Serum osteoprotegerin, sRANKL and carotid plaque formation and growth in a general population--the Tromsø study.
BACKGROUND
Intervention studies in animal models suggest that osteoprotegerin (OPG) functions as an inhibitor or marker of atherosclerosis, whereas one prospective epidemiological study in humans indicated that OPG was an independent risk factor for progression of atherosclerosis.


OBJECTIVE
To study the association between serum levels of OPG, soluble RANK ligand (sRANKL) and carotid artery plaque formation and plaque growth.


METHODS
The prevalence of carotid plaque and plaque area were assessed by ultrasonographic imaging at baseline and after 7 years follow-up in 2191 men and 2329 women who participated in a population-based study.


RESULTS
OPG was significantly associated with atherosclerotic plaque burden and cardiovascular risk factors such as age, body mass index, blood pressure, total cholesterol, HDL cholesterol, HbA1c and fibrinogen at baseline, but not with sRANKL. In subjects without plaque at baseline, OPG predicted plaque formation in crude analysis in both women and men, but not after adjustment for age and other atherosclerotic risk factors. OPG predicted plaque growth in women (+1.8 mm(2), 0.6-3.0) (mean, 95% CI) per 1 SD increase in OPG (P = 0.003), whereas no associations were demonstrated in men (0.1 mm(2) (-1.3-1.4), P = 0.93). Soluble RANKL did not predict plaque formation or plaque growth.


CONCLUSIONS
OPG was an independent predictor of plaque growth in women, but not in men, suggesting gender-specific actions of OPG in plaque growth. OPG was not associated with novel plaque formation.
Vik
A
A
Department of Medicine, Institute of Clinical Medicine, University of Tromsø, Center for Atherothrombotic Research in Tromsø, N-9037 Tromsø, Norway. anders.vik@uit.no
Mathiesen
E B
EB
Johnsen
S H
SH
Brox
J
J
Wilsgaard
T
T
Njølstad
I
I
Hansen
J-B
JB
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood*; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*
D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human