Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial

Am Heart J. 2010 Aug;160(2):286-93. doi: 10.1016/j.ahj.2010.05.015.


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).

Conclusion: In patients with CHF, OPG is associated with the incidence of death independently of conventional cardiovascular risk factors.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Female
  • Fluorobenzenes / therapeutic use
  • Fluoroimmunoassay
  • Heart Failure / blood*
  • Heart Failure / drug therapy
  • Heart Failure / mortality*
  • Hospitalization / statistics & numerical data
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Italy
  • Male
  • Middle Aged
  • Osteoprotegerin
  • Prognosis
  • Proportional Hazards Models
  • Pyrimidines / therapeutic use
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use


  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Osteoprotegerin
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium