on January 20, 2003
Published online before print January 20, 2003, doi: 10.1161/01.CIR.0000048183.37648.1A
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 30, 2002
From the Department of Internal Medicine IV (C.H., S.D., A.M.Z.), Molecular Cardiology, University of Frankfurt, Germany; the Erasmus University Hospital (E.B., M.L.S.), Thoraxcentre, Rotterdam, the Netherlands; and the Kerckhoff Heart Center (C.W.H.), Department of Cardiology, Bad Nauheim, Germany. * To whom correspondence should be addressed. E-mail: c.heeschen{at}em.uni-frankfurt.de.
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. Methods and 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.
Revised on October 17, 2002
Accepted on October 20, 2002
Prognostic Significance of Angiogenic Growth Factor Serum Levels in Patients With Acute Coronary Syndromes
Christopher Heeschen MD*,
Key words: angina • angiogenesis • prognosis
This article has been cited by other articles:
 |
|
 |
|
  F. H. Seeger, T. Rasper, M. Koyanagi, H. Fox, A. M. Zeiher, and S. Dimmeler CXCR4 Expression Determines Functional Activity of Bone Marrow-Derived Mononuclear Cells for Therapeutic Neovascularization in Acute Ischemia Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1802 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gupta, J. Tongers, and D. W. Losordo Human Studies of Angiogenic Gene Therapy Circ. Res., October 9, 2009; 105(8): 724 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tello-Montoliu, F. Marin, J. Patel, V. Roldan, L. Mainar, V. Vicente, F. Sogorb, and G. Y.H. Lip Plasma angiogenin levels in acute coronary syndromes: implications for prognosis Eur. Heart J., December 2, 2007; 28(24): 3006 - 3011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Imagawa, S. Fujii, J. Dong, T. Furumoto, T. Kaneko, T. Zaman, Y. Satoh, H. Tsutsui, and B. E Sobel Hepatocyte Growth Factor Regulates E Box-Dependent Plasminogen Activator Inhibitor Type 1 Gene Expression in HepG2 Liver Cells Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2407 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kodama, Y. Kitta, T. Nakamura, H. Takano, K. Umetani, D. Fujioka, Y. Saito, K.-i. Kawabata, J.-e. Obata, A. Mende, et al. Atorvastatin Increases Plasma Soluble Fms-Like Tyrosine Kinase-1 and Decreases Vascular Endothelial Growth Factor and Placental Growth Factor in Association With Improvement of Ventricular Function in Acute Myocardial Infarction J. Am. Coll. Cardiol., July 4, 2006; 48(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Armstrong, D. A. Morrow, and M. S. Sabatine Inflammatory Biomarkers in Acute Coronary Syndromes: Part III: Biomarkers of Oxidative Stress and Angiogenic Growth Factors Circulation, February 28, 2006; 113(8): e289 - e292. [Full Text] [PDF]
|
|
|
|
|
|
S. Susen, K. Sautiere, F. Mouquet, F. Cuilleret, A. Chmait, E. P. McFadden, B. Hennache, F. Richard, P. de Groote, J.-M. Lablanche, et al. Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization Eur. Heart J., November 2, 2005; 26(22): 2387 - 2395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Heeschen, S. Dimmeler, C. W. Hamm, S. Fichtlscherer, M. L. Simoons, A. M. Zeiher, and CAPTURE Study Investigators Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis J. Am. Coll. Cardiol., January 18, 2005; 45(2): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Lim, A. D. Blann, A. Y. Chong, B. Freestone, and G. Y.H. Lip Plasma Vascular Endothelial Growth Factor, Angiopoietin-1, and Angiopoietin-2 in Diabetes: Implications for cardiovascular risk and effects of multifactorial intervention Diabetes Care, December 1, 2004; 27(12): 2918 - 2924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wojakowski, M. Tendera, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, R. Wyderka, A. Ochala, and M. Z. Ratajczak Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ Stem Cells, and Mononuclear Cells Expressing Early Cardiac, Muscle, and Endothelial Markers Into Peripheral Blood in Patients With Acute Myocardial Infarction Circulation, November 16, 2004; 110(20): 3213 - 3220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Lee, G. Y.H. Lip, and A. D. Blann Plasma Angiopoietin-1, Angiopoietin-2, Angiopoietin Receptor Tie-2, and Vascular Endothelial Growth Factor Levels in Acute Coronary Syndromes Circulation, October 19, 2004; 110(16): 2355 - 2360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Werner, E. Jandt, A. Krack, G. Schwarz, O. Mutschke, F. Kuethe, M. Ferrari, and H. R. Figulla Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions: Relation to Duration of Occlusion and Collateral Function Circulation, October 5, 2004; 110(14): 1940 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D Blann Angiogenesis and platelets: the clot thickens further Cardiovasc Res, August 1, 2004; 63(2): 192 - 193. [Full Text] [PDF]
|
|
|
|
|
|
P. Porcu, C. Emanueli, E. Desortes, G. M. Marongiu, F. Piredda, L. Chao, J. Chao, and P. Madeddu Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1104 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Heeschen, S. Dimmeler, S. Fichtlscherer, C. W. Hamm, J. Berger, M. L. Simoons, and A. M. Zeiher Prognostic Value of Placental Growth Factor in Patients With Acute Chest Pain JAMA, January 28, 2004; 291(4): 435 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Baldus, C. Heeschen, T. Meinertz, A. M. Zeiher, J. P. Eiserich, T. Munzel, M. L. Simoons, C. W. Hamm, and on behalf of the CAPTURE Investigators Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes Circulation, September 23, 2003; 108(12): 1440 - 1445. [Abstract] [Full Text] [PDF]
|
|