Abstract
Background:
The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up.
Objective:
To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease.
Design:
Observational cohort.
Setting:
Single-center, outpatient cardiology laboratory.
Patients:
9715 asymptomatic patients.
Measurements:
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.
Results:
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).
Limitations:
Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once.
Conclusion:
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.
Primary Funding Source:
None.
References
- 1.
Greenland P ,Alpert JS ,Beller GA ,Benjamin EJ ,Budoff MJ ,Fayad ZA ,et al ;American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines . 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. Circulation. 2010;122:e584-636. [PMID: 21098428] doi:10.1161/CIR.0b013e3182051b4c CrossrefMedlineGoogle Scholar - 2.
Polonsky TS ,McClelland RL ,Jorgensen NW ,Bild DE ,Burke GL ,Guerci AD ,et al . Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA. 2010;303:1610-6. [PMID: 20424251] doi:10.1001/jama.2010.461 CrossrefMedlineGoogle Scholar - 3.
Shaw LJ ,Raggi P ,Schisterman E ,Berman DS ,Callister TQ . Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology. 2003;228:826-33. [PMID: 12869688] CrossrefMedlineGoogle Scholar - 4.
Wayhs R ,Zelinger A ,Raggi P . High coronary artery calcium scores pose an extremely elevated risk for hard events. J Am Coll Cardiol. 2002;39:225-30. [PMID: 11788211] CrossrefMedlineGoogle Scholar - 5.
Bellasi A ,Lacey C ,Taylor AJ ,Raggi P ,Wilson PW ,Budoff MJ ,et al . Comparison 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 Cardiol. 2007;100:409-14. [PMID: 17659919] CrossrefMedlineGoogle Scholar - 6.
Nasir K ,Shaw LJ ,Liu ST ,Weinstein SR ,Mosler TR ,Flores PR ,et al . Ethnic differences in the prognostic value of coronary artery calcification for all-cause mortality. J Am Coll Cardiol. 2007;50:953-60. [PMID: 17765122] CrossrefMedlineGoogle Scholar - 7.
Raggi P ,Gongora MC ,Gopal A ,Callister TQ ,Budoff M ,Shaw LJ . Coronary artery calcium to predict all-cause mortality in elderly men and women. J Am Coll Cardiol. 2008;52:17-23. [PMID: 18582630] doi:10.1016/j.jacc.2008.04.004 CrossrefMedlineGoogle Scholar - 8.
Oudkerk M ,Stillman AE ,Halliburton SS ,Kalender WA ,Möhlenkamp S ,McCollough CH ,et al ;European Society of Cardiac Radiology . Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol. 2008;18:2785-807. [PMID: 18651153] doi:10.1007/s00330-008-1095-6 CrossrefMedlineGoogle Scholar - 9.
Raggi P ,Shaw LJ ,Berman DS ,Callister TQ . Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol. 2004;43:1663-9. [PMID: 15120828] CrossrefMedlineGoogle Scholar - 10.
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;27:968-75. [PMID: 16443606] CrossrefMedlineGoogle Scholar - 11.
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. [PMID: 17481445] CrossrefMedlineGoogle Scholar - 12.
Mao SS ,Pal RS ,McKay CR ,Gao YG ,Gopal A ,Ahmadi N ,et al . Comparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner. J Comput Assist Tomogr. 2009;33:175-8. [PMID: 19346841] doi:10.1097/RCT.0b013e31817579ee CrossrefMedlineGoogle Scholar - 13.
Schmermund A ,Erbel R ,Silber S ;MUNICH Registry Study Group . Multislice 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 Cardiol. 2002;90:168-73. [PMID: 12106852] CrossrefMedlineGoogle Scholar - 14.
Agatston AS ,Janowitz WR ,Hildner FJ ,Zusmer NR ,Viamonte M ,Detrano R . Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;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 MJ ,D'Agostino RB ,D'Agostino RB ,Vasan RS . Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157-72. [PMID: 17569110] CrossrefMedlineGoogle Scholar - 17.
Pencina MJ ,D'Agostino RB ,Steyerberg EW . Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30:11-21. [PMID: 21204120] doi:10.1002/sim.4085 CrossrefMedlineGoogle Scholar - 18.
Bérard E ,Bongard V ,Dallongeville J ,Arveiler D ,Cottel D ,Wagner A ,et al . 14-Year risk of all-cause mortality according to hypoglycaemic drug exposure in a general population. PLoS One. 2014;9:e95671. [PMID: 24752580] doi:10.1371/journal.pone.0095671 CrossrefMedlineGoogle Scholar - 19.
