Multiple biomarker use for detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome.
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 < or = 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%.


CONCLUSIONS
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.
Apple
Fred S
FS
Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, University of Minnesota School of Medicine, Minneapolis, MN, USA. apple004@umn.edu
Pearce
Lesly A
LA
Chung
Adrine
A
Ler
Ranka
R
Murakami
MaryAnn M
MM
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D023381:Endpoint Determination; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D013577:Syndrome
D015415:Biomarkers