Original Research7 July 2015
A Cohort Study
    Author, Article, and Disclosure Information



    The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up.


    To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease.


    Observational cohort.


    Single-center, outpatient cardiology laboratory.


    9715 asymptomatic patients.


    Coronary artery calcification scoring and binary risk factor data were collected. The primary end point was time to all-cause mortality (median follow-up, 14.6 years). Univariable and multivariable Cox proportional hazards models were used to compare survival distributions. The net reclassification improvement statistic was calculated.


    In Cox models adjusted for risk factors for coronary artery disease, the CAC score was highly predictive of all-cause mortality (P < 0.001). Overall 15-year mortality rates ranged from 3% to 28% for CAC scores from 0 to 1000 or greater (P < 0.001). The relative hazard for all-cause mortality ranged from 1.68 for a CAC score of 1 to 10 (P < 0.001) to 6.26 for a score of 1000 or greater (P < 0.001). The categorical net reclassification improvement using cut points of less than 7.5% to 22.5% or greater was 0.21 (95% CI, 0.16 to 0.32).


    Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once.


    The extent of CAC accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Long-term estimates of mortality provide a unique opportunity to examine the value of novel biomarkers, such as CAC, in estimating important patient outcomes.

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    • 1. Greenland PAlpert JSBeller GABenjamin EJBudoff MJFayad ZAet alAmerican College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines2010 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. Circulation2010;122:e584-636. [PMID: 21098428] doi:10.1161/CIR.0b013e3182051b4c CrossrefMedlineGoogle Scholar
    • 2. Polonsky TSMcClelland RLJorgensen NWBild DEBurke GLGuerci ADet alCoronary artery calcium score and risk classification for coronary heart disease prediction. JAMA2010;303:1610-6. [PMID: 20424251] doi:10.1001/jama.2010.461 CrossrefMedlineGoogle Scholar
    • 3. Shaw LJRaggi PSchisterman EBerman DSCallister TQPrognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology2003;228:826-33. [PMID: 12869688] CrossrefMedlineGoogle Scholar
    • 4. Wayhs RZelinger ARaggi PHigh coronary artery calcium scores pose an extremely elevated risk for hard events. J Am Coll Cardiol2002;39:225-30. [PMID: 11788211] CrossrefMedlineGoogle Scholar
    • 5. Bellasi ALacey CTaylor AJRaggi PWilson PWBudoff MJet alComparison of prognostic usefulness of coronary artery calcium in men versus women (results from a meta- and pooled analysis estimating all-cause mortality and coronary heart disease death or myocardial infarction). Am J Cardiol2007;100:409-14. [PMID: 17659919] CrossrefMedlineGoogle Scholar
    • 6. Nasir KShaw LJLiu STWeinstein SRMosler TRFlores PRet alEthnic differences in the prognostic value of coronary artery calcification for all-cause mortality. J Am Coll Cardiol2007;50:953-60. [PMID: 17765122] CrossrefMedlineGoogle Scholar
    • 7. Raggi PGongora MCGopal ACallister TQBudoff MShaw LJCoronary artery calcium to predict all-cause mortality in elderly men and women. J Am Coll Cardiol2008;52:17-23. [PMID: 18582630] doi:10.1016/j.jacc.2008.04.004 CrossrefMedlineGoogle Scholar
    • 8. Oudkerk MStillman AEHalliburton SSKalender WAMöhlenkamp SMcCollough CHet alEuropean Society of Cardiac RadiologyCoronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol2008;18:2785-807. [PMID: 18651153] doi:10.1007/s00330-008-1095-6 CrossrefMedlineGoogle Scholar
    • 9. Raggi PShaw LJBerman DSCallister TQPrognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol2004;43:1663-9. [PMID: 15120828] CrossrefMedlineGoogle Scholar
    • 10. Shaw LJRaggi PCallister TQBerman DSPrognostic value of coronary artery calcium screening in asymptomatic smokers and non-smokers. Eur Heart J2006;27:968-75. [PMID: 16443606] CrossrefMedlineGoogle Scholar
    • 11. Budoff MJShaw LJLiu STWeinstein SRMosler TPTseng PHet alLong-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol2007;49:1860-70. [PMID: 17481445] CrossrefMedlineGoogle Scholar
    • 12. Mao SSPal RSMcKay CRGao YGGopal AAhmadi Net alComparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner. J Comput Assist Tomogr2009;33:175-8. [PMID: 19346841] doi:10.1097/RCT.0b013e31817579ee CrossrefMedlineGoogle Scholar
    • 13. Schmermund AErbel RSilber SMUNICH Registry Study GroupMultislice Normal Incidence of Coronary Health. Age and gender distribution of coronary artery calcium measured by four-slice computed tomography in 2,030 persons with no symptoms of coronary artery disease. Am J Cardiol2002;90:168-73. [PMID: 12106852] CrossrefMedlineGoogle Scholar
