Non-invasive assessment of coronary calcification

  • Rozemarijn VliegenthartEmail author
  • Hok-Hay S. Oei
  • Albert Hofman
  • Matthijs Oudkerk
  • Jackqueline C. M. Witteman


Electron-beam tomography (EBT) and multi-detector computed tomography (MDCT) enable the noninvasive assessment of coronary calcification. The amount of coronary calcification, as detected by EBT, has a close relation with the amount of coronary atherosclerosis, which is the substrate for the occurrence of myocardial infarction and sudden cardiac death. Calcification of the coronary arteries can be seen as a cumulative measure of life-time exposure to cardiovascular risk factors. Several studies have shown that the amount of coronary calcification is associated with the risk of coronary heart disease. Therefore, coronary calcification is a promising method for non-invasive detection of asymptomatic subjects at high risk of developing coronary heart disease. Whether measurement of coronary calcification also increases the predictive power of coronary events based on cardiovascular risk factors is topic of current research.


Atherosclerosis Epidemiology Imaging Myocardial infarction Population 


  1. Hoff, JA, Chomka, EV, Krainik, AJ, Daviglus, M, Rich, S, Kondos, GT 2001Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adultsAm J Cardiol8713351339CrossRefPubMedGoogle Scholar
  2. Raggi, P, Callister, TQ,  et al. 2000Concise review: Electron beam tomography for early detection of coronary heart diseaseBraunwald, EFauci, ASIsselbacher, KJ eds. Harrison’s OnlineMcGraw-Hill CompaniesNewYork, Scholar
  3. Goel, M, Wong, ND, Eisenberg, H, Hagar, J, Kelly, K, Tobis, JM 1992Risk factor correlates of coronary calcium as evaluated by ultrafast computed tomographyAm J Cardiol70977980CrossRefPubMedGoogle Scholar
  4. Wong, ND, Kouwabunpat, D, Vo, AN,  et al. 1994Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: Relation to age and risk factorsAm Heart J127422430CrossRefPubMedGoogle Scholar
  5. Janowitz, WR, Agatston, AS, Kaplan, G, Viamonte, M 1993Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and womenAm J Cardiol72247254CrossRefPubMedGoogle Scholar
  6. Bielak, LF, Sheedy, PF, Peyser, PA 2001Coronary artery calcification measured at electron-beam CT: Agreement in dual scan runs and change over timeRadiology218224229PubMedGoogle Scholar
  7. Hubert, HB, Feinleib, M, McNamara, PM, Castelli, WP 1983Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart StudyCirculation67968977PubMedGoogle Scholar
  8. Maher, JE, Raz, JA, Bielak, LF, Sheedy, PF,2nd, Schwartz, RS, Peyser, PA 1996Potential of quantity of coronary artery calcification to identify new risk factors for asymptomatic atherosclerosisAm J Epidemiol144943953PubMedGoogle Scholar
  9. Arad, Y, Newstein, D, Cadet, F, Roth, M, Guerci, AD 2001Association of multiple risk factors and insulin resistance with increased prevalence of asymptomatic coronary artery disease by an electron-beam computed tomographic studyArterioscler Thromb Vasc Biol2120512058PubMedCrossRefGoogle Scholar
  10. Mahoney, LT, Burns, TL, Stanford, W,  et al. 1996Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: The Muscatine StudyJ Am Coll Cardiol27277284CrossRefPubMedGoogle Scholar
  11. Newman, AB, Naydeck, BL, Sutton-Tyrrell, K, Feldman, A, Edmundowicz, D, Kuller, LH 2001Coronary artery calcification in older adults to age 99: Prevalence and risk factorsCirculation10426792684PubMedCrossRefGoogle Scholar
  12. Stokes, J,3rd, Kannel, WB, Wolf, PA, D’Agostino, RB, Cupples, LA 1989Blood pressure as a risk factor for cardiovascular disease. The Framingham Study–30 years of follow-upHypertension13I13I18PubMedGoogle Scholar
  13. 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 1999; 17: 151–183.Google Scholar
