Diagnostic and prognostic implications of coronary artery calcification detected by computed tomography
- Thomas C Gerber, MD, PhD, FACC, FAHA
Thomas C Gerber, MD, PhD, FACC, FAHA
- Professor of Medicine and Radiology
- College of Medicine, Mayo Clinic
- Christopher M Kramer, MD, FACC, FAHA
Christopher M Kramer, MD, FACC, FAHA
- Ruth C. Heede Professor of Cardiology
- Professor of Radiology
- University of Virginia Health System
- Section Editors
- Warren J Manning, MD
Warren J Manning, MD
- Section Editor — Noninvasive Cardiac Imaging and Stress Testing
- Professor of Medicine and Radiology
- Harvard Medical School
- Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
- Editor-in-Chief — Cardiovascular Medicine
- Section Editor — Coronary Heart Disease; Myopericardial Disease
- Professor of Medicine
- Mayo Clinic College of Medicine
The association between vascular calcification and vascular disease has been known to anatomists and pathologists for several hundred years. Radiologic detection of coronary artery calcification (CAC) in vivo by fluoroscopy was described in the late 1950s , and an association between the presence of CAC and the risk of cardiovascular events was subsequently demonstrated .
This topic will review the diagnostic and prognostic use of CAC. Coronary computed tomography angiography (CCTA) is discussed separately. (See "Noninvasive coronary imaging with cardiac computed tomography and cardiovascular magnetic resonance".)
CT scanner types — The development of electron beam computed tomographic scanning (EBCT) in the early 1980s permitted noninvasive and quantitative detection of CAC for the first time. The most widely used and best-established measure of CAC for assessment of the diagnostic and prognostic value of EBCT CAC scanning is the Agatston score . Other measures, such as the volume score and calcium mass have been less well studied.
Since 1999, the temporal resolution of multidetector row or multislice CT scanners (MDCT or MSCT) has improved sufficiently to permit imaging of the beating heart with no or little motion artifact. The early studies examining the diagnostic and prognostic value of CAC scanning that are discussed below have been conducted with EBCT. However, EBCT is now essentially obsolete. 64-detector MDCT is considered state-of-the-art and most newer studies of CAC have been performed with this technology. One study demonstrated that CAC scores using both volume score and Agatston score were equivalent between EBT and 64-detector MDCT .
The software used to analyze CAC has been shown to generate some variability. However, intra- and inter-scan agreement of CAC measured on the same MDCT scanner is quite high . Methods for measuring CAC from contrast-enhanced CT angiograms have been proposed . However, non-contrast scans remain the standard for making these measurements.
- BLANKENHORN DH, STERN D. Calcification of the coronary arteries. Am J Roentgenol Radium Ther Nucl Med 1959; 81:772.
- Margolis JR, Chen JT, Kong Y, et al. The diagnostic and prognostic significance of coronary artery calcification. A report of 800 cases. Radiology 1980; 137:609.
- Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15:827.
- Mao SS, Pal RS, McKay CR, et al. Comparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner. J Comput Assist Tomogr 2009; 33:175.
- Ghadri JR, Goetti R, Fiechter M, et al. Inter-scan variability of coronary artery calcium scoring assessed on 64-multidetector computed tomography vs. dual-source computed tomography: a head-to-head comparison. Eur Heart J 2011; 32:1865.
- Otton JM, Lønborg JT, Boshell D, et al. A method for coronary artery calcium scoring using contrast-enhanced computed tomography. J Cardiovasc Comput Tomogr 2012; 6:37.
- Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56:e50.
- Nakazato R, Dey D, Gutstein A, et al. Coronary artery calcium scoring using a reduced tube voltage and radiation dose protocol with dual-source computed tomography. J Cardiovasc Comput Tomogr 2009; 3:394.
- Rumberger JA, Simons DB, Fitzpatrick LA, et al. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995; 92:2157.
- Baumgart D, Schmermund A, Goerge G, et al. Comparison of electron beam computed tomography with intracoronary ultrasound and coronary angiography for detection of coronary atherosclerosis. J Am Coll Cardiol 1997; 30:57.
- Rumberger JA, Sheedy PF 3rd, Breen JF, Schwartz RS. Coronary calcium, as determined by electron beam computed tomography, and coronary disease on arteriogram. Effect of patient's sex on diagnosis. Circulation 1995; 91:1363.
- Budoff MJ, Georgiou D, Brody A, et al. Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study. Circulation 1996; 93:898.
- Kajinami K, Seki H, Takekoshi N, Mabuchi H. Coronary calcification and coronary atherosclerosis: site by site comparative morphologic study of electron beam computed tomography and coronary angiography. J Am Coll Cardiol 1997; 29:1549.
- Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316:1371.
- Haberl R, Becker A, Leber A, 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.
- Budoff MJ, Diamond GA, Raggi P, et al. Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography. Circulation 2002; 105:1791.
- Nallamothu BK, Saint S, Bielak LF, et al. Electron-beam computed tomography in the diagnosis of coronary artery disease: a meta-analysis. Arch Intern Med 2001; 161:833.
