title: Evaluation of 9 biomarkers for predicting 10-year cardiovascular risk in patients undergoing coronary angiography: findings from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study.
abstract: BACKGROUND
  Conventional factors do not fully explain the distribution of cardiovascular outcomes. Biomarkers are known to participate in well-established pathways associated with cardiovascular disease, and may therefore provide further information over and above conventional risk factors. This study sought to determine whether individual and/or combined assessment of 9 biomarkers improved discrimination, calibration and reclassification of cardiovascular mortality.
  
  
  METHODS
  3267 patients (2283 men), aged 18-95 years, at intermediate-to-high-risk of cardiovascular disease were followed in this prospective cohort study. Conventional risk factors and biomarkers were included based on forward and backward Cox proportional stepwise selection models.
  
  
  RESULTS
  During 10-years of follow-up, 546 fatal cardiovascular events occurred. Four biomarkers (interleukin-6, neutrophils, von Willebrand factor, and 25-hydroxyvitamin D) were retained during stepwise selection procedures for subsequent analyses. Simultaneous inclusion of these biomarkers significantly improved discrimination as measured by the C-index (0.78, P = 0.0001), and integrated discrimination improvement (0.0219, P<0.0001). Collectively, these biomarkers improved net reclassification for cardiovascular death by 10.6% (P<0.0001) when added to the conventional risk model.
  
  
  CONCLUSIONS
  In terms of adverse cardiovascular prognosis, a biomarker panel consisting of interleukin-6, neutrophils, von Willebrand factor, and 25-hydroxyvitamin D offered significant incremental value beyond that conveyed by simple conventional risk factors.
authors.affiliation: Department of Internal Medicine/Geriatrics, Yale School of Medicine, Yale University, 06510 New Haven, USA; Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, UK.
authors.forename: Bríain
authors.initials: B
authors.lastname: Omicron Hartaigh
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.forename: Jos A
authors.initials: JA
authors.lastname: Bosch
authors.forename: Karla
authors.initials: K
authors.lastname: Hemming
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Adrian
authors.initials: A
authors.lastname: Loerbroks
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Fischer
authors.forename: Guenther
authors.initials: G
authors.lastname: Silbernagel
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Biomarker; Cardiovascular; Discrimination; Reclassification; Risk factor