Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease.
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.


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.
Kiechl
Stefan
S
Department of Neurology, University Clinic, Anichstrasse 35, A-6020 Innsbruck, Austria. Stefan.Kiechl@uibk.ac.at
Schett
Georg
G
Wenning
Gregor
G
Redlich
Kurt
K
Oberhollenzer
Martin
M
Mayr
Agnes
A
Santer
Peter
P
Smolen
Josef
J
Poewe
Werner
W
Willeit
Johann
J
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers; D002114:Calcinosis / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D053244:Osteoprotegerin; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012306:Risk; D012307:Risk Factors; D012494:Sampling Studies; D014463:Ultrasonography; D014652:Vascular Diseases / Q000401:mortality
D015415:Biomarkers; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human