title: Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study.
abstract: BACKGROUND
  We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study.
  
  
  RESULTS
  Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%).
  
  
  CONCLUSIONS
  CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population.
authors.affiliation: Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA uhoffmann@partners.org.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Department of Mathematics, Boston University, Boston, MA The Framingham Heart Study of the National Heart, Lung and Blood Institute (NHLBI) and Boston University, Framingham, MA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Department of Mathematics, Boston University, Boston, MA The Framingham Heart Study of the National Heart, Lung and Blood Institute (NHLBI) and Boston University, Framingham, MA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.affiliation: Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA The Framingham Heart Study of the National Heart, Lung and Blood Institute (NHLBI) and Boston University, Framingham, MA Division of Intramural Research, NHLBI, Bethesda, MD.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA The Framingham Heart Study of the National Heart, Lung and Blood Institute (NHLBI) and Boston University, Framingham, MA Division of Intramural Research, NHLBI, Bethesda, MD.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
mesh_terms: D000328:Adult; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality; D001021:Aortic Valve / Q000000981:diagnostic imaging; D001027:Aortography / Q000379:methods; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D005260:Female; D006349:Heart Valve Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D008943:Mitral Valve / Q000000981:diagnostic imaging; D061330:Multidetector Computed Tomography; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000401:mortality
keywords: coronary disease; prognosis; risk factors