title: Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.
abstract: BACKGROUND
  Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear.
  
  
  OBJECTIVE
  To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions.
  
  
  METHODS
  Prospective population-based study.
  
  
  METHODS
  The Rotterdam Study, Rotterdam, the Netherlands.
  
  
  METHODS
  5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]).
  
  
  METHODS
  Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity).
  
  
  RESULTS
  Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal.
  
  
  CONCLUSIONS
  The findings may not be generalizable to younger or nonwhite populations.
  
  
  CONCLUSIONS
  Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems.
  
  
  BACKGROUND
  Netherlands Organization for Health Research and Development (ZonMw).
authors.affiliation: Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.forename: Suzette
authors.initials: S
authors.lastname: Elias-Smale
authors.forename: Joost H W
authors.initials: JH
authors.lastname: Rutten
authors.forename: Maarten J G
authors.initials: MJ
authors.lastname: Leening
authors.forename: Rozemarijn
authors.initials: R
authors.lastname: Vliegenthart
authors.forename: Germaine C
authors.initials: GC
authors.lastname: Verwoert
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Krestin
authors.forename: Matthijs
authors.initials: M
authors.lastname: Oudkerk
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
authors.forename: Francesco U S
authors.initials: FU
authors.lastname: Mattace-Raso
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D061205:Vascular Calcification / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain