title: Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease.
abstract: BACKGROUND
  Few studies have examined simultaneously the prognostic value of traditional and emerging biomarkers including atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP), for major cardiovascular disease (CVD) outcomes in patients with stable CVD, and results are equivocal.
  
  
  METHODS
  and
  
  
  METHODS
  Mid-regional pro-ANP (MR-proANP) and N-Terminal pro-BNP (NT-proBNP), CRP and homocysteine were measured in stable CVD patients (n = 1456; age: 61.8 y) at inclusion in the SU.FOL.OM3 cohort. Prospective association of biomarkers with risk of heart failure, major cardiovascular (non-fatal myocardial infarction, ischemic stroke or death from CVD) or overall cardiovascular event were examined with Cox proportional-hazards analyses. Increase in prediction risk upon addition of biomarker(s) to the traditional risk model was examined by change in C-statistic, NRI and IDI.
  
  
  RESULTS
  During follow-up (median: 4.7 y), 40 heart failure, 145 major cardiovascular and 493 overall cardiovascular events were diagnosed. In models adjusted for age, sex, smoking, diabetes, serum creatinine and CVD inclusion criteria, NT-proBNP and CRP associated significantly with heart failure. Both natriuretic peptides predicted the risk of major cardiovascular events in adjusted models; Hazard ratio (HR) and 95% CI for each SD increase in MR-proANP and NT-proBNP were 1.24 (1.04-1.47), and 1.31 (1.09-1.57), respectively. The addition of NT-proBNP to a traditional risk model increased significantly the area-under-curve for heart failure and overall cardiovascular events (by 6 and 12%, respectively); addition of MR-proANP or homocysteine yielded modest (2%) but statistically significant increase for major cardiovascular events.
  
  
  CONCLUSIONS
  NT-proBNP consistently predicted CVD outcomes and may be useful singly or in combination with MR-proANP for risk-stratification in high-risk patients.
authors.affiliation: UMR U557 Inserm, U1125 Inra, Cnam, UFR SMBH, Université Paris 13, CRNH IdF, 74 rue Marcel Cachin, F-93017 Bobigny, France.
authors.forename: Namanjeet
authors.initials: N
authors.lastname: Ahluwalia
authors.forename: Jacques
authors.initials: J
authors.lastname: Blacher
authors.forename: Fabien
authors.initials: F
authors.lastname: Szabo de Edelenyi
authors.forename: Patrice
authors.initials: P
authors.lastname: Faure
authors.forename: Chantal
authors.initials: C
authors.lastname: Julia
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
mesh_terms: D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D016009:Chi-Square Distribution; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005602:France; D006710:Homocysteine / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D006710:Homocysteine; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein