title: Multisite extracoronary calcification indicates increased risk of coronary heart disease and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  Cardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear.
  
  
  OBJECTIVE
  To determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality.
  
  
  METHODS
  We evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination.
  
  
  RESULTS
  Prevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03).
  
  
  CONCLUSIONS
  Increasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.
authors.affiliation: Division of Cardiology, University of California, San Francisco, Box 0124, San Francisco, CA 94143-0124, USA; Division of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: geoff.tison@ucsf.edu.
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Tison
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Mengye
authors.initials: M
authors.lastname: Guo
authors.affiliation: Division of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: McClelland
authors.affiliation: Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, San Diego, San Diego, CA, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Allison
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Moyses
authors.initials: M
authors.lastname: Szklo
authors.affiliation: Division of Cardiology, University of California, Irvine, Irvine, CA, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wong
authors.affiliation: Division of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: Division of Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001027:Aortography / Q000379:methods; D019540:Area Under Curve; D002423:Cause of Death; D003327:Coronary Disease / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality*; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality*
keywords: CHD events; Cardiovascular imaging; Extracoronary calcification; Mortality; Risk prediction