Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.
BACKGROUND
Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown.


RESULTS
MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 microg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P=0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 microg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P=0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P=0.023), C-reactive protein (1.25; P=0.044), vascular endothelial growth factor (HR 1.87; P=0.041), soluble CD40 ligand (HR 2.78; P<0.001), and MPO (HR 2.11; P=0.008) were all independent predictors of the patient's 6-month outcome.


CONCLUSIONS
In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS.
Baldus
Stephan
S
University of Hamburg, Department of Cardiology, Martinistrasse 52, 20246 Hamburg, Germany. baldus@uke.uni-hamburg.de
Heeschen
Christopher
C
Meinertz
Thomas
T
Zeiher
Andreas M
AM
Eiserich
Jason P
JP
Münzel
Thomas
T
Simoons
Maarten L
ML
Hamm
Christian W
CW
D000077284:Abciximab; D000208:Acute Disease; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000097:blood*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D018570:Risk Assessment
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007140:Immunoglobulin Fab Fragments; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D009195:Peroxidase; D000077284:Abciximab