title: Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women: A Meta-analysis.
abstract: The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear.
  
  
  
  To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.
  
  
  
  Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies.
  
  
  
  CAC score by computed tomography.
  
  
  
  Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated.
  
  
  
  Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction.
  
  
  
  Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Division of Cardiology, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Chintan S
authors.initials: CS
authors.lastname: Desai
authors.affiliation: Division of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Colby
authors.initials: C
authors.lastname: Ayers
authors.affiliation: Division of Cardiology, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Blumenthal
authors.affiliation: Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Los Angeles.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: Department of Cardiology, West German Heart and Vascular Center, University Clinic Essen, Essen, Germany.
authors.forename: Amir-Abbas
authors.initials: AA
authors.lastname: Mahabadi
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands6Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands7Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Institute for Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
authors.affiliation: Institute for Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Marie H
authors.initials: MH
authors.lastname: Geisel
authors.affiliation: Institute for Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: Institute for Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.affiliation: Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston13National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts14National Heart, Lung and Blood Institute, Bethesda, Maryland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts15Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Krankenhaus Bethanien, Department of Cardiology, Moers, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ning
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois18Senior Editor, JAMA.
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
mesh_terms: D000328:Adult; D002114:Calcinosis / Q000000981:diagnostic imaging*; D002118:Calcium / Q000032:analysis*; D009202:Cardiomyopathies / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000401:mortality; D003331:Coronary Vessels / Q000737:chemistry*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods; D020521:Stroke / Q000453:epidemiology; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology
chemical_list: D002118:Calcium