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CLINICAL RESEARCH: ACUTE CORONARY SYNDROME

Elevated Placental Growth Factor Levels Are Associated With Adverse Outcomes at Four-Year Follow-Up in Patients With Acute Coronary Syndromes

Timo Lenderink, MD^_*,,_*, Christopher Heeschen, MD, Stephan Fichtlscherer, MD, Stefanie Dimmeler, MD, Christian W. Hamm, MD^||, Andreas M. Zeiher, MD, Maarten L. Simoons, MD^_*, Eric Boersma, PhD^_* for the CAPTURE Investigators

^_* Department of Cardiology, Atrium Medical Centre, Heerlen, the Netherlands
Department of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
Department of Surgery, Ludwig-Maximilians-University, Munich, Germany
Department of Cardiology, J. W. Goethe University, Frankfurt, Germany
^|| Department of Cardiology, Kerckhoff Heart Center, Bad Neuheim, Germany

Manuscript received April 10, 2005; revised manuscript received July 7, 2005, accepted August 9, 2005.

^_* Reprint requests and correspondence: Dr. Timo Lenderink, Department of Cardiology, Atrium Medical Centre Heerlen, H. Dunantstr. 5, 6419 PC Heerlen, the Netherlands. (Email: t.lenderink{at}atriummc.nl).

OBJECTIVES: This study sought to evaluate the predictive value of baseline placental growth factor (PlGF) for long-term cardiovascular events in acute coronary syndromes (ACS).

BACKGROUND: A biomarker of vascular inflammation, PlGF is identified as a powerful predictor for short-term outcome in patients with ACS.

METHODS: In 544 patients who were enrolled in the placebo arm of the c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina (CAPTURE) trial, PlGF levels were determined as well as markers of myocardial necrosis (troponin T [TnT]), general inflammation (high-sensitivity C-reactive protein [hsCRP]), and platelet activation (soluble CD40 ligand [sCD40L]). Cox proportional hazard regression analyses were applied to evaluate the relationship between biomarkers and the occurrence of all-cause death or non-fatal myocardial infarction during a median follow-up period of four years.

RESULTS: Patients with PlGF levels in the fourth and fifth quintile (>27 ng/l) had higher mortality than those with lower levels (10.8% vs. 3.2%; hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6 to 7.1), as well as a higher incidence of the composite end point of death or myocardial infarction (27.6% vs. 11.3% events; HR, 2.6; 95% CI, 1.7 to 3.9). The relationship between PlGF and the composite end point remained significant after adjustment for TnT, sCD40L, and hsCRP (adjusted HR, 3.3; 95% CI, 2.0 to 5.4).

CONCLUSIONS: In patients with ACS, elevated plasma levels of PlGF are associated with adverse cardiac outcomes during long-term follow-up. These data suggest that PlGF as a more specific marker of vascular inflammation should be considered for risk stratification of patients with ACS rather than general markers of inflammation.

Abbreviations and Acronyms   ACS = acute coronary syndrome   hsCRP = high-sensitivity C-reactive protein   PlGF = placental growth factor   sCD40L = soluble CD40 ligand   TnT = troponin T

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