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Original Investigation
November 22/29, 2016

Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk WomenA Meta-analysis

Author Affiliations
  • 1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 2Division of Cardiology, Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins Medical Institutions, Baltimore, Maryland
  • 3Division of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas
  • 4Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Los Angeles
  • 5Department of Cardiology, West German Heart and Vascular Center, University Clinic Essen, Essen, Germany
  • 6Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 7Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 9Institute for Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany
  • 10Division of Cardiology, University of Texas Southwestern Medical Center, Dallas
  • 11Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston
  • 12Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
  • 13National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts
  • 14National Heart, Lung and Blood Institute, Bethesda, Maryland
  • 15Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  • 16Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
  • 17Krankenhaus Bethanien, Department of Cardiology, Moers, Germany
  • 18Senior Editor, JAMA
JAMA. 2016;316(20):2126-2134. doi:10.1001/jama.2016.17020
Key Points

Question  What is the value of coronary artery calcium (CAC) for cardiovascular risk assessment among women with 10-year atherosclerotic cardiovascular disease (ASCVD) risk less than 7.5% (low risk of CVD)?

Findings  Among 6739 low-risk women from 5 large population-based cohorts, compared with CAC absence, CAC presence 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). Addition of CAC to traditional risk factors led to modest improvement in prognostic accuracy.

Meaning  Among women at low risk of ASCVD, 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.

Abstract

Importance  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.

Objective  To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.

Design, Setting, and Participants  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.

Exposures  CAC score by computed tomography.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

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