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Canadian Journal of Cardiology

A Risk Assessment Tool Incorporating New Biomarkers for Cardiovascular Events in Acute Coronary Syndromes: The Organization to Assess Strategies in Ischemic Syndromes (OASIS) Risk Score

Published:February 02, 2016DOI:https://doi.org/10.1016/j.cjca.2016.01.029

      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.

      Résumé

      Introduction

      Il a été démontré que divers biomarqueurs permettent d’améliorer la stratification du risque chez les patients présentant un syndrome coronarien aigu sans sus-décalage du segment ST (SCA ST-), mais ces données n’ont pas encore été intégrées aux outils d’évaluation du risque.

      Méthodes

      Les taux de protéine C-réactive, de fraction N-terminale du propeptide natriurétique de type B (NT-proBNP pour N-terminal-pro–brain natriuretic peptide) et d’hémoglobine glyquée (HbA1c) ont été mesurés chez 6447 patients atteints d’un SCA ST- inscrits à l’étude Clopidogrel in Unstable Angina to Prevent Recurrent Events. Un score de risque permettant de prédire la probabilité de décès de cause cardiovasculaire (CV), d’infarctus du myocarde (IM) ou d’accident vasculaire cérébral (AVC) à 1 an a été établi en incorporant les biomarqueurs permettant de prédire de manière indépendante la survenue d’un événement aux critères de risque connus, soit l’électrocardiogramme et le taux de troponine T. L’approche discriminative a été évaluée à l’aide de l’aire sous la courbe ROC (Receiver Operating Characteristic [fonction d’efficacité du récepteur]), de l’indice IDI (Integrated Discrimination Improvement Index [indice d’amélioration de discrimination intégrée]) et de l’indice NRI (Net Reclassification Index [indice d’amélioration de reclassement net]). Cette approche a ensuite été validée à l’aide des méthodes d’autoamorçage (bootstrap).

      Résultats

      Au cours de la période de suivi de 1 an, 686 patients ont connu un événement CV. Chacun des biomarqueurs a permis de prédire le décès de cause CV, l’IM ou l’AVC, mais seulement la NT-proBNP et l’HbA1c ont permis d’améliorer l’approche discriminative en augmentant respectivement l’aire sous la courbe ROC (de 0,66 à 0,71), l’IDI à 3,4 % et le NRI à 17,5 % (p < 0,0001 pour l’ensemble des mesures). Une échelle de risque variant de 0 à 20 points a été mise au point en fonction des variables suivantes : âge, IM ou AVC antérieur, sexe, déviation du segment ST, taux de troponine T, taux de NT-proBNP et taux d’HbA1c. À l’aide de cette échelle, les patients ont été classés à faible risque, à risque intermédiaire ou à risque élevé de décès de cause CV, d’IM ou d’AVC selon une proportion de 3,7, 9,1 et 17,8 %, respectivement. Le bienfait absolu d’une bithérapie antiplaquettaire par rapport à l’aspirine seule a pour sa part été estimé à 1,0, 4,7 et 3,0 % respectivement parmi les patients à faible risque, à risque intermédiaire ou à risque élevé d’événement CV.

      Conclusions

      En ajoutant les taux de NT-proBNP et d’HbA1c aux 5 variables traditionnelles, on a obtenu une échelle de risque en 7 points qui permet de mieux prédire la survenue d’un événement CV à 1 an et qui facilite la sélection liée au risque des patients présentant un SCA ST- susceptibles de bénéficier d’une bithérapie antiplaquettaire.
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      References

