Serum levels of soluble receptor activator for nuclear factor kB ligand play a crucial role in the association of osteoprotegerin with coronary artery disease.

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor kB ligand (RANKL), and is implicated in the pathogenesis of atherosclerosis. The aim of the present study was to examine the hypothesis that serum OPG concentrations are increased in patients with stable coronary artery disease (CAD) at different serum levels of soluble RANKL (sRANKL). The study used a case-control design in which consecutively hospitalized individuals were recruited. Fasting blood samples were taken upon admission for serum testing. Participants with previously diagnosed CAD that was asymptomatic or had controlled symptoms constituted the stable CAD group, whereas patients with negative coronary computed tomography angiography results constituted the control non-CAD group. Exclusion criteria included recent acute coronary syndrome, severe heart failure, CAD-complicating autoimmune, blood or thyroid diseases, cancer, elevated temperature with or without infection, severe liver or kidney dysfunction, abnormal calcium metabolism, recent surgery and trauma history. A total of 118 individuals were included in the study. Smoothed plots generated using the recursive method and multivariate models showed that the incidence of stable CAD increased with serum OPG level up to the turning point of 18 pg/ml. This trend was observed at both high [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.04-2.50; P=0.032) and low sRANKL concentrations (OR, 1.52; 95% CI, 1.06-2.17; P=0.022) after adjustment for cardiovascular risk factors. In conclusion, serum OPG levels ≤18 pg/ml are positively associated with stable CAD, regardless of sRANKL levels. In addition, at the same serum OPG level, higher sRANKL levels are associated with a greater incidence of stable CAD compared with lower sRANKL levels. This study identified the relationship between OPG, sRANKL, and stable CAD, and established the reference range for future clinical use.