title: Improving the CAC Score by Addition of Regional Measures of Calcium Distribution: Multi-Ethnic Study of Atherosclerosis.
abstract: The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events.
  
  
  
  Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque.
  
  
  
  We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The "diffusivity index" was calculated as: 1 - (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score.
  
  
  
  Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ≥2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction.
  
  
  
  The number of coronary arteries with calcified plaque, indicating increasingly "diffuse" multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland. Electronic address: mblaha1@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Division of Cardiology, Danbury Hospital, Danbury, Connecticut.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Tota-Maharaj
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Zeina A
authors.initials: ZA
authors.lastname: Dardari
authors.affiliation: Division of Cardiology, University of California-Irvine, Irvine, California.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wong
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
authors.affiliation: Department of Radiology, Johns Hopkins, Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Eng
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida.
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002118:Calcium / Q000032:analysis*; D000072226:Computed Tomography Angiography; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000208:ethnology / Q000378:metabolism; D003331:Coronary Vessels / Q000737:chemistry / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000000981:diagnostic imaging* / Q000208:ethnology / Q000378:metabolism
chemical_list: D002118:Calcium
keywords: cardiac computed tomography; risk prediction; risk stratification