Serum osteoprotegerin, sRANKL and carotid plaque formation and growth in a general population--the Tromsø study

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.

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

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.

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.

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.