel, and P. Lichtien, Morphometric analysis of coronary arteries, in “Coronary angiography and angina pectoris,” P. R. Lichtein,, ed., George Theime Veriag, Stuttgart (1976).Google Scholar
  25. 25.
    B. G. Brown, E. Bolson, M. Frimer, and H.T. Dodge, Quantitative coronary arteriography: Estimation of dimensions, hemodynamic resistance, and atheroma mass of coronary artery lesions using the arteriogram and digital computation, Circulation 55: 329 (1977).CrossRefGoogle Scholar
  26. 26.
    R. L. Feldman, C. J. Pepine, R. C. Curry, and C. R. Conti, Quantiative coronary arteriography using 105 mm photospot angiography and an optical magnifying device, Cathet. Cardiovasc. Diagn. 5: 195 (1979).CrossRefGoogle Scholar
  27. 27.
    T. Sandor, A. B. Als, and S. Paulin, Cine-densitometric measurement of coronary arterial stenoses. Cathet. Cardiovasc. Diagn. 5: 229 (1979).CrossRefGoogle Scholar
  28. 28.
    E. L. Alderman, L. E. Berte, D. C. Harrison, and W. Sanders, Quantitation of coronary artery dimensions using digital image processings, SPIE-Digital Radiography 314: 273 (1981).CrossRefGoogle Scholar
  29. 29.
    J. H. C. Reiber, J. J. Gerbrands, C. J. Kooyman, J. C. H. Scheurbiers, C. J. Slager, A. Den Boer, and P. W. Serruys, Quantitative coronary angiography with automated contour detection and desnitometry; technical aspect, in “Angiocardiography, Current Status and Future Developments,” H. Just & P. H. Heintzen, eds., Springer-Verlag, Heidelberg (1983), in press.Google Scholar
  30. 30.
    G. G. Gensini, P. Esente, and A. Kelly, Natural history of coronary disease in patients with and without coronary bypass graft surgery, Circulation 50 (Suppl II): 11–98 (1974).Google Scholar
  31. 31.
    C. E. Bemis, R. Gorlin, H. G. Kemp, M. V. Herman, Progression of coronary artery disease. A clinical arteriographic study, Circulation 47: 455 (1973).CrossRefGoogle Scholar
  32. 32.
    D. Kimbiris, P. Lavine, H. Van Den Broek, M. Najmi, and W. Likoff, Devolutionary pattern of coronary atherosclerosis in patients with angina pectoris, Am J Cardiol 33: 7 (1974).CrossRefGoogle Scholar
  33. 33.
    D. T. Nash, N. Caldwell, and D. Ancona, Accelerated coronary artery disease arteriographically proved. Analysis of risk factors, NY State J. Med. 74: 947 (1974).Google Scholar
  34. 34.
    J. Rosch, R. Antonovic, R. S. Trenouth, S. H. Rahimtolla, D. N. Sim, and C. T. Dotter, The natural history of coronary artery stenosis, Radiology 119: 513 (1976).Google Scholar
  35. 35.
    J. R. Kramer, Y. Matsuda, J. C. Mulligan, M. Aronow, and W. L. Proudfit, Progression of Coronary Atherosclerosis, Circulation 63: 519 (1981).CrossRefGoogle Scholar
  36. 36.
    A. V. G. Bruschke, T. S. Wijers, W. Klosters, and J. Landmann, The anatomic evolution of coronary artery disease demonstrated by coronary arteriography in 256 non-operated patients, Circulation 63: 527 (1981).CrossRefGoogle Scholar
  37. 37.
    A. S. Chilvers, M. Chir, M. L. Thomas, and N. L. Browse, The progression of arteriosclerosis. A radiological study, Circulation 50: 402 (1981).CrossRefGoogle Scholar
  38. 38.
    P. T. Kup, K. Hayase, J. B. Kostis, and A. E. Moreyra, Use of combined diet and colestipol in long-term (7–7.5 years) treatment of patients with type II hyperlipoproteinemia, Circulation 59: 199 (1979).CrossRefGoogle Scholar
  39. 39.