Menotti A ,Mulder I ,Nissinen A ,Feskens E ,Giampaoli S ,Tervahauta M ,et al . Cardiovascular risk factors and 10-year all-cause mortality in elderly European male populations; the FINE study. Finland, Italy, Netherlands, Elderly. Eur Heart J. 2001;22:573-9. [PMID: 11259144] CrossrefMedlineGoogle Scholar - 20.
Marshall NS ,Wong KK ,Cullen SR ,Knuiman MW ,Grunstein RR . Sleep 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 Med. 2014;10:355-62. [PMID: 24733978] doi:10.5664/jcsm.3600 CrossrefMedlineGoogle Scholar - 21.
Chen Z ,Chen J ,Collins R ,Guo Y ,Peto R ,Wu F ,et al ;China Kadoorie Biobank (CKB) collaborative group . China Kadoorie Biobank of 0.5 million people: survey methods, baseline characteristics and long-term follow-up. Int J Epidemiol. 2011;40:1652-66. [PMID: 22158673] doi:10.1093/ije/dyr120 CrossrefMedlineGoogle Scholar - 22.
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. [PMID: 18367736] doi:10.1056/NEJMoa072100 CrossrefMedlineGoogle Scholar - 23.
Berry JD ,Dyer A ,Cai X ,Garside DB ,Ning H ,Thomas A ,et al . Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366:321-9. [PMID: 22276822] doi:10.1056/NEJMoa1012848 CrossrefMedlineGoogle Scholar - 24.
Steele RJ ,Brewster DH . Should we use total mortality rather than cancer specific mortality to judge cancer screening programmes? No. BMJ. 2011;343:d6397. [PMID: 21998348] doi:10.1136/bmj.d6397 CrossrefMedlineGoogle Scholar - 25.
Black WC ,Haggstrom DA ,Welch HG . All-cause mortality in randomized trials of cancer screening. J Natl Cancer Inst. 2002;94:167-73. [PMID: 11830606] CrossrefMedlineGoogle Scholar - 26.
Lauer MS ,Blackstone EH ,Young JB ,Topol EJ . Cause of death in clinical research: time for a reassessment? J Am Coll Cardiol. 1999;34:618-20. [PMID: 10483939] CrossrefMedlineGoogle Scholar - 27.
Yeboah J ,McClelland RL ,Polonsky TS ,Burke GL ,Sibley CT ,O'Leary D ,et al . Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA. 2012;308:788-95. [PMID: 22910756] doi:10.1001/jama.2012.9624 CrossrefMedlineGoogle Scholar - 28.
Taylor AJ ,Bindeman J ,Feuerstein I ,Cao F ,Brazaitis M ,O'Malley PG . 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;46:807-14. [PMID: 16139129] CrossrefMedlineGoogle Scholar - 29.
Arad Y ,Spadaro LA ,Goodman K ,Newstein D ,Guerci AD . Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol. 2000;36:1253-60. [PMID: 11028480] CrossrefMedlineGoogle Scholar - 30.
Arad Y ,Goodman KJ ,Roth M ,Newstein D ,Guerci AD . Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol. 2005;46:158-65. [PMID: 15992651] CrossrefMedlineGoogle Scholar - 31.
Erbel R ,Möhlenkamp S ,Moebus S ,Schmermund A ,Lehmann N ,Stang A ,et al ;Heinz Nixdorf Recall Study Investigative Group . Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol. 2010;56:1397-406. [PMID: 20946997] doi:10.1016/j.jacc.2010.06.030 CrossrefMedlineGoogle Scholar - 32.
Rozanski A ,Gransar H ,Wong ND ,Shaw LJ ,Miranda-Peats R ,Polk D ,et al . Clinical outcomes after both coronary calcium scanning and exercise myocardial perfusion scintigraphy. J Am Coll Cardiol. 2007;49:1352-61. [PMID: 17394969] CrossrefMedlineGoogle Scholar - 33.
Schenker MP ,Dorbala S ,Hong EC ,Rybicki FJ ,Hachamovitch R ,Kwong RY ,et al . Interrelation of coronary calcification, myocardial ischemia, and outcomes in patients with intermediate likelihood of coronary artery disease: a combined positron emission tomography/computed tomography study. Circulation. 2008;117:1693-700. [PMID: 18362235] doi:10.1161/CIRCULATIONAHA.107.717512 CrossrefMedlineGoogle Scholar - 34.
