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

• Published in: European heart journal 2011-02, Vol.32 (3), p.326-335
• Main Authors: HOCHHOLZER, Willibald, REICHLIN, Tobias, TWERENBOLD, Raphael, MUELLER, Christian, STELZIG, Claudia, HOCHHOLZER, Kirsten, MEISSNER, Julia, BREIDTHARDT, Tobias, REITER, Miriam, DUEHSLER, Bettina, FREIDANK, Heike, WINKLER, Katrin
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - metabolism; Cardiology. Vascular system; Coronary heart disease; Early Diagnosis; Heart; Humans; Medical sciences; Middle Aged; Myocardial Infarction - diagnosis; Myocarditis. Cardiomyopathies; Placenta Growth Factor; Pregnancy Proteins - metabolism; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Young Adult
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehq429

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. 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. 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. ClinicalTrials.gov, NCT00470587.