Circulation. 2004;109:2175-2180
Published online before print April 26, 2004, doi: 10.1161/01.CIR.0000127957.43874.BB
Published online before print April 26, 2004, doi: 10.1161/01.CIR.0000127957.43874.BB
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(Circulation. 2004;109:2175-2180.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease
From the Department of Neurology (S.K., G.W., W.P., J.W.), Innsbruck University Clinic, Innsbruck, Austria; Division of Rheumatology (G.S., K.R., J.S.), Department of Internal Medicine III, University of Vienna, Vienna, Austria; and Departments of Internal Medicine (M.O.) and Laboratory Medicine (A.M., P.S.), Bruneck Hospital, Bruneck, Italy.
Correspondence to Dr S. Kiechl, Department of Neurology, University Clinic, Anichstraße 35, A-6020 Innsbruck, Austria. E-mail Stefan.Kiechl{at}uibk.ac.at
Received August 4, 2003; de novo received October 14, 2003; revision received December 11, 2003; accepted February 13, 2004.
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-
B 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.
Key Words: atherosclerosis • risk factors • myocardial infarction • inflammation • immune system
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