Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome R M Oemrawsingh, 1,2 T Lenderink, 3 K M Akkerhuis, 1 C Heeschen, 4 S Baldus, 5 S Fichtlscherer, 6 C W Hamm, 7 M L Simoons, 1 E Boersma, 1 on behalf of the CAPTURE investigators ABSTRACT Objective To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients 1090 patients with NSTEACS. Main outcome measure All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 mg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 mg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population. Atherosclerosis and plaque destabilisation leading to coronary thrombosis and an acute coronary syndrome (ACS) are the result of a very heteroge- neous process, involving vascular inflammation, endothelial dysfunction and hypercoagulability. 1 Several novel serum biomarkers are thought to reflect these pathophysiological constituents of coronary artery disease (CAD) and have also proved to be independent predictors of future coronary events. C-reactive protein is the most extensively studied biomarker in this respect. It has been shown to be useful not only as a prognostic tool in patients with ACS, 2 but also in predicting the future risk of CAD in apparently healthy men and women. 3 Myeloperoxidase, a leucocytic enzyme that appears as part of the host defence in inflam- matory disorders, and also present in soft plaque, was associated with an increased risk of major adverse cardiac events in patients with documented ACS, 2 as well as in those presenting with chest pain without evidence of myocardial necrosis. 4 Also expressed in ruptured and eroded plaques, but not in stable plaques, is the metalloproteinase preg- nancy-associated plasma protein A (PAPP-A). 5 6 Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, is considered a primary inflammatory instigator in atherosclerotic lesions, 7 and has prognostic value in patients with ACS. 8 In contrast, elevated levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were associated with a lower risk of coro- nary events in patients with ACS and elevated high-sensitivity C-reactive protein (hsCRP) levels, 9 emphasising the importance of an inflammatory balance in the vascular wall. Finally, elevated levels of soluble CD40 ligand (sCD40L), which is primarily released from activated platelets, 10 were associated with an increased cardiovascular risk during 6 months of follow-up of ACS-patients. 11 The prognostic value of these and other biomarkers for the risk of future cardiovascular events in ACS patients has previously been studied. These analyses typically assess each marker individually with adjustment for clinical patient characteristics. In certain cases, two markers are combined in one model. 12 There are only two reports, however, in which the specific combination of three biomarkers provided incremental value for risk prediction after ACS. 13 14 Furthermore, the follow- up duration of previous multimarker studies in ACS patients was often limited to periods consisting of several months up to a maximum of 1 year after admission. 2 5 8 9 11 13e15 Nevertheless, coro- nary pathophysiology is sustained after acute interventional or pharmacological treatment and 1 Thoraxcenter, Department of Cardiology, ErasmusMC and Cardiovascular Research Institute COEUR, Rotterdam, The Netherlands 2 Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands 3 Department of Cardiology, Atrium Medical Centre, Heerlen, The Netherlands 4 Centro Nacional de Investigaciones Oncolo ´gicas (CNIO), Stem Cells & Cancer Group, Madrid, Spain 5 Department of Cardiology, University of Hamburg, Hamburg, Germany 6 Department of Cardiology, JW Goethe University, Frankfurt, Germany 7 Kerckhoff Heart Center, Bad Neuheim, Germany Correspondence to Professor Eric Boersma, Erasmus MC, Thoraxcenter, Department of Cardiology, room Bd381, ’s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; h.boersma@erasmusmc.nl Accepted 1 March 2011 Published Online First 10 May 2011 Heart 2011;97:1061e1066. doi:10.1136/hrt.2010.197392 1061 Acute coronary syndromes group.bmj.com on December 7, 2012 - Published by heart.bmj.com Downloaded from