- O'Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation 2000; 102:126.
- Min JK, Lin FY, Gidseg DS, 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.
- Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999; 74:243.
- Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004; 164:1285.
- Berman DS, Wong ND, Gransar H, et al. Relationship between stress-induced myocardial ischemia and atherosclerosis measured by coronary calcium tomography. J Am Coll Cardiol 2004; 44:923.
- Raggi P, Callister TQ, Cooil B, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography. Circulation 2000; 101:850.
- Nasir K, Michos ED, Blumenthal RS, Raggi P. Detection of high-risk young adults and women by coronary calcium and National Cholesterol Education Program Panel III guidelines. J Am Coll Cardiol 2005; 46:1931.
- Budoff MJ, Hokanson JE, Nasir K, et al. Progression of coronary artery calcium predicts all-cause mortality. JACC Cardiovasc Imaging 2010; 3:1229.
- Lee TC, O'Malley PG, Feuerstein I, Taylor AJ. The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects. J Am Coll Cardiol 2003; 41:39.
- Budoff MJ, Yang TP, Shavelle RM, et al. Ethnic differences in coronary atherosclerosis. J Am Coll Cardiol 2002; 39:408.
- Bild DE, Detrano R, Peterson D, et al. Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2005; 111:1313.
- McClelland RL, Chung H, Detrano R, et al. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2006; 113:30.
- Diez Roux AV, Detrano R, Jackson S, et al. Acculturation and socioeconomic position as predictors of coronary calcification in a multiethnic sample. Circulation 2005; 112:1557.
- He ZX, Hedrick TD, Pratt CM, et al. Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia. Circulation 2000; 101:244.
- Anand DV, Lim E, Raval U, et al. Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography. J Nucl Cardiol 2004; 11:450.
- Blumenthal RS, Becker DM, Yanek LR, et al. Comparison of coronary calcium and stress myocardial perfusion imaging in apparently healthy siblings of individuals with premature coronary artery disease. Am J Cardiol 2006; 97:328.
- Wang L, Jerosch-Herold M, Jacobs DR Jr, et al. Coronary artery calcification and myocardial perfusion in asymptomatic adults: the MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2006; 48:1018.
- Schmermund A, Erbel R. Unstable coronary plaque and its relation to coronary calcium. Circulation 2001; 104:1682.
- Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation 2003; 107:2571.
- Arad Y, Spadaro LA, Goodman K, et al. Predictive value of electron beam computed tomography of the coronary arteries. 19-month follow-up of 1173 asymptomatic subjects. Circulation 1996; 93:1951.
- Arad Y, Spadaro LA, Goodman K, et al. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000; 36:1253.
- Park R, Detrano R, Xiang M, et al. Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in nondiabetic individuals. Circulation 2002; 106:2073.
- Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 2005; 46:158.
- Bielak LF, Rumberger JA, Sheedy PF 2nd, et al. Probabilistic model for prediction of angiographically defined obstructive coronary artery disease using electron beam computed tomography calcium score strata. Circulation 2000; 102:380.
- Vliegenthart R, Oudkerk M, Hofman A, et al. Coronary calcification improves cardiovascular risk prediction in the elderly. Circulation 2005; 112:572.
- Wilson PW, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837.
- National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106:3143.
- Goff DC Jr, Bertoni AG, Kramer H, et al. Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium. Circulation 2006; 113:647.
- Okwuosa TM, Greenland P, Ning H, et al. Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) potential implications for coronary risk assessment. J Am Coll Cardiol 2011; 57:1838.
- Hecht HS, Budoff MJ, Berman DS, et al. Coronary artery calcium scanning: Clinical paradigms for cardiac risk assessment and treatment. Am Heart J 2006; 151:1139.
- De Backer G, Ambrosioni E, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2003; 10:S1.
- Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions. J Am Coll Cardiol 1999; 33:1756.
- Greenland P, LaBree L, Azen SP, et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 2004; 291:210.
- Shaw LJ, Raggi P, Schisterman E, et al. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology 2003; 228:826.
- Taylor AJ, Bindeman J, Feuerstein I, et al. Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) project. J Am Coll Cardiol 2005; 46:807.
- Hopkins PN, Ellison RC, Province MA, et al. Association of coronary artery calcified plaque with clinical coronary heart disease in the National Heart, Lung, and Blood Institute's Family Heart Study. Am J Cardiol 2006; 97:1564.
- Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007; 49:1860.
- Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008; 358:1336.
- Erbel R, Möhlenkamp S, Moebus S, et al. Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol 2010; 56:1397.
- Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA 2010; 303:1610.
- Elias-Smale SE, Proença RV, Koller MT, et al. Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J Am Coll Cardiol 2010; 56:1407.
- Raggi P, Gongora MC, Gopal A, et al. Coronary artery calcium to predict all-cause mortality in elderly men and women. J Am Coll Cardiol 2008; 52:17.
- Möhlenkamp S, Lehmann N, Moebus S, et al. Quantification of coronary atherosclerosis and inflammation to predict coronary events and all-cause mortality. J Am Coll Cardiol 2011; 57:1455.
