Multiple marker approach to risk stratification in patients with stable coronary artery disease.
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.
Schnabel
Renate B
RB
Department of Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. schnabelr@gmx.de
Schulz
Andreas
A
Messow
C Martina
CM
Lubos
Edith
E
Wild
Philipp S
PS
Zeller
Tanja
T
Sinning
Christoph R
CR
Rupprecht
Hans J
HJ
Bickel
Christoph
C
Peetz
Dirk
D
Cambien
François
F
Kempf
Tibor
T
Wollert
Kai C
KC
Benjamin
Emelia J
EJ
Lackner
Karl J
KJ
Münzel
Thomas F
TF
Tiret
Laurence
L
Vasan
Ramachandran S
RS
Blankenberg
Stefan
S
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
D015415:Biomarkers