Rozanski A ,Gransar H ,Shaw LJ ,Kim J ,Miranda-Peats L ,Wong ND ,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;57:1622-32. [PMID: 21439754] doi:10.1016/j.jacc.2011.01.019 CrossrefMedlineGoogle Scholar - 35.
Smith-Bindman R ,Lipson J ,Marcus R ,Kim KP ,Mahesh M ,Gould R ,et al . Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009;169:2078-86. [PMID: 20008690] doi:10.1001/archinternmed.2009.427 CrossrefMedlineGoogle Scholar
Author, Article, and Disclosure Information
Leslee J. Shaw,
From Emory University School of Medicine, Atlanta, Georgia; Weill Cornell Medical College, New York, New York; Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Cedars-Sinai Medical Center and Harbor–UCLA Medical Center, Los Angeles, California; and Tennessee Heart and Vascular Institute, Hendersonville, Tennessee.
Disclosures: Dr. Blaha reports grants from the U.S. Food and Drug Administration/National Institutes of Health, American Heart Association, and Aetna and personal fees from Pfizer and Luitpold Pharmaceuticals outside the submitted work. Dr. Budoff reports grants from General Electric Healthcare during the conduct of the study. Dr. Min reports grants from the National Heart, Lung, and Blood Institute and National Research Foundation of Korea and other from Michael Wolk Heart Foundation and General Electric Healthcare during the conduct of the study, as well as other from Vital Images, Philips Healthcare, Arineta, AstraZeneca, Bristol-Myers Squibb, and HeartFlow outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/Conflict OfInterestForms.do?msNum=M14-0612.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Shaw (e-mail, lshaw3@emory.
Corresponding Author: Leslee J. Shaw, PhD, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1462 Clifton Road Northeast, Room 529, Atlanta, GA 30322; e-mail, leslee.
Current Author Addresses: Dr. Shaw: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1462 Clifton Road Northeast, Room 529, Atlanta, GA 30322.
Dr. Giambrone: Department of Public Health, Division of Biostatistics and Epidemiology, Weill Cornell Medical College, 402 East 67th Street, New York, NY 10065.
Dr. Blaha: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Carnegie 565A, 600 North Wolfe Street, Baltimore, MD 21287.
Dr. Knapper: Emory University School of Medicine, 116 Ponce de Leon Avenue Northeast, 2314, Atlanta, GA 30308.
Dr. Berman: Cedars-Sinai Medical Center, 8700 Beverly Boulevard, 1258 Taper Building, Los Angeles, CA 90048-0750.
Dr. Bellam: Thomas Jefferson University, 925 Chestnut Street, Philadelphia, PA 19147.
Dr. Quyyumi: Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1462 Clifton Road Northeast, Suite 507, Atlanta, GA 30322.
Dr. Budoff: Los Angeles Biomedical Research Institute, 1124 West Carson Street, Torrance, CA 90502.
Dr. Callister: Tennessee Heart and Vascular Institute, 353 New Shackle Island Road, Hendersonville, TN 37075.
Dr. Min: Dalio Institute of Cardiovascular Imaging, Weill Cornell Medical College, 525 East 68th Street, New York, NY 10065.
Author Contributions: Conception and design: L.J. Shaw, D.S. Berman, A. Quyyumi, M.J. Budoff, T.Q. Callister, J.K. Min.
Analysis and interpretation of the data: L.J. Shaw, A.E. Giambrone, M.J. Blaha, N. Bellam, M.J. Budoff, T.Q. Callister.
Drafting of the article: L.J. Shaw, N. Bellam, J.K. Min.
Critical revision of the article for important intellectual content: L.J. Shaw, M.J. Blaha, J.T. Knapper, D.S. Berman, A. Quyyumi, M.J. Budoff, T.Q. Callister, J.K. Min.
Final approval of the article: L.J. Shaw, M.J. Blaha, J.T. Knapper, D.S. Berman, A. Quyyumi, M.J. Budoff, T.Q. Callister, J.K. Min.
Provision of study materials or patients: T.Q. Callister, J.K. Min.
Statistical expertise: L.J. Shaw, A.E. Giambrone, M.J. Blaha, J.K. Min.
Obtaining of funding: J.K. Min.
Administrative, technical, or logistic support: L.J. Shaw, T.Q. Callister, J.K. Min.
Collection and assembly of data: M.J. Budoff, T.Q. Callister, J.K. Min.
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
*All comments submitted after October 1, 2021 and selected for publication will be published online only.