        • Fox K.A.
        • Steg P.G.
        • Eagle K.A.
        • et al.
        • GRACE Investigators
        Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006.
        JAMA. 2007; 297: 1892-1900
        • Amsterdam E.A.
        • Wenger N.K.
        • Brindis R.G.
        • et al.
        AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 64: e139-e228
        • Roffi M.
        • Patrono C.
        • Collet J.-P.
        • et al.
        2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).
        Eur Heart J. 2016; 37: 267-315
        • Tanguay J.-F.
        • Bell A.D.
        • Ackman M.L.
        • et al.
        Focused 2012 update of the Canadian Cardiovascular Society guidelines for the use of antiplatelet therapy.
        Can J Cardiol. 2013; 29: 1334-1345
        • Eagle K.A.
        • Lim M.J.
        • Dabbous O.H.
        • et al.
        A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry.
        JAMA. 2004; 291: 2727-2733
        • Fox K.A.
        • Dabbous O.H.
        • Goldberg R.J.
        • et al.
        Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
        BMJ. 2006; 333: 1091
        • Granger C.B.
        • Goldberg R.J.
        • Dabbous O.
        • et al.
        Predictors of hospital mortality in the global registry of acute coronary events.
        Arch Intern Med. 2003; 63: 2345-2353
        • Fox K.A.A.
        • FitzGerald G.
        • Puymirat E.
        • et al.
        Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score.
        BMJ Open. 2014; 4: e004425
        • Antman E.M.
        • Cohen M.
        • Bernink P.J.
        • et al.
        The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making.
        JAMA. 2000; 284: 835-842
        • Lindahl B.
        • Toss H.
        • Siegbahn A.
        • Venge P.
        • Wallentin L.
        Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in coronary artery disease.
        N Engl J Med. 2000; 343: 1139-1147
        • Liuzzo G.
        • Biasucci L.M.
        • Gallimore J.R.
        • et al.
        The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.
        N Engl J Med. 1994; 331: 417-424
        • James S.K.
        • Lindahl B.
        • Siegbahn A.
        • et al.
        N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy.
        Circulation. 2003; 108: 275-281
        • Giraldez R.R.
        • Clare R.M.
        • Lopes R.D.
        • et al.
        Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non-ST-segment elevation acute coronary syndrome.
        Am Heart J. 2013; 165: 918-925
        • Sabatine M.S.
        • Morrow D.A.
        • de Lemos J.A.
        • et al.
        Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease.
        Circulation. 2012; 125: 233-240
        • Zethelius B.
        • Berglund L.
        • Sundström J.
        • et al.
        Use of multiple biomarkers to improve the prediction of death from cardiovascular causes.
        N Engl J Med. 2008; 358: 2107-2116
        • Scirica B.M.
        • Sabatine M.S.
        • Jarolim P.
        • et al.
        Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.
        Eur Heart J. 2011; 32: 697-705
        • Morrow D.A.
        • Cannon C.P.
        • Jesse R.L.
        • et al.
        National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes.
        Circulation. 2007; 115: e356-e375
        • Yusuf S.
        • Zhao F.
        • Mehta S.R.
        • et al.
        Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.
        N Engl J Med. 2001; 345: 494-502
        • Sullivan L.M.
        • Massaro J.M.
        • D'Agostino Sr., R.B.
        Presentation of multivariate data for clinical use: the Framingham study risk score functions.
        Stat Med. 2004; 23: 1631-1660
        • Pencina M.J.
        • D'Agostino Sr., R.B.
        • Steyerberg E.W.
        Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.
        Stat Med. 2011; 30: 11-21
        • Austin P.C.
        • Tu J.V.
        Bootstrapping methods for developing predictive models.
        Am Stat. 2004; 58: 131-137
        • Mehta S.R.
        • Granger C.B.
        • Boden W.E.
        • et al.
        Early versus delayed invasive intervention in acute coronary syndromes.
        N Engl J Med. 2009; 360: 2165-2175
        • Eggers K.M.
        • Lagerqvist B.
        • Venge P.
        • Wallentin L.
        • Lindahl B.
        Prognostic value of biomarkers during and after non-ST-segment elevation acute coronary syndrome.
        J Am Coll Cardiol. 2009; 54: 357-364
        • Wallentin L.
        • Becker R.C.
        • Budaj A.
        • et al.
        Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
        N Engl J Med. 2009; 361: 1045-1057
        • Wiviott S.D.
        • Braunwald E.
        • McCabe C.H.
        • et al.
        Prasugrel versus clopidogrel in patients with acute coronary syndromes.
        N Engl J Med. 2007; 357: 2001-2015