title: Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality.
abstract: OBJECTIVE
  Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD).
  
  
  RESULTS
  Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61+/-9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality.
  
  
  CONCLUSIONS
  Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass,. USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Philimon
authors.initials: P
authors.lastname: Gona
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Izabella
authors.initials: I
authors.lastname: Lipinska
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.forename: Diane
authors.initials: D
authors.lastname: Corey
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood / Q000000981:diagnostic imaging; D002318:Cardiovascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
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