Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial.
BACKGROUND
Circulating levels of osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is predictive of death and hospitalization for heart failure after acute coronary syndrome. The association between OPG and outcome in patients with chronic heart failure (CHF) is unknown.


METHODS
Plasma OPG levels at baseline were assessed in 1,229 patients with CHF recruited from 51 clinical centers and included in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) trial. Patients were randomized to n-3 polyunsaturated fatty acids (1 g/d) or rosuvastatin (10 mg/d) versus placebo. Osteoprotegerin was analyzed by enzyme-linked immunosorbent assay. The association between OPG and outcome was assessed by Cox proportional hazards regression models.


RESULTS
During a median follow-up time of 3.9 years, 332 patients died; and 791 patients died or were hospitalized because of cardiovascular causes. By univariate analysis, baseline OPG levels were strongly associated with the incidence of death (hazard ratio {HR} [95% CI] 1.53 [1.40-1.67] per 1-SD increase in log OPG). After adjustment for conventional risk markers, OPG remained a significant predictor of death (HR [95% CI] 1.20 [1.06-1.35], P < .001). Similar findings were observed for the composite end point (HR [95% CI] 1.34 [1.07-1.69], P = .012).


CONCLUSIONS
In patients with CHF, OPG is associated with the incidence of death independently of conventional cardiovascular risk factors.
Røysland
Ragnhild
R
Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
Masson
Serge
S
Omland
Torbjørn
T
Milani
Valentina
V
Bjerre
Mette
M
Flyvbjerg
Allan
A
Di Tano
Giuseppe
G
Misuraca
Gianfranco
G
Maggioni
Aldo P
AP
Tognoni
Gianni
G
Tavazzi
Luigi
L
Latini
Roberto
R
D000368:Aged; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D015200:Fluoroimmunoassay; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007558:Italy; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin; D011379:Prognosis; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053244:Osteoprotegerin; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium