title: Predictive value of updating Framingham risk scores with novel risk markers in the U.S. general population.
abstract: BACKGROUND
  According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population.
  
  
  RESULTS
  Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (<10%), 19% (14%) at intermediate (≥10-<20%), and 11% (6%) at high (≥20%) 10-year CVD (CHD) risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02-0.19). The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01-0.03) with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38%) moved to low and 22% (30%) to high CVD (CHD) risk. Improvements with other novel risk markers were limited.
  
  
  CONCLUSIONS
  Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands ; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Bart S
authors.initials: BS
authors.lastname: Ferket
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands ; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Bob J H
authors.initials: BJ
authors.lastname: van Kempen
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands ; Department of Radiology, Erasmus MC, Rotterdam, the Netherlands ; Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: M G Myriam
authors.initials: MG
authors.lastname: Hunink
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Isha
authors.initials: I
authors.lastname: Agarwal
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Public Health, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Institute for Health & Aging and Department of Social and Behavioral Sciences, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Wendy
authors.initials: W
authors.lastname: Max
authors.affiliation: Division of Cardiology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Fleischmann
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers