title: Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP.
abstract: OBJECTIVE
  To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP).
  
  
  METHODS
  OPG and hsCRP concentrations were measured at baseline in a large Danish prospective community-based population study.
  
  
  METHODS
  The 4th Copenhagen City Heart Study.
  
  
  METHODS
  5863 men and women aged 20-95 were recruited from the general population.
  
  
  METHODS
  Combined end-point of IHD, ischaemic stroke or all-cause mortality.
  
  
  RESULTS
  During a median follow-up of 7.8 years (IQR 7.3-8.3), 1270 subjects (21.7%) reached the combined end-point. A twofold increase in plasma OPG was a significant predictor of the combined end-point (univariable HR 1.85, 95% CI 1.75 to 1.96; p<0.001). In a multivariable Cox-regression model containing age, male sex, hypertension, diabetes, hypercholesterolaemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischaemic stroke, hsCRP and plasma OPG, high concentrations of hsCRP and plasma OPG were independent predictors of the combined end-point. The two biomarkers interacted statistically (p<0.001). Compared to low hsCRP and low OPG (n=1927), either high hsCRP or high OPG (univariable HR 2.38, 95% CI 2.02 to 2.80, p<0.001; n=2816), or both high hsCRP and high OPG (univariable HR 5.13, 95% CI 4.29 to 6.13, p<0.001; n=775) conferred increased risk of the combined end-point.
  
  
  CONCLUSIONS
  OPG is an independent predictor of the combined end-point of hospitalisation of IHD, ischaemic stroke and all-cause mortality. The combination of plasma OPG and hsCRP provides more prognostic information than the individual effect of the two biomarkers.
authors.affiliation: Department of Cardiology, University of Copenhagen, 2.14.1, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark. Rasmus.Mogelvang@get2net.dk
authors.forename: Rasmus
authors.initials: R
authors.lastname: Mogelvang
authors.forename: Sune
authors.initials: S
authors.lastname: Haahr-Pedersen
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Allan
authors.initials: A
authors.lastname: Iversen
authors.forename: Søren
authors.initials: S
authors.lastname: Galatius
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D002423:Cause of Death / Q000639:trends; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011159:Population Surveillance; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D002097:C-Reactive Protein