    • 14. Agatston ASJanowitz WRHildner FJZusmer NRViamonte MDetrano RQuantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol1990;15:827-32. [PMID: 2407762] CrossrefMedlineGoogle Scholar
    • 15. Social Security Administration. Actuarial Life Table. Accessed at www.ssa.gov/OACT/STATS/table4c6.html on 13 April 2015. Google Scholar
    • 16. Pencina MJD'Agostino RBD'Agostino RBVasan RSEvaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med2008;27:157-72. [PMID: 17569110] CrossrefMedlineGoogle Scholar
    • 17. Pencina MJD'Agostino RBSteyerberg EWExtensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med2011;30:11-21. [PMID: 21204120] doi:10.1002/sim.4085 CrossrefMedlineGoogle Scholar
    • 18. Bérard EBongard VDallongeville JArveiler DCottel DWagner Aet al14-Year risk of all-cause mortality according to hypoglycaemic drug exposure in a general population. PLoS One2014;9:e95671. [PMID: 24752580] doi:10.1371/journal.pone.0095671 CrossrefMedlineGoogle Scholar
    • 19. Menotti AMulder INissinen AFeskens EGiampaoli STervahauta Met alCardiovascular risk factors and 10-year all-cause mortality in elderly European male populations; the FINE study. Finland, Italy, Netherlands, Elderly. Eur Heart J2001;22:573-9. [PMID: 11259144] CrossrefMedlineGoogle Scholar
    • 20. Marshall NSWong KKCullen SRKnuiman MWGrunstein RRSleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. J Clin Sleep Med2014;10:355-62. [PMID: 24733978] doi:10.5664/jcsm.3600 CrossrefMedlineGoogle Scholar
    • 21. Chen ZChen JCollins RGuo YPeto RWu Fet alChina Kadoorie Biobank (CKB) collaborative groupChina Kadoorie Biobank of 0.5 million people: survey methods, baseline characteristics and long-term follow-up. Int J Epidemiol2011;40:1652-66. [PMID: 22158673] doi:10.1093/ije/dyr120 CrossrefMedlineGoogle Scholar
    • 22. Detrano RGuerci ADCarr JJBild DEBurke GFolsom ARet alCoronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med2008;358:1336-45. [PMID: 18367736] doi:10.1056/NEJMoa072100 CrossrefMedlineGoogle Scholar
    • 23. Berry JDDyer ACai XGarside DBNing HThomas Aet alLifetime risks of cardiovascular disease. N Engl J Med2012;366:321-9. [PMID: 22276822] doi:10.1056/NEJMoa1012848 CrossrefMedlineGoogle Scholar
    • 24. Steele RJBrewster DHShould we use total mortality rather than cancer specific mortality to judge cancer screening programmes? No. BMJ2011;343:d6397. [PMID: 21998348] doi:10.1136/bmj.d6397 CrossrefMedlineGoogle Scholar
    • 25. Black WCHaggstrom DAWelch HGAll-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst2002;94:167-73. [PMID: 11830606] CrossrefMedlineGoogle Scholar
    • 26. Lauer MSBlackstone EHYoung JBTopol EJCause of death in clinical research: time for a reassessment? J Am Coll Cardiol1999;34:618-20. [PMID: 10483939] CrossrefMedlineGoogle Scholar
    • 27. Yeboah JMcClelland RLPolonsky TSBurke GLSibley CTO'Leary Det alComparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA2012;308:788-95. [PMID: 22910756] doi:10.1001/jama.2012.9624 CrossrefMedlineGoogle Scholar
    • 28. Taylor AJBindeman JFeuerstein ICao FBrazaitis MO'Malley PGCoronary 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 Cardiol2005;46:807-14. [PMID: 16139129] CrossrefMedlineGoogle Scholar
    • 29. Arad YSpadaro LAGoodman KNewstein DGuerci ADPrediction of coronary events with electron beam computed tomography. J Am Coll Cardiol2000;36:1253-60. [PMID: 11028480] CrossrefMedlineGoogle Scholar
    • 30. Arad YGoodman KJRoth MNewstein DGuerci ADCoronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol2005;46:158-65. [PMID: 15992651] CrossrefMedlineGoogle Scholar
    • 31. Erbel RMöhlenkamp SMoebus SSchmermund ALehmann NStang Aet alHeinz Nixdorf Recall Study Investigative GroupCoronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol2010;56:1397-406. [PMID: 20946997] doi:10.1016/j.jacc.2010.06.030 CrossrefMedlineGoogle Scholar
    • 32. Rozanski AGransar HWong NDShaw LJMiranda-Peats RPolk Det alClinical outcomes after both coronary calcium scanning and exercise myocardial perfusion scintigraphy. J Am Coll Cardiol2007;49:1352-61. [PMID: 17394969] CrossrefMedlineGoogle Scholar
    • 33. Schenker MPDorbala SHong ECRybicki FJHachamovitch RKwong RYet alInterrelation of coronary calcification, myocardial ischemia, and outcomes in patients with intermediate likelihood of coronary artery disease: a combined positron emission tomography/computed tomography study. Circulation2008;117:1693-700. [PMID: 18362235] doi:10.1161/CIRCULATIONAHA.107.717512 CrossrefMedlineGoogle Scholar
    • 34. Rozanski AGransar HShaw LJKim JMiranda-Peats LWong NDet alImpact 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 Cardiol2011;57:1622-32. [PMID: 21439754] doi:10.1016/j.jacc.2011.01.019 CrossrefMedlineGoogle Scholar
    • 35. Smith-Bindman RLipson JMarcus RKim KPMahesh MGould Ret alRadiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med2009;169:2078-86. [PMID: 20008690] doi:10.1001/archinternmed.2009.427 CrossrefMedlineGoogle Scholar