title: Multiple biomarkers for the prediction of first major cardiovascular events and death.
abstract: BACKGROUND
  Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events.
  
  
  METHODS
  We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio.
  
  
  RESULTS
  During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic.
  
  
  CONCLUSIONS
  For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.
authors.affiliation: Framingham Heart Study, Framingham, MA, USA. tjwang@partners.org
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Philimon
authors.initials: P
authors.lastname: Gona
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Tofler
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Robins
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D015415:Biomarkers / Q000097:blood* / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D002097:C-Reactive Protein