Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality.
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.
Lieb
Wolfgang
W
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass,. USA.
Gona
Philimon
P
Larson
Martin G
MG
Massaro
Joseph M
JM
Lipinska
Izabella
I
Keaney
John F
JF
Rong
Jian
J
Corey
Diane
D
Hoffmann
Udo
U
Fox
Caroline S
CS
Vasan
Ramachandran S
RS
Benjamin
Emelia J
EJ
O'Donnell
Christopher J
CJ
Kathiresan
Sekar
S
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
D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
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