Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease

Circulation. 2004 May 11;109(18):2175-80. doi: 10.1161/01.CIR.0000127957.43874.BB. Epub 2004 Apr 26.


Background: Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-kappaB ligand. Recent experimental research has implicated osteoprotegerin in atherogenesis, but epidemiological confirmation of this concept is sparse.

Methods and results: As part of the prospective, population-based Bruneck Study, severity, initiation, and progression of atherosclerosis were assessed in carotid arteries. Cases of incident cardiovascular disease and vascular mortality were carefully recorded over a 10-year period (1990 to 2000). Osteoprotegerin levels were measured in samples obtained at baseline and during follow-up. Serum osteoprotegerin showed a strong association with numerous vascular risk factors, including age, diabetes, markers of systemic inflammation, chronic infection, and smoking. In multivariate analyses, osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis. Furthermore, a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [1.3 to 3.8]; P=0.001) and vascular mortality (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [1.2 to 8.2]; P=0.010) but not for mortality due to nonvascular causes.

Conclusions: Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers
  • Calcinosis / epidemiology
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / epidemiology
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / epidemiology
  • Cohort Studies
  • Comorbidity
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Humans
  • Incidence
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Osteoprotegerin
  • Prospective Studies
  • Receptors, Cytoplasmic and Nuclear / blood*
  • Receptors, Tumor Necrosis Factor
  • Risk
  • Risk Factors
  • Sampling Studies
  • Ultrasonography
  • Vascular Diseases / mortality


  • Biomarkers
  • Glycoproteins
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human