    W. Rafflebeul, L. R. Smith, W. L. Rogers, J. A. Mantle, C. E. Rackley, and R. O. Russell Jr., Quantitative coronary arteriography. Coronary anatomy of patients with unstable angina pectoris re-examined one year after optimal medical therapy, Am. J. Cardiol. 43: 699 (1979).CrossRefGoogle Scholar
  40. 40.
    K. L. Gould, K. O. Kelley, and E. L. Bolson, Experimental validation of quantitative coronary arteriography for determining pressure-flow characteristics of coronary stenosis, Circulation 66: 930 (1982).CrossRefGoogle Scholar
  41. 41.
    D. W. Crawford, S. H. Brooks, R. H. Selzer, R. Barndt Jr., E. S. Beckenbach, and D. H. Blankenhorn, Computer densitometry for angiographic assessment of arterial cholesterol content and gross pathology in human atherosclerosis, J. Lab. Clin. Med. 89: 378 (1977).Google Scholar
  42. 42.
    B. G. Brown, C. D. Pierce, R. B. Petersen, E. L. Bolson, and H. T. Dodge, A new approach to clinical investigation of progressive coronary atherosclerosis, Circulation 60 (Suppl II): 11 (1979).Google Scholar
  43. 43.
    R. Barndt Jr., D. H. Blankenhorn, D. W. Crawford, and S. H. Brooks, Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients, Ann. Int. Med. 86: 139 (1977).CrossRefGoogle Scholar
  44. 44.
    D. H. Blankenhorn, S. H. Brooks, R. H. Selzer, and R. J. Barndt, The rate of atherosclerosis change during treatment of hyperlipoproteinemia, Circulation 57: 355 (1978).CrossRefGoogle Scholar
  45. 45.
    D. S. Fredrickson, R. I. Levy, and R. S. Lees, Fat transport in lipoproteins — an integrated approach to mechanisms and disorders, N. Eng. J. Med. 276: 32 (1967).Google Scholar
  46. 46.
    C. A. Mistretta and A. B. Crummy, Diagnosis of cardiovascular disease by digital subtraction angiography, Science 211: 761 (1981).CrossRefGoogle Scholar
  47. 47.
    J. Tobis, O. Nalcioglu, A. Seibert, B. Bauer, L. Iseri, D. Benvenuti, and W. L. Henry, Coronary angiography performed with real-time digital subtraction, Circulation 66 (Suppl II): 11 (1982).Google Scholar
  48. 48.
    G. O. Roedener, Y. E. Langlois, A. W. Chan, J. Primozich, R. J. Lawrence, P. M. Chikos, and D. E. Strandness Jr., Ultrasonic duplex scanning of extracranial carotid arteries: Improved accuracy using new features from the common carotid artery, J. Cardiovasc Ultrasonography 1: 373 (1982).Google Scholar
  49. 49.
    Y. Langlois, G. O. Roederer, A. Chen, D. J. Phillips, K. W. Beach, D. Martin, P. M. Chikos, and D. E. Strandness Jr., Evaluating carotid artery disease: The concordence between pulsed Doppler/spectrum analysis and angiography, Ultrasound in Med. and Biol. 9: 51 (1983).CrossRefGoogle Scholar
  50. 50.
    L. Kaufman, L. Crooke, P. Sheldon, H. Hricac, R. Herfkens, and W. Bank. The potential impact of nuclear magnetic resonance imaging on cardiovascular diagnosis, Circulation 67: 251 (1983).CrossRefGoogle Scholar
  51. 51.
    B. G. Brown, E. L. Bolson, and H. T. Dodge, Arteriographic assessment of coronary atherosclerosis, Arteriosclerosis 2: 2 (1982).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • B. Greg Brown
    • 1
  • Edward L. Bolson
    • 1
  • Cynthia D. Pierce
    • 1
  • Robert B. Peterson
    • 1
  • Harold T. Dodge
    • 1
  1. 1.Cardiology Division, Department of Medicine, and Cardiovascular Research & TrainingUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations