Prognostic significance of angiogenic growth factor serum levels in patients with acute coronary syndromes.
BACKGROUND
In patients with acute coronary syndromes, compensatory processes are initiated, including angiogenesis and endothelial regeneration of ruptured or eroded plaques. Angiogenic growth factors like vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and basic fibroblast growth factor (bFGF) are upregulated during ischemia. However, it is unknown whether their serum levels are related to clinical outcome.


RESULTS
We measured VEGF, HGF, and bFGF levels in 1090 patients with acute coronary syndromes. Angiographic evaluation was performed at baseline as well as death, and nonfatal myocardial infarctions were recorded during 6-month follow-up. HGF and VEGF, but not bFGF, were significantly and independently associated with the patients' outcome. Patients with elevated VEGF serum levels suffered from adverse outcome (adjusted hazard ratio, 2.50 [1.52 to 4.82]; P=0.002). VEGF elevation was associated with evidence of ischemia and was a significant predictor of the effect of glycoprotein IIb/IIIa inhibition. In contrast, patients with high HGF levels had a significantly lower event rate compared with patients with low HGF levels (adjusted hazard ratio, 0.33 [0.21 to 0.51]; P<0.001). HGF levels did not correlate with evidence of ischemia and did not predict the effect of abciximab. Intriguingly, however, HGF levels significantly correlated with angiographically visible collateralization of the target vessel (22.4% versus 10.5%; P<0.001).


CONCLUSIONS
The angiogenic growth factors VEGF and HGF are independent predictors of the patients' prognosis in acute coronary syndromes. Whereas VEGF elevation correlated with the evidence of myocardial ischemia and indicated an adverse outcome, HGF elevation was independent of ischemia and associated with improved collateralization as well as a favorable prognosis.
Heeschen
Christopher
C
Department of Internal Medicine IV, Molecular Cardiology, University of Frankfurt, Germany. c.heeschen@em.uni-frankfurt.de
Dimmeler
Stefanie
S
Hamm
Christian W
CW
Boersma
Eric
E
Zeiher
Andreas M
AM
Simoons
Maarten L
ML
D000077284:Abciximab; D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016228:Endothelial Growth Factors; D007140:Immunoglobulin Fab Fragments; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D000077284:Abciximab