title: Osteoprotegerin predicts progression of chronic heart failure: results from CORONA.
abstract: BACKGROUND
  Osteoprotegerin (OPG) may be implicated in the pathogenesis of heart failure (HF), and circulating levels predict survival in patients with postinfarction HF. Our primary goal was to determine whether OPG provided independent prognostic information in patients with chronic HF, and to examine its potential interactions with statin therapy.
  
  
  RESULTS
  OPG as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke; n=318), all-cause mortality (n=329), and all-cause mortality/hospitalization for worsening of heart failure (WHF; n=475) was investigated in 1464 patients (≥60 years, New York Heart Association class II to IV, ischemic systolic HF, optimal pharmacological therapy) in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, randomly assigned to 10 mg rosuvastatin or placebo. In multivariate analyses, OPG (continuous variable) added no significant predictive information for risk estimation of the primary end point (adjusting for left ventricular ejection fraction, New York Heart Association class, age, body mass index, diabetes, sex, intermittent claudication, heart rate, serum creatinine, apoA1, and N-terminal pro-B-type natriuretic peptide). However, OPG added independent predictive information for WHF hospitalization (hazard ratio [HR] 1.10 [1.04 to 1.16], P<0.001) and all-cause mortality/WHF hospitalization (HR 1.06 [1.01 to 1.11]). The HR indicated a reduced risk for all-cause mortality in the rosuvastatin group in those with lowest OPG values (tertile 1, HR=0.66 unadjusted [P=0.025]; HR=0.71 Cox adjusted [P=0.025]; interaction by treatment effect for the tertiles P=0.086).
  
  
  CONCLUSIONS
  OPG added no predictive information for the primary end point, but independently predicted WHF hospitalization in older patients with advanced chronic systolic HF of ischemic etiology. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. thor.ueland@medisin.uio.no
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Johannes
authors.initials: J
authors.lastname: Hulthe
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Assen
authors.initials: A
authors.lastname: Goudev
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindberg
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005060:Europe; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D053244:Osteoprotegerin; D011743:Pyrimidines; D013449:Sulfonamides; C506030:TNFRSF11B protein, human; D000068718:Rosuvastatin Calcium