Elevated placental growth factor levels are associated with adverse outcomes at four-year follow-up in patients with acute coronary syndromes.
OBJECTIVE
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.
Lenderink
Timo
T
Department of Cardiology, Atrium Medical Centre, Heerlen, The Netherlands. t.lenderink@atriummc.nl
Heeschen
Christopher
C
Fichtlscherer
Stephan
S
Dimmeler
Stefanie
S
Hamm
Christian W
CW
Zeiher
Andreas M
AM
Simoons
Maarten L
ML
Boersma
Eric
E
D000077284:Abciximab; D000789:Angina, Unstable / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D023201:CD40 Ligand / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood*; D000072483:Placenta Growth Factor; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D011257:Pregnancy Proteins / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D020107:Troponin T / Q000097:blood
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D006133:Growth Substances; D007140:Immunoglobulin Fab Fragments; C000608036:PGF protein, human; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011257:Pregnancy Proteins; D020107:Troponin T; D000072483:Placenta Growth Factor; D023201:CD40 Ligand; D002097:C-Reactive Protein; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D000077284:Abciximab