  14. O’Leary, DH, Polak, JF, Kronmal, RA,  et al. 1992Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research GroupStroke2317521760PubMedGoogle Scholar
  15. Bots, ML, Breslau, PJ, Briet, E,  et al. 1992Cardiovascular determinants of carotid artery disease. The Rotterdam Elderly StudyHypertension19717720PubMedGoogle Scholar
  16. Megnien, JL, Simon, A, Lemariey, M, Plainfosse, MC, Levenson, J 1996Hypertension promotes coronary calcium deposit in asymptomatic menHypertension27949954PubMedGoogle Scholar
  17. Jousilahti, P, Vartiainen, E, Pekkanen, J, Tuomilehto, J, Sundvall, J, Puska, P 1998Serum cholesterol distribution and coronary heart disease risk: Observations and predictions among middle-aged population in eastern FinlandCirculation9710871094PubMedGoogle Scholar
  18. Strong, JP, Richards, ML 1976Cigarette smoking and atherosclerosis in autopsied menAtherosclerosis23451476CrossRefPubMedGoogle Scholar
  19. Mintz, GS, Pichard, AD, Popma, JJ,  et al. 1997Determinants and correlates of target lesion calcium in coronary artery disease: A clinical, angiographic and intravascular ultrasound studyJ Am Coll Cardiol29268274PubMedCrossRefGoogle Scholar
  20. Tuzcu, EM, Berkalp, B, De Franco, AC,  et al. 1996The dilemma of diagnosing coronary calcification: Angiography versus intravascular ultrasoundJ Am Coll Cardiol27832838PubMedCrossRefGoogle Scholar
  21. Kornowski, R 1999Impact of smoking on coronary atherosclerosis and remodeling as determined by intravascular ultrasonic imagingAm J Cardiol83443445CrossRefPubMedGoogle Scholar
  22. Schurgin, S, Rich, S, Mazzone, T 2001Increased prevalence of significant coronary artery calcification in patients with diabetesDiabetes Care24335338PubMedCrossRefGoogle Scholar
  23. Mielke, CH, Shields, JP, Broemeling, LD 2001Coronary artery calcium, coronary artery disease, and diabetesDiabetes Res Clin Pract535561CrossRefPubMedGoogle Scholar
  24. Colhoun, HM, Rubens, MB, Underwood, SR, Fuller, JH 2000The effect of type 1 diabetes mellitus on the gender difference in coronary artery calcificationJ Am Coll Cardiol3621602167CrossRefPubMedGoogle Scholar
  25. Hoff, JA, Chomka, EV, Krainik, AJ, Daviglus, M, Rich, S, Kondos, GT 2001Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adultsAm J Cardiol8713351339CrossRefPubMedGoogle Scholar
  26. Yang, T, Doherty, TM, Wong, ND, Detrano, RC 1999Alcohol consumption, coronary calcium, and coronary heart disease eventsAm J Cardiol84802806PubMedCrossRefGoogle Scholar
  27. Hennekens, CH, Rosner, B, Cole, DS 1978Daily alcohol consumption and fatal coronary heart diseaseAm J Epidemiol107196200PubMedGoogle Scholar
  28. Klatsky, AL, Friedman, GD, Siegelaub, AB 1981Alcohol and mortality. A ten-year Kaiser-Permanente experienceAnn Intern Med95139145PubMedGoogle Scholar
  29. Suh, I, Shaten, BJ, Cutler, JA, Kuller, LH 1992Alcohol use and mortality from coronary heart disease: The role of high-density lipoprotein cholesterol. The Multiple Risk Factor Intervention Trial Research GroupAnn Intern Med116881887PubMedGoogle Scholar
  30. Camargo, CA,Jr., Stampfer, MJ, Glynn, RJ,  et al. 1997Moderate alcohol consumption and risk for angina pectoris or myocardial infarction in U.S. male physiciansAnn Intern Med126372375PubMedGoogle Scholar
  31. Ridker, PM, Buring, JE, Shih, J, Matias, M, Hennekens, CH 1998Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy womenCirculation98731733PubMedGoogle Scholar
  32. Ridker, PM, Cushman, M, Stampfer, MJ, Tracy, RP, Hennekens, CH 1997Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy menN Engl J Med336973979CrossRefPubMedGoogle Scholar
  33. Ridker, PM, Glynn, RJ, Hennekens, CH 1998C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarctionCirculation9720072011PubMedGoogle Scholar
  34. Liuzzo, G, Biasucci, LM, Gallimore, JR,  et al. 1994The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable anginaN Engl J Med331417424CrossRefPubMedGoogle Scholar