- Blaha MJ, Budoff MJ, DeFilippis AP, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet 2011; 378:684.
- Khera A, de Lemos JA, Peshock RM, et al. Relationship between C-reactive protein and subclinical atherosclerosis: the Dallas Heart Study. Circulation 2006; 113:38.
- Rana JS, Gransar H, Wong ND, et al. Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events. Am J Cardiol 2012; 109:1449.
- Yeboah J, McClelland RL, Polonsky TS, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012; 308:788.
- Shaw LJ, Raggi P, Callister TQ, Berman DS. Prognostic value of coronary artery calcium screening in asymptomatic smokers and non-smokers. Eur Heart J 2006; 27:968.
- McEvoy JW, Blaha MJ, Defilippis AP, et al. Coronary artery calcium progression: an important clinical measurement? A review of published reports. J Am Coll Cardiol 2010; 56:1613.
- Wong ND, Nelson JC, Granston T, et al. Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis study. JACC Cardiovasc Imaging 2012; 5:358.
- Budoff MJ, Young R, Lopez VA, 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.
- Waters D, Craven TE, Lespérance J. Prognostic significance of progression of coronary atherosclerosis. Circulation 1993; 87:1067.
- Folsom AR, Kronmal RA, Detrano RC, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 2008; 168:1333.
- Newman AB, Naydeck BL, Ives DG, et al. Coronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old. Am J Cardiol 2008; 101:186.
- Lester SJ, Eleid MF, Khandheria BK, Hurst RT. Carotid intima-media thickness and coronary artery calcium score as indications of subclinical atherosclerosis. Mayo Clin Proc 2009; 84:229.
- Detrano R, Hsiai T, Wang S, et al. Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography. J Am Coll Cardiol 1996; 27:285.
- Keelan PC, Bielak LF, Ashai K, et al. Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography. Circulation 2001; 104:412.
- Villines TC, Hulten EA, Shaw LJ, et al. Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry. J Am Coll Cardiol 2011; 58:2533.
- Callister TQ, Raggi P, Cooil B, et al. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 1998; 339:1972.
- Achenbach S, Ropers D, Pohle K, et al. Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation. Circulation 2002; 106:1077.
- Arad Y, Spadaro LA, Roth M, et al. 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.
- Mulders TA, Sivapalaratnam S, Stroes ES, et al. Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study. JACC Cardiovasc Imaging 2012; 5:252.
- Raggi P, Davidson M, Callister TQ, et al. Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES). Circulation 2005; 112:563.
- Schmermund A, Achenbach S, Budde T, 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.
- Redberg RF. Coronary artery calcium: should we rely on this surrogate marker? Circulation 2006; 113:336.
- O'Malley PG, Feuerstein IM, Taylor AJ. Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial. JAMA 2003; 289:2215.
- Kalia NK, Miller LG, Nasir K, et al. Visualizing coronary calcium is associated with improvements in adherence to statin therapy. Atherosclerosis 2006; 185:394.
- Orakzai RH, Nasir K, Orakzai SH, et al. Effect of patient visualization of coronary calcium by electron beam computed tomography on changes in beneficial lifestyle behaviors. Am J Cardiol 2008; 101:999.
- Rozanski A, Gransar H, Shaw LJ, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol 2011; 57:1622.
- Miedema MD, Duprez DA, Misialek JR, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes 2014; 7:453.
- Pletcher MJ, Pignone M, Earnshaw S, et al. Using the coronary artery calcium score to guide statin therapy: a cost-effectiveness analysis. Circ Cardiovasc Qual Outcomes 2014; 7:276.
- Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2007; 49:378.
- Budoff MJ, Achenbach S, Blumenthal RS, et al. Assessment of coronary artery disease by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 2006; 114:1761.
- Mozaffarian D. Electron-beam computed tomography for coronary calcium: a useful test to screen for coronary heart disease? JAMA 2005; 294:2897.
- COMPUTED TOMOGRAPHY
- CT scanner types
- CAC scanning
- Radiation exposure
- CAC AND CORONARY ARTERY STENOSIS
- CAC scoring
- Importance of ethnicity
- CAC AND MYOCARDIAL ISCHEMIA
- EMERGENCY DEPARTMENT EVALUATION OF CHEST PAIN
- CAC AND PROGNOSIS IN ASYMPTOMATIC PATIENTS
- General predictive value
- Added value to Framingham risk score
- - Identifying high-risk individuals
- - Role in moderate risk patients
- - Effect on prognosis
- Role in the elderly
- Comparison to hsCRP and other biomarkers
- Added value in smokers
- Serial measurements
- - CAC progression and risk
- Comparison with carotid intima-media thickness
- CAC AND PROGNOSIS IN SYMPTOMATIC PATIENTS
- POSSIBLE EFFECT OF TREATMENT IN ASYMPTOMATIC PATIENTS
- Observational studies
- Randomized trials
- EFFECTS ON COMPLIANCE AND RESOURCE UTILIZATION
- Resource utilization
- USE OF CAC SCORING
- SUMMARY AND RECOMMENDATIONS