Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction.
OBJECTIVE
Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI.


RESULTS
This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT.


CONCLUSIONS
Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI.


BACKGROUND
ClinicalTrials.gov, NCT00470587.
Department of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Willibald
W
Hochholzer
Tobias
T
Reichlin
Claudia
C
Stelzig
Kirsten
K
Hochholzer
Julia
J
Meissner
Tobias
T
Breidthardt
Miriam
M
Reiter
Bettina
B
Duehsler
Heike
H
Freidank
Katrin
K
Winkler
Raphael
R
Twerenbold
Christian
C
Mueller
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D042241:Early Diagnosis; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1