Prognostic value of pigment epithelium-derived factor in patients with advanced heart failure.
OBJECTIVE
Whereas angiogenesis, the formation of new blood vessels from preexisting vessels, may be beneficial in restoring failing myocardium, apoptosis may contribute to the progression of heart failure (HF). We investigated the role of pigment epithelium-derived factor (PEDF), a recently discovered antiangiogenic factor with additional proapoptotic effects, in patients with advanced HF.


METHODS
We assayed PEDF levels in 351 patients with advanced HF at baseline. During the median follow-up time of 16 months, 50% of patients experienced the composite end point of rehospitalization and/or death.


RESULTS
The risk of a clinical event increased with concentrations of the antiangiogenic marker PEDF, with a 1.94-fold higher risk in the third tertile compared with the first tertile (95% CI, 1.33-2.84). This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = .015). Experimental data revealed that PEDF may contribute to the progression of HF by inducing apoptosis in human cardiac myocytes and fibroblasts via activation of caspase 3.


CONCLUSIONS
We suggest a role of PEDF in the progression of HF by inducing apoptosis of human cardiac myocytes and fibroblasts. Our clinical data suggest that PEDF concentrations may have the potential to become a valuable marker of the prognosis of HF, in addition to BNP.
Rychli
Kathrin
K
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Niessner
Alexander
A
Hohensinner
Philipp J
PJ
Mahdy Ali
Kariem
K
Kaun
Christoph
C
Neuhold
Stephanie
S
Zorn
Gerlinde
G
Richter
Bernhard
B
Hülsmann
Martin
M
Berger
Rudolf
R
Mörtl
Deddo
D
Huber
Kurt
K
Maurer
Gerald
G
Pacher
Richard
R
Wojta
Johann
J
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018572:Disease-Free Survival; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D015843:Serpins / Q000097:blood*; D015996:Survival Rate; D000099174:Pigment Epithelium-Derived Factor
D015415:Biomarkers; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor