The long pentraxin 3 (PTX3): a novel prognostic inflammatory marker for mortality in acute chest pain

Summary

The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in several conditions including acute coronary syndromes (ACS). The aim of this study was to assess the value of PTX3 as a prognostic marker of mortality and recurrent ischaemic events in a consecutive series of patients admitted with acute chest pain and potential ACS.

The patients received follow-up for 24 months. Blood samples were taken on admission for measurement of PTX3, high sensitive C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), and troponin T. All-cause mortality at 24 months in the study cohort was 15.2%. Patients in the upper PTX3 quartiles had a significantly higher death risk than those in the lowest quartile (Q3: hazard ratio [HR] 2.36; 95% CI 1.12–4.99; p=0.024, and Q4: HR 3.60; 95% CI 1.68–7.72; p=0.001). Elevated BNP levels were also significantly associated with a fatal outcome (Q3: HR 3.05; 95% CI 1.16–7.99; p=0.024; and Q4: HR 3.90; 95% CI 1.48–10.26; p=0.006). Elevation in hsCRP was not associated with increased death risk. As PTX3 predicted mortality independently of BNP, the combination of these two biomarkers showed an incremental prognostic value.

PTX3 is a new biomarker related to inflammation that, independently of BNP, strongly predicts long-term all-cause mortality in patients with acute chest pain. The combination of these two biomarkers enhances the prognostic value over either marker alone.

Keywords

PTX3 - chest pain - prognosis - clinical studies - atherothrombosis - inflammation

^* Current affiliation: Novartis Pharma K.K., Tokyo, Japan

• References

• 1 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
• 2 Garlanda C, Bottazzi B, Bastone A. et al. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 2005; 23: 337-366.
• 3 Alles VV, Bottazzi B, Peri G. et al. Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes. Blood 1994; 84: 3483-3493.
• 4 Klouche M, Peri G, Knabbe C. et al. Modified atherogenic lipoproteins induce expression of pentraxin-3 by human vascular smooth muscle cells. Atherosclerosis 2004; 175: 221-228.
• 5 Rolph MS, Zimmer S, Bottazzi B. et al. Production of the long pentraxin PTX3 in advanced atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2002; 22: e10-e14.
• 6 Inoue K, Sugiyama A, Reid PC. et al. Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris. Arterioscler Thromb Vasc Biol 2007; 27: 161-167.
• 7 Latini R, Maggioni AP, Peri G. et al. Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation 2004; 110: 2349-2354.
• 8 Peri G, Introna M, Corradi D. et al. PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000; 102: 636-641.
• 9 Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in “active” coronary artery disease. Am J Cardiol 1990; 65: 168-172.
• 10 Liuzzo G, Biasucci LM, Gallimore JR. 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.
• 11 Richards AM, Nicholls MG, Espiner EA. et al. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation 2003; 107: 2786-2792.
• 12 Kim H, Yang DH, Park Y. et al. Incremental prognostic value of C-reactive protein and N-terminal proBtype natriuretic peptide in acute coronary syndrome. Circ J 2006; 70: 1379-1384.
• 13 Bogaty P, Boyer L, Simard S. et al. Clinical utility of C-reactive protein measured at admission, hospital discharge, and 1 month later to predict outcome in patients with acute coronary disease. The RISCA (recurrence and inflammation in the acute coronary syndromes) study. J Am Coll Cardiol 2008; 51: 2339-2346.
• 14 Wollert KC, Kempf T, Peter T. et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation 2007; 115: 962-971.
• 15 Brugger-Andersen T, Ponitz V, Staines H. et al. The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain. Blood Coagul Fibrinolysis 2008; 19: 701-707.
• 16 Muller-Bardorff M, Hallermayer K, Schroder A. et al. Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation. Clin Chem 1997; 43: 458-466.
• 17 Lee GW, Lee TH, Vilcek J. TSG-14, a tumor necrosis factor and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. J Immunol 1993; 150: 1804-1812.
• 18 Lee GW, Goodman AR, Lee TH. et al. Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins. J Immunol 1994; 153: 3700-3707.
• 19 de Lemos JA, Morrow DA, Bentley JH. et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001; 345: 1014-1021.
• 20 Morrow DA, de Lemos JA, Sabatine MS. et al. Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol 2003; 41: 1264-1272.
• 21 Omland T, Persson A, Ng L. et al. N-terminal pro- B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation 2002; 106: 2913-2918.
• 22 Montalescot G, Dallongeville J, Van BE. et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J 2007; 28: 1409-1417.