title: Multiple marker approach to risk stratification in patients with stable coronary artery disease.
abstract: OBJECTIVE
  multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina.
  
  
  RESULTS
  we investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic peptide (Nt-proBNP)] in 1781 stable angina patients in relation to non-fatal myocardial infarction and cardiovascular death (n = 137) over 3.6 years. Using Cox proportional hazards models and C-indices, the strongest association with outcome for log-transformed biomarkers in multivariable-adjusted analyses was observed for Nt-proBNP [hazard ratio (HR) for one standard deviation increase 1.65, 95% confidence interval (CI) 1.28-2.13, C-index 0.686], GDF-15 (HR 1.59, 95% CI 1.25-2.02, C-index 0.681), MR-proANP (HR 1.46, 95% CI 1.14-1.87, C-index 0.673), cystatin C (HR 1.39, 95% CI 1.10-1.75, C-index 0.671), and MR-proADM (HR 1.63, 95% CI 1.21-2.20, C-index 0.668). Each of these top single markers and their combination (C-index 0.690) added predictive information beyond the baseline model consisting of the classical risk factors assessed by C-index and led to substantial reclassification (P-integrated discrimination improvement <0.05).
  
  
  CONCLUSIONS
  comparative analysis of 12 biomarkers revealed Nt-proBNP, GDF-15, MR-proANP, cystatin C, and MR-proADM as the strongest predictors of cardiovascular outcome in stable angina. All five biomarkers taken separately offered incremental predictive ability over established risk factors. Combination of the single markers slightly improved model fit but did not enhance risk prediction from a clinical perspective.
authors.affiliation: Department of Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. schnabelr@gmx.de
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulz
authors.forename: C Martina
authors.initials: CM
authors.lastname: Messow
authors.forename: Edith
authors.initials: E
authors.lastname: Lubos
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Wild
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Sinning
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Rupprecht
authors.forename: Christoph
authors.initials: C
authors.lastname: Bickel
authors.forename: Dirk
authors.initials: D
authors.lastname: Peetz
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Münzel
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
mesh_terms: D000368:Aged; D060050:Angina, Stable / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D015415:Biomarkers / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D015415:Biomarkers