We evaluated the ability of 8 biomarkers representing distinct pathophysiological pathways related to cardiovascular events in coronary artery disease.Methods:
We measured 8 biomarkers representing inflammation (growth differentiation factor-15 [GDF-15], fibrinogen), renal function (creatinine), endothelial activation (uric acid [UA]), cardiovascular stress (N-terminal-pro-B-type natriuretic peptide [NT-proBNP], soluble ST2 [sST2]), plaque instability (pregnancy-associated plasma protein A [PAPP-A]), and activated coagulation (D-dimer) in 3440 patients with coronary artery disease and assessed their association with myocardial infarction, stroke, cardiovascular death, heart failure and all cause death (clinical events, n = 419) over 2.9 years.Results:
The strongest association with outcome in multivariable-adjusted analyses was observed for NT-proBNP (hazard ratio [HR] for one standard deviation [SD] increase 1.67, 95% confidence interval [CI] 1.55–1.8, C-index 0.824), GDF-15 (HR 1.74, 95% CI 1.52–2, C-index 0.806), fibrinogen (HR 3.83, 95% CI 2.66–5.52, C-index 0.798), UA (HR 2.7, 95% CI 1.92–3.8, C-index 0.792), D-dimer (HR 1.51, 95% CI 1.37–1.67, C-index 0.8) and creatinine (HR 2.51, 95% CI 2.1–3.01, C-index 0.8). Each of these single markers and their combination (C-index 0.835) added predictive information beyond that obtained by baseline model and led to substantial reclassification (P-integrated discrimination improvement < 0.05).Conclusion:
NT-proBNP, GDF-15, fibrinogen, UA, D-dimer, and creatinine are complementary prognostic biomarkers. Combination of the single markers significantly enhanced risk prediction but slightly improved the model fit. Mutimarker approach may improve identification of high-risk patients with CAD in need of more aggressive therapeutic interventions.