Coronary artery disease| Volume 111, ISSUE 9, P1237-1245, May 01, 2013

Association Among Leukocyte Count, Mortality, and Bleeding in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes (from the Acute Catheterization and Urgent Intervention Triage StrategY [ACUITY] Trial)

Published:February 13, 2013DOI:
      Although inflammation is involved in the pathogenesis of acute coronary syndromes, the extent of inflammation is not routinely assessed, and its prognostic implications in patients with non–ST-segment elevation acute coronary syndrome have not been investigated in depth. We analyzed the prognostic implications of an elevated white blood cell count (WBCc) in patients with moderate and high-risk non–ST-segment elevation acute coronary syndrome undergoing an early invasive strategy in the large-scale Acute Catheterization and Urgent Intervention Triage StrategY trial. The WBCc at admission was available for 13,678 of 13,819 patients (98.9%). The patients in the upper tertile of the WBCc had an increased risk of 30-day major bleeding, 1-year mortality, and definite/probable stent thrombosis compared to those in the mid or lower tertiles. On multivariate analysis, the WBCc was an independent predictor of 30-day major bleeding and 1-year cardiac, noncardiac, and all-cause mortality. The association between the WBCc and cardiac mortality was present in multiple prespecified subgroups, with no significant interaction between the WBCc and age, gender, diabetes, smoking, renal dysfunction, elevated baseline biomarkers, antithrombotic therapy, revascularization, and Thrombolysis In Myocardial Infarction risk score. The WBCc remained an independent predictor of mortality after adjusting for bleeding, C-reactive protein level, and angiographic variables, including left ventricular ejection fraction, Thrombolysis In Myocardial Infarction flow, and number of diseased vessels. The WBCc significantly improved the prognostic accuracy of the Thrombolysis In Myocardial Infarction risk score, with a net reclassification improvement of 11% (p <0.0001). In conclusion, in patients with moderate- and high-risk non–ST-segment elevation acute coronary syndrome, an elevated admission WBCc was an independent predictor of 30-day major bleeding, and 1-year cardiac, noncardiac, and all-cause mortality.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Rangel-Frausto M.S.
        • Pittet D.
        • Costigan M.
        • Hwang T.
        • Davis C.S.
        • Wenzel R.P.
        The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study.
        JAMA. 1995; 273: 117-123
        • Bhatt D.L.
        • Chew D.P.
        • Lincoff A.M.
        • Simoons M.L.
        • Harrington R.A.
        • Ommen S.R.
        • Jia G.
        • Topol E.J.
        Effect of revascularization on mortality associated with an elevated white blood cell count in acute coronary syndromes.
        Am J Cardiol. 2003; 92: 136-140
        • Furman M.I.
        • Gore J.M.
        • Anderson F.A.
        • Budaj A.
        • Goodman S.G.
        • Avezum A.
        • Lopez-Sendon J.
        • Klein W.
        • Mukherjee D.
        • Eagle K.A.
        • Dabbous O.H.
        • Goldberg R.J.
        Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE).
        Am Heart J. 2004; 147: 42-48
        • Mueller C.
        • Neumann F.J.
        • Perruchoud A.P.
        • Buettner H.J.
        White blood cell count and long term mortality after non-ST elevation acute coronary syndrome treated with very early revascularisation.
        Heart. 2003; 89: 389-392
        • Sabatine M.S.
        • Morrow D.A.
        • Cannon C.P.
        • Murphy S.A.
        • Demopoulos L.A.
        • DiBattiste P.M.
        • McCabe C.H.
        • Braunwald E.
        • Gibson C.M.
        Relationship between baseline white blood cell count and degree of coronary artery disease and mortality in patients with acute coronary syndromes: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction 18 trial) substudy.
        J Am Coll Cardiol. 2002; 40: 1761-1768
        • Stone G.W.
        • Bertrand M.
        • Colombo A.
        • Dangas G.
        • Farkouh M.E.
        • Feit F.
        • Lansky A.J.
        • Lincoff A.M.
        • Mehran R.
        • Moses J.W.
        • Ohman M.
        • White H.D.
        Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial: study design and rationale.
        Am Heart J. 2004; 148: 764-775
        • Cutlip D.E.
        • Windecker S.
        • Mehran R.
        • Boam A.
        • Cohen D.J.
        • van Es G.A.
        • Steg P.G.
        • Morel M.A.
        • Mauri L.
        • Vranckx P.
        • McFadden E.
        • Lansky A.
        • Hamon M.
        • Krucoff M.W.
        • Serruys P.W.
        Clinical end points in coronary stent trials: a case for standardized definitions.
        Circulation. 2007; 115: 2344-2351
        • Aoki J.
        • Lansky A.J.
        • Mehran R.
        • Moses J.
        • Bertrand M.E.
        • McLaurin B.T.
        • Cox D.A.
        • Lincoff A.M.
        • Ohman E.M.
        • White H.D.
        • Parise H.
        • Leon M.B.
        • Stone G.W.
        Early stent thrombosis in patients with acute coronary syndromes treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage Strategy trial.
        Circulation. 2009; 119: 687-698
        • Karabinos I.
        • Koulouris S.
        • Kranidis A.
        • Pastromas S.
        • Exadaktylos N.
        • Kalofoutis A.
