Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease

  • Stefan Kiechl
    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.
  • Georg Schett
    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.
  • Gregor Wenning
    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.
  • Kurt Redlich
    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.
  • Martin Oberhollenzer
    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.
  • Agnes Mayr
    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.
  • Peter Santer
    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.
  • Josef Smolen
    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.
  • Werner Poewe
    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.
  • Johann Willeit
    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.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-κB ligand. Recent experimental research has implicated osteoprotegerin in atherogenesis, but epidemiological confirmation of this concept is sparse. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> 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]; <jats:italic>P</jats:italic> =0.001) and vascular mortality (adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [1.2 to 8.2]; <jats:italic>P</jats:italic> =0.010) but not for mortality due to nonvascular causes. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease. </jats:p>

収録刊行物

  • Circulation

    Circulation 109 (18), 2175-2180, 2004-05-11

    Ovid Technologies (Wolters Kluwer Health)

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