Prognostic value of apoptosis markers in advanced heart failure patients.
OBJECTIVE
Apoptosis plays an important role in the progression of heart failure (HF). The purpose of this study was to assess whether the pro-apoptotic molecules apoptosis-stimulating fragment (FAS, CD95/APO-1) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) predict event-free survival of HF patients.


RESULTS
We assayed soluble (s)FAS and sTRAIL levels in 351 patients with advanced HF. During the median follow-up time of 16 months, 175 patients (50%) experienced the composite endpoints: rehospitalization and death. The hazard increased with sFAS concentrations, with a hazard ratio of 2.3 comparing fourth and first quartiles. This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = 0.014). Patients with high sFAS but low BNP had a comparable event-free survival rate with those with elevated BNP only (P = 0.78). Conversely, high sTRAIL concentrations were related to a better prognosis. Particularly, the risk of mortality dropped by 70% in the fourth quartile of sTRAIL (P = 0.001, multivariable Cox regression model).


CONCLUSIONS
sFAS is an independent risk predictor in advanced HF patients. It may be of particular value for the identification of high-risk patients in addition to BNP. Conversely, sTRAIL appears to be protective and could be an interesting therapeutic agent.
Niessner
Alexander
A
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Hohensinner
Philipp J
PJ
Rychli
Kathrin
K
Neuhold
Stephanie
S
Zorn
Gerlinde
G
Richter
Bernhard
B
Hülsmann
Martin
M
Berger
Rudolf
R
Mörtl
Deddo
D
Huber
Kurt
K
Wojta
Johann
J
Pacher
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019014:fas Receptor; D020097:Natriuretic Peptide, Brain