Document Detail

Soluble receptor activator of nuclear factor-kappa B ligand and risk for cardiovascular disease.
MedLine Citation:
PMID:  17620507     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Overexpression of receptor activator of nuclear factor-kappaB ligand (RANKL) is a prominent feature of vulnerable atherosclerotic lesions prone to rupture and was thought to contribute to the transition from a stable to an unstable plaque phenotype in both human and murine atherosclerosis because of its ability to promote matrix degradation, monocyte/macrophage chemotaxis, and vascular calcification. METHODS AND RESULTS: The Bruneck Study is a prospective, population-based survey of men and women 40 to 79 years of age at the 1990 baseline examination. Levels of soluble RANKL and other variables were assessed in 909 subjects (1990). All cases of cardiovascular disease were carefully recorded between 1990 and 2005. During follow-up, cardiovascular disease (defined as ischemic stroke and transient ischemic attack, myocardial infarction, and vascular death) manifested in 124 of the 909 subjects. Baseline serum level of RANKL emerged as a highly significant predictor of vascular risk (adjusted hazard ratio per 1-unit increase in soluble RANKL, 1.27; 95% confidence interval, 1.16 to 1.40; P<0.001). Predictive significance was independent of that afforded by the classic vascular risk factors, C-reactive protein, osteoprotegerin concentration, and severity of carotid atherosclerosis. Findings were internally consistent and robust in a variety of sensitivity analyses. Notably, soluble RANKL was not associated with carotid or femoral artery atherosclerosis. CONCLUSIONS: Our study lends large-scale epidemiological support to a role for RANKL in cardiovascular disease. In the absence of a significant association between RANKL and atherosclerosis, the idea that RANKL promotes plaque destabilization and rupture is a highly appealing concept.
Stefan Kiechl; Georg Schett; Judith Schwaiger; Klaus Seppi; Paula Eder; Georg Egger; Peter Santer; Agnes Mayr; Qingbo Xu; Johann Willeit
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-09
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-24     Completed Date:  2007-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  385-91     Citation Subset:  AIM; IM    
Department of Neurology, Innsbruck Medical University, Anichstr 35, A-6020 Innsbruck, Austria.
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MeSH Terms
Biological Markers / blood
Cardiovascular Diseases / blood*,  epidemiology*
Cohort Studies
Follow-Up Studies
Middle Aged
Prospective Studies
RANK Ligand / blood*
Risk Factors
Reg. No./Substance:
0/Biological Markers; 0/RANK Ligand

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