Abstract 1027: Multiple Biomarkers for Long-Term Risk Stratification in Patients With Coronary Artery Disease
Background-Multiple biomarkers have been suggested for risk prediction in coronary artery disease. Results of single and multimarker approaches have remained inconsistent.
Methods and Results-We prospectively investigated 12 biomarkers reflecting inflammation (C-reactive protein, growth-differentiation factor (GDF)-15, neopterin), oxidative stress (Cu/Zn-superoxiddismutase), lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C), cardiovascular function and remodeling (copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-pro-ANP), and 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 a median follow-up of 3.6 years. Using Cox regression models and C-indices, the strongest association with outcome in the validation set was observed for MR-proADM, cystatin C, GDF-15, Nt-proBNP, and MR-proANP. We developed two risk scores
from forward stepwise variable selection (Nt-proBNP and GDF-15; HR 1.46, 1.12–1.91; C-index 0.73),
through Lasso method (MR-proADM, MR-proANP, neopterin, GDF-15, Nt-proBNP; HR 1.43, 1.11–1.83; C-index 0.73), which performed similar to the top five single markers.
Each top single marker and the scores added incremental predictive information beyond the baseline model (all p<0.0001 by AUC for 3-year survival) and lead to substantial reclassification for prediction ofcardiovascular outcomes.
Conclusions-Comparative analysis of 12 biomarkers revealed MR-proADM, cystatin C, GDF-15, and the natriuretic peptides Nt-proBNP and MR-proANP as the strongest predictors of cardiovascular outcome in stable angina. All five biomarkers offered incremental predictive ability over established risk factors as single markers or incorporated in scores.