  35. Thompson, SG, Kienast, J, Pyke, SD, Haverkate, F, van de Loo, JC 1995Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris.European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study GroupN Engl J Med332635641PubMedCrossRefGoogle Scholar
  36. Haverkate, F, Thompson, SG, Pyke, SD, Gallimore, JR, Pepys, MB 1997Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study GroupLancet349462466CrossRefPubMedGoogle Scholar
  37. Kuller, LH, Tracy, RP, Shaten, J, Meilahn, EN 1996Relation of C-reactive protein and coronary heart disease in the MRFIT nested case–control study. Multiple Risk Factor Intervention TrialAm J Epidemiol144537547PubMedGoogle Scholar
  38. Ridker, PM, Cushman, M, Stampfer, MJ, Tracy, RP, Hennekens, CH 1998Plasma concentration of C-reactive protein and risk of developing peripheral vascular diseaseCirculation97425428PubMedGoogle Scholar
  39. Erren, M, Reinecke, H, Junker, R,  et al. 1999Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteriesArterioscler Thromb Vasc Biol1923552363PubMedGoogle Scholar
  40. Redberg, RF, Rifai, N, Gee, L, Ridker, PM 2000Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: Implications for coronary artery disease screeningJ Am Coll Cardiol363943CrossRefPubMedGoogle Scholar
  41. Hunt, ME, O’Malley, PG, Vernalis, MN, Feuerstein, IM, Taylor, AJ 2001C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosisAm Heart J141206210CrossRefPubMedGoogle Scholar
  42. Bielak, LF, Klee, GG, Sheedy, PF, Turner, ST, Schwartz, RS, Peyser, PA 2000Association of fibrinogen with quantity of coronary artery calcification measured by electron beam computed tomographyArterioscler Thromb Vasc Biol2021672171PubMedGoogle Scholar
  43. Maresca, G, Di Blasio, A, Marchioli, R, Di Minno, G 1999Measuring plasma fibrinogen to predict stroke and myocardial infarction: An updateArterioscler Thromb Vasc Biol1913681377PubMedGoogle Scholar
  44. Danesh, J, Collins, R, Appleby, P, Peto, R 1998Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studiesJAMA27914771482CrossRefPubMedGoogle Scholar
  45. Meade, TW, Mellows, S, Brozovic, M,  et al. 1986Haemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart StudyLancet2533537PubMedCrossRefGoogle Scholar
  46. Folsom, AR, Wu, KK, Rosamond, WD, Sharrett, AR, Chambless, LE 1997Prospective study of hemostatic factors and incidence of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) StudyCirculation9611021108PubMedGoogle Scholar
  47. Levenson, J, Giral, P, Megnien, JL, Gariepy, J, Plainfosse, MC, Simon, A 1997Fibrinogen and its relations to subclinical extracoronary and coronary atherosclerosis in hypercholesterolemic menArterioscler Thromb Vasc Biol174550PubMedGoogle Scholar
  48. Pearson, TA 2002New tools for coronary risk assessment: What are their advantages and limitations?Circulation105886892CrossRefPubMedGoogle Scholar
  49. Ford, ES, Smith, SJ, Stroup, DF, Steinberg, KK, Mueller, PW, Thacker, SB 2002Homocyst(e)ine and cardiovascular disease: A systematic review of the evidence with special emphasis on case-control studies and nested case-control studiesInt J Epidemiol315970CrossRefPubMedGoogle Scholar
  50. Zhou, J, Moller, J, Danielsen, CC,  et al. 2001Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient miceArterioscler Thromb Vasc Biol2114701476PubMedCrossRefGoogle Scholar
  51. Hofmann, MA, Lalla, E, Lu, Y,  et al. 2001Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine modelJ Clin Invest107675683PubMedCrossRefGoogle Scholar
  52. Schnyder, G, Roffi, M, Pin, R,  et al. 2001Decreased rate of coronary restenosis after lowering of plasma homocysteine levelsN Engl J Med34515931600CrossRefPubMedGoogle Scholar