        Neutrophil count on admission predicts major in-hospital events in patients with a non–ST-segment elevation acute coronary syndrome.
        Clin Cardiol. 2009; 32: 561-568
        • Huang G.
        • Zhong X.N.
        • Zhong B.
        • Chen Y.Q.
        • Liu Z.Z.
        • Su L.
        • Ling Z.Y.
        • Cao H.
        • Yin Y.H.
        Significance of white blood cell count and its subtypes in patients with acute coronary syndrome.
        Eur J Clin Invest. 2009; 39: 348-358
        • Ndrepepa G.
        • Braun S.
        • Iijima R.
        • Keta D.
        • Byrne R.A.
        • Schulz S.
        • Mehilli J.
        • Schomig A.
        • Kastrati A.
        Total leukocyte count, but not C-reactive protein, predicts 1-year mortality in patients with acute coronary syndromes treated with percutaneous coronary intervention.
        Clin Sci (Lond). 2009; 116: 651-658
        • Palmerini T.
        • Mehran R.
        • Dangas G.
        • Nikolsky E.
        • Witzenbichler B.
        • Guagliumi G.
        • Dudek D.
        • Genereux P.
        • Caixeta A.
        • Rabbani L.
        • Weisz G.
        • Parise H.
        • Fahy M.
        • Xu K.
        • Brodie B.
        • Lansky A.
        • Stone G.W.
        Impact of leukocyte count on mortality and bleeding in patients with myocardial infarction undergoing primary percutaneous coronary interventions: analysis from the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction trial.
        Circulation. 2011; 123: 2829-2837
        • Grzybowski M.
        • Welch R.D.
        • Parsons L.
        • Ndumele C.E.
        • Chen E.
        • Zalenski R.
        • Barron H.V.
        The association between white blood cell count and acute myocardial infarction in-hospital mortality: findings from the National Registry of Myocardial Infarction.
        Acad Emerg Med. 2004; 11: 1049-1060
        • Hochholzer W.
        • Wiviott S.D.
        • Antman E.M.
        • Contant C.F.
        • Guo J.
        • Giugliano R.P.
        • Dalby A.J.
        • Montalescot G.
        • Braunwald E.
        Predictors of bleeding and time dependence of association of bleeding with mortality: insights from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38).
        Circulation. 2011; 123: 2681-2689
        • Suh J.W.
        • Mehran R.
        • Claessen B.E.
        • Xu K.
        • Baber U.
        • Dangas G.
        • Parise H.
        • Lansky A.J.
        • Witzenbichler B.
        • Grines C.L.
        • Guagliumi G.
        • Kornowski R.
        • Wohrle J.
        • Dudek D.
        • Weisz G.
        • Stone G.W.
        Impact of in-hospital major bleeding on late clinical outcomes after primary percutaneous coronary intervention in acute myocardial infarction the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial.
        J Am Coll Cardiol. 2011; 58: 1750-1756
        • Coller B.S.
        Leukocytosis and ischemic vascular disease morbidity and mortality: is it time to intervene?.
        Arterioscler Thromb Vasc Biol. 2005; 25: 658-670
        • Palmerini T.
        • Coller B.S.
        • Cervi V.
        • Tomasi L.
        • Marzocchi A.
        • Marrozzini C.
        • Leone O.
        • Piccioli M.
        • Branzi A.
        Monocyte-derived tissue factor contributes to stent thrombosis in an in vitro system.
        J Am Coll Cardiol. 2004; 44: 1570-1577
        • Palmerini T.
        • Nedelman M.A.
        • Scudder L.E.
        • Nakada M.T.
        • Jordan R.E.
        • Smyth S.
        • Gordon R.E.
        • Fallon J.T.
        • Coller B.S.
        Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates.
        J Am Coll Cardiol. 2002; 40: 360-366
        • Goel M.S.
        • Diamond S.L.
        Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and -independent mechanisms.
        Arterioscler Thromb Vasc Biol. 2001; 21: 2093-2098
        • Mickelson J.K.
        • Lakkis N.M.
        • Villarreal-Levy G.
        • Hughes B.J.
        • Smith C.W.
        Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease?.
        J Am Coll Cardiol. 1996; 28: 345-353
        • Meisel S.R.
        • Shapiro H.
        • Radnay J.
        • Neuman Y.
        • Khaskia A.R.
        • Gruener N.
        • Pauzner H.
        • David D.
        Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.
        J Am Coll Cardiol. 1998; 31: 120-125
        • Becker L.B.
        New concepts in reactive oxygen species and cardiovascular reperfusion physiology.
        Cardiovasc Res. 2004; 61: 461-470
        • Zhang R.
        • Brennan M.L.
        • Fu X.
        • Aviles R.J.
        • Pearce G.L.
        • Penn M.S.
        • Topol E.J.
        • Sprecher D.L.
        • Hazen S.L.
        Association between myeloperoxidase levels and risk of coronary artery disease.
        JAMA. 2001; 286: 2136-2142
        • Sharma R.
        • Anker S.D.
        Immune and neurohormonal pathways in chronic heart failure.
        Congest Heart Fail. 2002; 8: 23-28
        • Tamhane U.U.
        • Aneja S.
        • Montgomery D.
        • Rogers E.K.
        • Eagle K.A.
        • Gurm H.S.
        Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome.
        Am J Cardiol. 2008; 102: 653-657