TY - JOUR
T1 - Multiple marker approach to risk stratification in patients with stable coronary artery disease
AU - Schnabel, Renate B.
AU - Schulz, Andreas
AU - Messow, C. Martina
AU - Lubos, Edith
AU - Wild, Philipp S.
AU - Zeller, Tanja
AU - Sinning, Christoph R.
AU - Rupprecht, Hans J.
AU - Bickel, Christoph
AU - Peetz, Dirk
AU - Cambien, François
AU - Kempf, Tibor
AU - Wollert, Kai C.
AU - Benjamin, Emelia J.
AU - Lackner, Karl J.
AU - Münzel, Thomas F.
AU - Tiret, Laurence
AU - Vasan, Ramachandran S.
AU - Blankenberg, Stefan
N1 - Funding Information:
The AtheroGene study is supported by a grant of the ‘Stiftung Rheinland-Pfalz für Innovation,’ Ministry for Science and Education (AZ 15202–386261/545), Mainz; R.S. is funded by a German Research Foundation Research Fellowship SCHN 1149/1-1. This work was further supported by research grants from the Brandenburg Ministry of Economics, Germany, and the European Regional Development Fund (EFRE/ERDF).
PY - 2010/12
Y1 - 2010/12
N2 - Aims 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. Methods and 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). Conclusion 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.
AB - Aims 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. Methods and 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). Conclusion 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.
KW - Cohort study
KW - Coronary artery disease
KW - Multiple biomarkers
KW - Reclassification
KW - Risk stratification
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U2 - 10.1093/eurheartj/ehq322
DO - 10.1093/eurheartj/ehq322
M3 - Article
C2 - 20852293
AN - SCOPUS:78650367767
SN - 0195-668X
VL - 31
SP - 3024
EP - 3031
JO - European Heart Journal
JF - European Heart Journal
IS - 24
ER -