title: Utility of Nontraditional Risk Markers in Atherosclerotic Cardiovascular Disease Risk Assessment.
abstract: BACKGROUND
  The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.
  
  
  OBJECTIVE
  This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis).
  
  
  METHODS
  The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell's C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease-related death, or fatal or nonfatal stroke.
  
  
  RESULTS
  Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell's C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell's C statistic when added to the cPCE.
  
  
  CONCLUSIONS
  CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.
authors.affiliation: Department of Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston-Salem, North Carolina. Electronic address: jyeboah@wakehealth.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yeboah
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Young
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: McClelland
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Delaney
authors.affiliation: Section of Cardiology, Department of Internal Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Tamar S
authors.initials: TS
authors.lastname: Polonsky
authors.affiliation: Department of Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston-Salem, North Carolina.
authors.forename: Farah Z
authors.initials: FZ
authors.lastname: Dawood
authors.affiliation: Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Minneapolis, Minnesota.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miedema
authors.affiliation: Radiology, Oregon Health and Science University, Portland, Oregon.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sibley
authors.affiliation: Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.affiliation: Public Health, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Burke
authors.affiliation: Public Health, University of Colorado School of Public Health, Aurora, Colorado.
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: Department of Heart and Vascular Center of Excellence, Wake Forest Baptist Health, Winston-Salem, North Carolina.
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index / Q000706:statistics & numerical data*; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D002784:Cholesterol / Q000032:analysis*; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005006:Ethnicity / Q000706:statistics & numerical data; D005192:Family Health / Q000208:ethnology / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006305:Health Status Indicators; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D002784:Cholesterol
keywords: ankle–brachial index; coronary artery calcium; high-sensitivity C-reactive protein; pooled cohort equation