Shamir R Mehta1, John W Eikelboom2, Purnima Rao-Melacini2, Jeffrey I Weitz3, Sonia S Anand2, Guillaume Pare2, Andrezj Budaj4, Janice Pogue2, Keith A A Fox5, Salim Yusuf2. 1. Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address: smehta@mcmaster.ca. 2. Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. 3. Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. 4. Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland. 5. Royal Infirmary, University of Edinburgh, Edinburgh, Scotland.
Abstract
BACKGROUND: Several biomarkers have been shown to improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS); however, they have not been integrated into risk prediction tools. METHODS: C-reactive-protein, N-terminal-pro-brain natriuretic peptide (NT-proBNP), and haemoglobin A1C were measured in 6447 patients with NSTEACS who were enrolled in the Clopidogrel in Unstable Angina to Prevent Recurrent Events trial. A risk score to predict cardiovascular (CV) death, myocardial infarction (MI), or stroke at 1 year was developed by incorporating biomarkers that were independently predictive of events with traditional variables, electrocardiogram, and troponin-T. Model discrimination was evaluated using c-statistic, integrated discrimination improvement, and net reclassification index, and validated using bootstrap methods. RESULTS: During 1 year of follow-up, 686 patients experienced a CV event. Each biomarker predicted CV death, MI, or stroke; however, only NT-proBNP and haemoglobin A1C improved model discrimination, increasing the c-statistic (0.66-0.71), integrated discrimination improvement to 3.4%, and net reclassification index to 17.5% (P < 0.0001 for all measures). A risk score ranging from 0 to 20 points including variables for age, prior MI/stroke, sex, ST-segment deviation, troponin-T, NT-proBNP, and haemoglobin A1C classified individuals into low-, intermediate-, and high-risk groups with rates of CV death, MI, stroke of 3.7%, 9.1%, 17.8%, respectively. The absolute benefit of dual antiplatelet therapy vs aspirin alone was 1.0%, 4.7%, and 3.0% in low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: The addition of NT-proBNP and haemoglobin A1C to 5 standard variables creates a 7-variable risk score that improves prediction of CV events at 1 year and aids in risk-based selection of patients with NSTEACS for dual antiplatelet therapy.
BACKGROUND: Several biomarkers have been shown to improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS); however, they have not been integrated into risk prediction tools. METHODS: C-reactive-protein, N-terminal-pro-brain natriuretic peptide (NT-proBNP), and haemoglobin A1C were measured in 6447 patients with NSTEACS who were enrolled in the Clopidogrel in Unstable Angina to Prevent Recurrent Events trial. A risk score to predict cardiovascular (CV) death, myocardial infarction (MI), or stroke at 1 year was developed by incorporating biomarkers that were independently predictive of events with traditional variables, electrocardiogram, and troponin-T. Model discrimination was evaluated using c-statistic, integrated discrimination improvement, and net reclassification index, and validated using bootstrap methods. RESULTS: During 1 year of follow-up, 686 patients experienced a CV event. Each biomarker predicted CV death, MI, or stroke; however, only NT-proBNP and haemoglobin A1C improved model discrimination, increasing the c-statistic (0.66-0.71), integrated discrimination improvement to 3.4%, and net reclassification index to 17.5% (P < 0.0001 for all measures). A risk score ranging from 0 to 20 points including variables for age, prior MI/stroke, sex, ST-segment deviation, troponin-T, NT-proBNP, and haemoglobin A1C classified individuals into low-, intermediate-, and high-risk groups with rates of CV death, MI, stroke of 3.7%, 9.1%, 17.8%, respectively. The absolute benefit of dual antiplatelet therapy vs aspirin alone was 1.0%, 4.7%, and 3.0% in low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: The addition of NT-proBNP and haemoglobin A1C to 5 standard variables creates a 7-variable risk score that improves prediction of CV events at 1 year and aids in risk-based selection of patients with NSTEACS for dual antiplatelet therapy.