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CLINICAL RESEARCH: BIOMARKERS

Prognostic Value of Biomarkers During and After Non–ST-Segment Elevation Acute Coronary Syndrome

Kai M. Eggers, MD, PhD^_*,_*, Bo Lagerqvist, MD, PhD^_*, Per Venge, MD, PhD, Lars Wallentin, MD, PhD^_* and Bertil Lindahl, MD, PhD^_*

^_* Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Centre, Uppsala, Sweden
Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, Uppsala, Sweden

Manuscript received October 20, 2008; revised manuscript received January 30, 2009, accepted March 10, 2009.

^_* Reprint requests and correspondence: Dr. Kai M. Eggers, Department of Medical Sciences, Cardiology, University Hospital Uppsala, S-751 85 Uppsala, Sweden (Email: kai.eggers{at}ucr.uu.se).

Objectives: The aim of this study was to assess risk prediction by different biomarkers in patients with an ongoing non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and after clinical stabilization.

Background: Different biomarkers reflect different aspects of the pathobiology in NSTE-ACS. However, there is little information regarding their relative prognostic value during the time course of disease.

Methods: The N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), cardiac troponin I (cTnI), and the estimated glomerular filtration rate (eGFR) were measured at randomization and after 6 weeks and 6 months in 877 NSTE-ACS patients included in the FRISC (FRagmin and fast revascularization during InStability in Coronary artery disease) II trial. The biomarkers' prognostic value during 5-year follow-up was evaluated by Cox regression models, calculation of the c-statistics, and estimation of the net reclassification improvement (NRI).

Results: Among the biomarkers measured at randomization, NT-proBNP was the strongest predictor for mortality (adjusted hazard ratio [HR]: 1.7; 95% confidence interval [CI]: 1.3 to 2.1; p < 0.001). Even during follow-up, NT-proBNP demonstrated the strongest association to the composite end point of death/myocardial infarction (adjusted HR at 6 weeks: 1.5; 95% CI: 1.3 to 1.7; p < 0.001; adjusted HR at 6 months: 1.4; 95% CI: 1.2 to 1.7; p = 0.001). Even CRP was independently predictive at 6 months for the composite end point (adjusted HR: 1.3; 95% CI: 1.1 to 1.5; p = 0.003). Only 6-week results of NT-proBNP provided significant incremental prognostic value to established risk indicators regarding the composite end point (c-statistics 0.69 [p = 0.03]; NRI 0.11 [p = 0.03]).

Conclusions: The NT-proBNP is an independent risk predictor in patients with ongoing NSTE-ACS and after clinical stabilization. The CRP exhibits increasing predictive value at later measurements. However, only NT-proBNP provided incremental prognostic value and might therefore be considered as a complement for early follow-up controls after NSTE-ACS.

Key Words: acute coronary syndrome • biomarkers • risk assessment • stable coronary artery disease

Abbreviations and Acronyms   AMI = acute myocardial infarction   CRP = C-reactive protein   cTnI = cardiac troponin I   eGFR = estimated glomerular filtration rate   NRI = net reclassification improvement   NSTE-ACS = non–ST-segment elevation acute coronary syndrome   NT-proBNP = N-terminal pro-brain natriuretic peptide

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