  53. Taylor, AJ, Feuerstein, I, Wong, H, Barko, W, Brazaitis, M, O’Malley, PG 2001Do conventional risk factors predict subclinical coronary artery disease? Results from the Prospective Army Coronary Calcium ProjectAm Heart J141463468CrossRefPubMedGoogle Scholar
  54. Superko, HR, Hecht, HS 2001Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcificationAm J Cardiol88260264CrossRefPubMedGoogle Scholar
  55. McGill, HC,Jr., Strong, JP 1968The geographic pathology of atherosclerosisAnn NY Acad Sci149923927PubMedCrossRefGoogle Scholar
  56. Strong, JP, Malcom, GT, McMahan, CA,  et al. 1999Prevalence and extent of atherosclerosis in adolescents and young adults: Implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth StudyJAMA281727735CrossRefPubMedGoogle Scholar
  57. Freedman, DS, Newman, WP,3rd, Tracy, RE,  et al. 1988Black-white differences in aortic fatty streaks in adolescence and early adulthood: The Bogalusa Heart StudyCirculation77856864PubMedGoogle Scholar
  58. Bild, DE, Folsom, AR, Lowe, LP,  et al. 2001Prevalence and correlates of coronary calcification in black and white young adults: The Coronary Artery Risk Development in Young Adults StudyArterioscler Thromb Vasc Biol21852857PubMedGoogle Scholar
  59. Newman, AB, Naydeck, BL, Whittle, J, Sutton-Tyrrell, K, Edmundowicz, D, Kuller, LH 2002Racial differences in coronary artery calcification in older adultsArterioscler Thromb Vasc Biol22424430PubMedCrossRefGoogle Scholar
  60. Doherty, TM, Tang, W, Detrano, RC 1999Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factorsJ Am Coll Cardiol34787794CrossRefPubMedGoogle Scholar
  61. Bots, ML, Hoes, AW, Koudstaal, PJ, Hofman, A, Grobbee, DE 1997Common carotid intima-media thickness and risk of stroke and myocardial infarction: The Rotterdam StudyCirculation9614321437PubMedGoogle Scholar
  62. O’Leary, DH, Polak, JF, Kronmal, RA, Manolio, TA, Burke, GL, Wolfson, SK,Jr. 1999Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research GroupN Engl J Med3401422PubMedCrossRefGoogle Scholar
  63. Newman, AB, Shemanski, L, Manolio, TA,  et al. 1999Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study GroupArterioscler Thromb Vasc Biol19538545PubMedGoogle Scholar
  64. Witteman, JCM, Kok, FJ, van Saase, JL, Valkenburg, HA 1986Aortic calcification as a predictor of cardiovascular mortalityLancet211201122PubMedCrossRefGoogle Scholar
  65. Oei, HH, Vliegenthart, R, Hak, AE,  et al. 2002The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis: The Rotterdam Coronary Calcification StudyJ Am Coll Cardiol3917451751PubMedCrossRefGoogle Scholar
  66. Davis, PH, Dawson, JD, Mahoney, LT, Lauer, RM 1999Increased carotid intimal-medial thickness and coronary calcification are related in young and middle-aged adults. The Muscatine studyCirculation100838842PubMedGoogle Scholar
  67. Megnien, JL, Sene, V, Jeannin, S,  et al. 1992Coronary calcification and its relation to extracoronary atherosclerosis in asymptomatic hypercholesterolemic men. The PCV METRA GroupCirculation8517991807PubMedGoogle Scholar
  68. Kuller, LH, Matthews, KA, Sutton-Tyrrell, K, Edmundowicz, D, Bunker, CH 1999Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors: The healthy women studyArterioscler Thromb Vasc Biol1921892198PubMedGoogle Scholar
  69. Grover, SA, Coupal, L, Hu, XP 1995Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work?JAMA274801806CrossRefPubMedGoogle Scholar
  70. Rumberger, JA, Simons, DB, Fitzpatrick, LA, Sheedy, PF, Schwartz, RS 1995Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative studyCirculation9221572162PubMedGoogle Scholar
  71. Wexler, L, Brundage, B, Crouse, J,  et al. 1996Coronary artery calcification: Pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing GroupCirculation9411751192PubMedGoogle Scholar
  72. Arad, Y, Spadaro, LA, Goodman, K, Newstein, D, Guerci, AD 2000Prediction of coronary events with electron beam computed tomographyJ Am Coll Cardiol3612531260CrossRefPubMedGoogle Scholar
