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Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis.
J Am Coll Cardiol 2005; 45(2):229-37JACC

Abstract

OBJECTIVES

The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A (PAPP-A) in patients with acute coronary syndromes (ACS).

BACKGROUND

Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization.

METHODS

In 547 patients with angiographically validated ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain, respectively, PAPP-A as well as markers of myocardial necrosis (troponin T [TnT]), ischemia (vascular endothelial growth factor [VEGF]), inflammation (high-sensitivity C-reactive protein [hsCRP]), anti-inflammatory activity (interleukin [IL]-10), and platelet activation (soluble CD40 ligand [sCD40L]) were determined. Patients were followed for the occurrence of death or myocardial infarction.

RESULTS

In patients with ACS, elevated PAPP-A levels (>12.6 mIU/l) indicated an increased risk (odds ratio 2.44 [95% confidence interval (CI) 1.43 to 4.15]; p = 0.001). When the analysis was restricted to TnT-negative patients, PAPP-A still identified a subgroup of high-risk patients (odds ratio [OR] 2.72 [95% confidence interval (CI) 1.25 to 5.89]; p = 0.009). In a multivariable model, PAPP-A (OR 2.01; p = 0.015), sCD40L (OR 2.37; p = 0.003), IL-10 (OR 0.43; p = 0.003), and VEGF (OR 2.19; p = 0.018) were independent predictors. Prospective validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients (adjusted OR 2.32 [95% CI 1.32 to 4.26]; p = 0.008). Patients negative for all three markers (TnT, sCD40L, and PAPP-A) were at very low cardiac risk (30 days: 3.0% event rate; no death).

CONCLUSIONS

The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS. Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS.

Authors+Show Affiliations

Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. c.heeschen@em.uni-frankfurt.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15653020

Citation

Heeschen, Christopher, et al. "Pregnancy-associated Plasma protein-A Levels in Patients With Acute Coronary Syndromes: Comparison With Markers of Systemic Inflammation, Platelet Activation, and Myocardial Necrosis." Journal of the American College of Cardiology, vol. 45, no. 2, 2005, pp. 229-37.
Heeschen C, Dimmeler S, Hamm CW, et al. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J Am Coll Cardiol. 2005;45(2):229-37.
Heeschen, C., Dimmeler, S., Hamm, C. W., Fichtlscherer, S., Simoons, M. L., & Zeiher, A. M. (2005). Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. Journal of the American College of Cardiology, 45(2), pp. 229-37.
Heeschen C, et al. Pregnancy-associated Plasma protein-A Levels in Patients With Acute Coronary Syndromes: Comparison With Markers of Systemic Inflammation, Platelet Activation, and Myocardial Necrosis. J Am Coll Cardiol. 2005 Jan 18;45(2):229-37. PubMed PMID: 15653020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. AU - Heeschen,Christopher, AU - Dimmeler,Stefanie, AU - Hamm,Christian W, AU - Fichtlscherer,Stephan, AU - Simoons,Maarten L, AU - Zeiher,Andreas M, AU - ,, PY - 2004/07/09/received PY - 2004/09/27/accepted PY - 2005/1/18/pubmed PY - 2005/2/23/medline PY - 2005/1/18/entrez SP - 229 EP - 37 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 45 IS - 2 N2 - OBJECTIVES: The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A (PAPP-A) in patients with acute coronary syndromes (ACS). BACKGROUND: Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization. METHODS: In 547 patients with angiographically validated ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain, respectively, PAPP-A as well as markers of myocardial necrosis (troponin T [TnT]), ischemia (vascular endothelial growth factor [VEGF]), inflammation (high-sensitivity C-reactive protein [hsCRP]), anti-inflammatory activity (interleukin [IL]-10), and platelet activation (soluble CD40 ligand [sCD40L]) were determined. Patients were followed for the occurrence of death or myocardial infarction. RESULTS: In patients with ACS, elevated PAPP-A levels (>12.6 mIU/l) indicated an increased risk (odds ratio 2.44 [95% confidence interval (CI) 1.43 to 4.15]; p = 0.001). When the analysis was restricted to TnT-negative patients, PAPP-A still identified a subgroup of high-risk patients (odds ratio [OR] 2.72 [95% confidence interval (CI) 1.25 to 5.89]; p = 0.009). In a multivariable model, PAPP-A (OR 2.01; p = 0.015), sCD40L (OR 2.37; p = 0.003), IL-10 (OR 0.43; p = 0.003), and VEGF (OR 2.19; p = 0.018) were independent predictors. Prospective validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients (adjusted OR 2.32 [95% CI 1.32 to 4.26]; p = 0.008). Patients negative for all three markers (TnT, sCD40L, and PAPP-A) were at very low cardiac risk (30 days: 3.0% event rate; no death). CONCLUSIONS: The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS. Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/15653020/Pregnancy_associated_plasma_protein_A_levels_in_patients_with_acute_coronary_syndromes:_comparison_with_markers_of_systemic_inflammation_platelet_activation_and_myocardial_necrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(04)02039-X DB - PRIME DP - Unbound Medicine ER -