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Proteomics and Protein Markers |
1 Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, University of Minnesota School of Medicine, Minneapolis, MN.
2 Biostatistical Consulting, Minot, ND.
aAddress correspondence to this author at: Hennepin County Medical Center, Clinical Labs P4, 701 Park Ave., Minneapolis, MN 55415. Fax 612-904-4229; e-mail apple004{at}umn.edu.
Background: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome.
Methods: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan–Meier method and relative risk (RR) with the Cox proportional hazards model.
Results: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P 
0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%.
Conclusion: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome.
The following articles in journals at HighWire Press have cited this article:
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  S. Giovannini, G. Onder, C. Leeuwenburgh, C. Carter, E. Marzetti, A. Russo, E. Capoluongo, M. Pahor, R. Bernabei, and F. Landi Myeloperoxidase Levels and Mortality in Frail Community-Living Elderly Individuals J Gerontol A Biol Sci Med Sci, January 11, 2010; (2010) glp183v1. [Abstract] [Full Text] [PDF]
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 M. Markovic, S. Ignjatovic, N. Majkic-Singh, and M. Dajak Placental Growth Factor in Acute Coronary Syndrome Patients with Non ST-Elevation Lab Med, November 1, 2009; 40(11): 675 - 678. [Abstract] [Full Text] [PDF]
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 C. Antoniades, C. Bakogiannis, D. Tousoulis, A. S. Antonopoulos, and C. Stefanadis The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J. Am. Coll. Cardiol., August 18, 2009; 54(8): 669 - 677. [Abstract] [Full Text] [PDF]
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 R. K. Schindhelm, L. P. van der Zwan, T. Teerlink, and P. G. Scheffer Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification? Clin. Chem., August 1, 2009; 55(8): 1462 - 1470. [Abstract] [Full Text] [PDF]
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F. S. Apple, S. W. Smith, L. A. Pearce, and M. M. Murakami Assessment of the Multiple-Biomarker Approach for Diagnosis of Myocardial Infarction in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome Clin. Chem., January 1, 2009; 55(1): 93 - 100. [Abstract] [Full Text] [PDF]
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J. Shih, S. A. Datwyler, S. C. Hsu, M. S. Matias, D. P. Pacenti, C. Lueders, C. Mueller, O. Danne, and M. Mockel Effect of Collection Tube Type and Preanalytical Handling on Myeloperoxidase Concentrations Clin. Chem., June 1, 2008; 54(6): 1076 - 1079. [Abstract] [Full Text] [PDF]
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 D. A. Morrow, M. S. Sabatine, M.-L. Brennan, J. A. de Lemos, S. A. Murphy, C. T. Ruff, N. Rifai, C. P. Cannon, and S. L. Hazen Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18 Eur. Heart J., May 1, 2008; 29(9): 1096 - 1102. [Abstract] [Full Text] [PDF]
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M. Weber and C. Hamm Novel biomarkers--the long march from bench to bedside Eur. Heart J., May 1, 2008; 29(9): 1079 - 1081. [Full Text] [PDF]
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