  73. Wong, ND, Hsu, JC, Detrano, RC, Diamond, G, Eisenberg, H, Gardin, JM 2000Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular eventsAm J Cardiol86495498CrossRefPubMedGoogle Scholar
  74. Raggi, P, Callister, TQ, Cooil, B,  et al. 2000Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomographyCirculation101850855PubMedGoogle Scholar
  75. Detrano, RC, Wong, ND, Doherty, TM,  et al. 1999Coronary calcium does not accurately predict near-term future coronary events in high-risk adultsCirculation9926332638PubMedGoogle Scholar
  76. Park, R, Detrano, R, Xiang, M,  et al. 2002Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in nondiabetic individualsCirculation10620732077PubMedCrossRefGoogle Scholar
  77. Vliegenthart, R, Hollander, M, Breteler, MM,  et al. 2002Stroke is associated with coronary calcification as detected by electron-beam CT: The Rotterdam Coronary Calcification StudyStroke33462465CrossRefPubMedGoogle Scholar
  78. Yoon, HC, Emerick, AM, Hill, JA, Gjertson, DW, Goldin, JG 2002Calcium begets calcium: Progression of coronary artery calcification in asymptomatic subjectsRadiology224236241PubMedCrossRefGoogle Scholar
  79. Maher, JE, Bielak, LF, Raz, JA, Sheedy, PF, Schwartz, RS, Peyser, PA 1999Progression of coronary artery calcification: A pilot studyMayo Clin Proc74347355PubMedCrossRefGoogle Scholar
  80. Pohle, K, Maffert, R, Ropers, D,  et al. 2001Progression of aortic valve calcification: Association with coronary atherosclerosis and cardiovascular risk factorsCirculation10419271932PubMedCrossRefGoogle Scholar
  81. Janowitz, WR, Agatston, AS, Viamonte, M,Jr. 1991Comparison of serial quantitative evaluation of calcified coronary artery plaque by ultrafast computed tomography in persons with and without obstructive coronary artery diseaseAm J Cardiol6816CrossRefPubMedGoogle Scholar
  82. Callister, TQ, Cooil, B, Raya, SP, Lippolis, NJ, Russo, DJ, Raggi, P 1998Coronary artery disease: Improved reproducibility of calcium scoring with an electron-beam CT volumetric methodRadiology208807814PubMedGoogle Scholar
  83. Callister, TQ, Raggi, P, Cooil, B, Lippolis, NJ, Russo, DJ 1998Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomographyN Engl J Med33919721978CrossRefPubMedGoogle Scholar
  84. Budoff, MJ, Lane, KL, Bakhsheshi, H,  et al. 2000Rates of progression of coronary calcium by electron beam tomographyAm J Cardiol86811CrossRefPubMedGoogle Scholar
  85. Achenbach, S, Ropers, D, Pohle, K,  et al. 2002Influence of lipid-lowering on the progression of coronary artery calcification: A prospective evaluationCirculation10610771082CrossRefPubMedGoogle Scholar
  86. Shemesh, J, Apter, S, Stroh, CI, Itzchak, Y, Motro, M 2000Tracking coronary calcification by using dual-section spiral CT: A 3-year follow-upRadiology217461465PubMedGoogle Scholar
  87. Shemesh, J, Apter, S, Stolero, D, Itzchak, Y, Motro, M 2001Annual progression of coronary artery calcium by spiral computed tomography in hypertensive patients without myocardial ischemia but with prominent atherosclerotic risk factors, in patients with previous angina pectoris or healed acute myocardial infarction, and in patients with coronary events during follow-upAm J Cardiol8713951397PubMedCrossRefGoogle Scholar
  88. Mielke, CH, Shields, JP, Broemeling, LD 2001Coronary artery calcium, coronary artery disease, and diabetesDiabetes Res Clin Pract535561CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Rozemarijn Vliegenthart
    • 1
    Email author
  • Hok-Hay S. Oei
    • 1
  • Albert Hofman
    • 1
  • Matthijs Oudkerk
    • 1
  • Jackqueline C. M. Witteman
    • 1
  1. 1.Department of RadiologyUniversity Hospital GroningenGroningenThe Netherlands

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